BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans ; Small Cell Lung Carcinoma/therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Antibodies, Monoclonal/therapeutic use* ; Adult ; Immunotherapy/methods* ; Aged, 80 and over

Objective:To analyze the changes of fasting plasma glucose(FPG)level before and after menopause.Methods:Kailuan health checkup cohort was used to extract data of women aged≥18 years who participated in the first physical examination of Kailuan physical examination cohort and had menopausal age at the end of the seventh physical examination. A total of 3 749 women with 22 057 physical examination records were included in the analysis. Natural logarithmic transformation was applied to FPG, and a segmented linear mixed-effects model was used to analyze the changes in ln-transformed FPG before and after menopause. Additionally, an interaction analysis was performed to assess the multiplicative effect of baseline age and baseline body mass index(BMI)on ln-transformed FPG concerning pre- and post-menopausal periods.Results:The average age of the first physical examination for women in this study was (45.63±4.52)years, the median menopausal age was 51(50~53)years, and the median number of physical examinations was 6(5~7)times. The results of the piecewise linear mixed effect model showed that lnFPG increased from 1 year before menopause, with an average annual increase of 0.021 mmol/L, and continued to increase from menopause to 5 years after menopause, with an average annual increase of 0.007 mmol/L. LnFPG tended to be stable after 5 years of menopause. Baseline age could affect the changes of lnFPG before and after menopause, and there was a negative multiplicative interaction between baseline age ≥45 years and the time period from 6 years to 1 year before menopause( P=0.032). Women with baseline age ≥45 years had a higher average annual increase in lnFPG from 1 year before menopause to 5 years after menopause than women with baseline age <45 years( P<0.05). On lnFPG, there was a positive multiplicative interaction between baseline BMI and time segments around menopause. Compared to women with BMI <24.0 kg/m 2, obese women displayed more annual increase in lnFPG from 6 years to 1 year before menopause as well as from menopause to 5 years after menopause( P<0.05). Conclusions:Menopause has an adverse impact on FPG, with the most significant changes occurring within the period of one year before menopause and up to five years after menopause. Age and BMI significantly influence the changes in FPG before and after menopause.

Small for gestational age (SGA) infants are more likely to experience neurocognitive impairments compared to appropriate for gestational age (AGA) infants. This paper reviews recent research on the neurocognitive development of SGA children. SGA can lead to a "brain-sparing effect" due to growth restriction, which may affect cerebral blood flow and brain structure. However, this does not guarantee normal brain development. Restrictive blood flow can result in changes in brain structure, such as reduced total white matter and gray matter volume in various brain regions, including the cerebral cortex, hippocampus and cerebellum, ultimately leading to decreased head circumference. SGA children also exhibit lower scores in all neurocognitive domains, including intelligence, attention, memory, and executive function. This may result in poor academic performance and an increased risk of social, behavioral, and neurological problems, such as cerebral palsy, epilepsy, visual and hearing impairments, as well as comorbidities like attention deficit hyperactivity disorder(ADHD), autism spectrum disorder(ASD), anxiety, depression, and schizophrenia. Several risk factors for SGA-related neurocognitive impairments have been identified, including gestational hypertension, abnormal gestational weight, smoking, and catch-up growth. Studies have shown that the best interventions to improve cognitive dysplasia include nutrient supplementation, continued breastfeeding, high-quality education, and appropriate early intervention (responsive parenting) are effective in improving cognitive outcomes for SGA children.

Objective To study the effect of ladder language training on vocabulary comprehension of children with Down syndrome(DS).Methods Fifteen DS children aged 10～18 years(average 13.89±2.42 years)were in-cluded as the experimental group and 15 DS children aged 10～18 years(average 13.56±1.81 years)were recruited as the control group.The intelligence level of the two groups was evaluated by China Binet-Simon intelligence test.The vocabulary comprehension ability of two groups of children was evaluated by Peabody picture vocabulary test re-vised(PPVT-R).The physiological age,intelligence level and vocabulary comprehension ability before intervention were matched between the two groups.The children in the experimental group had 16 ladder language training twice a week,45 minutes each time by group intervention for 16 times.The children in the control group did not receive this kind of intervention.Through comparison,the effect of ladder language training on DS children's vocabulary comprehension ability was analyzed.Results There was no significant difference in PPVT-R scores between the ex-perimental group(39.6±11.04)and the control group(39.93±10.61)before training(P＞0.05).After training,the PPVT-R score of DS children in experimental group(48.53±11.23)was significantly higher than that in con-trol group(40.2±10.63)(t(28)=2.086,P＜0.05)and was extremely significantly higher than that before training(39.6±11.04)(t(14)=-8.956,P＜0.001).There was no significant difference in PPVT-R scores between DS children in the control group before and after training(t(14)=-1.468,P＞0.05).The scores of children's under-standing abilities of nouns,verbs and adjectives in DS group after training were all higher than 80％,which was sig-nificantly higher than that before training(P＜0.001).Conclusion Ladder language training can significantly im-prove the vocabulary comprehension ability of DS children.

This paper discusses the mechanism of acupuncture for diabetes mellitus from the perspective of molecular biology, aiming to reveal the potential rules of restoring the balance in the body and fighting against diabetes mellitus (DM). By searching the basic research literature of acupuncture treatment for DM, it is found that the molecular biological mechanism of acupuncture treatment for DM is closely related to the regulation of insulin signaling pathway, the modulation of inflammatory response, the protection and regeneration of islet β-cells, fat metabolism and energy balance. It points out that there are few studies of acupuncture on the type 1 diabetes mellitus and the large-scale randomized controlled trials, as well as the studies on the upstream regulation mechanism, the specific cellular molecules and the interaction mechanism of various molecules. It needs to deepen the multi-level, multi-target and multi-dimensional exploration on the molecular biological mechanism of acupuncture for diabetes mellitus.
Humans ; Acupuncture Therapy ; Diabetes Mellitus/genetics* ; Animals ; Insulin/metabolism* ; Signal Transduction

OBJECTIVE: To explore the genetic basis of two fetuses with an osteogenesis imperfecta (OI) phenotype. METHODS: Two fetuses diagnosed at the Affiliated Hospital of Weifang Medical College respectively on June 11, 2021 and October 16, 2021 were selected as the study subjects. Clinical data of the fetuses were collected. Amniotic fluid samples of the fetuses and peripheral blood samples of their pedigree members were collected for the extraction of genomic DNA. Whole exome sequencing (WES) and Sanger sequencing were carried out to identify the candidate variants. Minigene splicing reporter analysis was used to validate the variant which may affect the pre-mRNA splicing. RESULTS: For fetus 1, ultrasonography at 17+6 weeks of gestation had revealed shortening of bilateral humerus and femurs by more than two weeks, in addition with multiple fractures and angular deformities of long bones. WES revealed that fetus 1 had harbored a heterozygous c.3949_3950insGGCATGT (p.N1317Rfs*114) variant in exon 49 of the COL1A1 gene (NM_000088.4). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was classified as a pathogenic variant (PVS1+PS2+PM2_Supporting) for disrupting the downstream open reading frame resulting in premature translational termination, being de novo in origin, and lacking records in the population and disease databases.For fetus 2, ultrasonography at 23 weeks of gestation also revealed shortening of bilateral humerus and femurs by one and four weeks, respectively, in addition with bending of bilateral femurs, tibias and fibulas. Fetus 2 had harbored a heterozygous c.1557+3A>G variant in intron 26 of the COL1A2 gene (NM_000089.4). Minigene experiment showed that it has induced skipping of exon 26 from the COL1A2 mRNA transcript, resulting in an in-frame deletion (c.1504_1557del) of the COL1A2 mRNA transcript. The variant was inherited from its father and had been previously reported in a family with OI type 4. It was therefore classified as a pathogenic variant (PS3+PM1+PM2_Supporting+PP3+PP5). CONCLUSION The c.3949_3950insGGCATGT (p.N1317Rfs*114) variant in the COL1A1 gene and c.1557+3A>G variant in the COL1A2 gene probably underlay the disease in the two fetuses. Above findings not only have enriched the mutational spectrum of OI, but also shed light on the correlation between its genotype and phenotype and provided a basis for genetic counseling and prenatal diagnosis for the affected pedigrees.
Pregnancy ; Female ; Humans ; Osteogenesis Imperfecta/genetics* ; Collagen Type I, alpha 1 Chain ; Collagen Type I/genetics* ; Mutation ; Fetus

Objective: To evaluate the effects of overweight and obesity intervention in the health-promoting school model and to provide reference for effective prevention and control of overweight and obesityin middle Schools. Methods: Using stratified cluster random sampling, 10 middle schools in Sanmenxia City were randomly divided into intervention group and control group. In the intervention group and the control group, one middle school and one high school were randomly selected. The students from the two classes randomly selected in the first and second grades in the four schools that were selected, the questionnaire survey and medical examination was conducted before and after the intervention to evaluate the intervention effect. Results: After intervention, the ratio of overweight and obesity of the intervention group decreased from 22.70% before intervention to 17.45%, statistical significance(χ 2=4.11, P<0.05), and the ratio of overweight and obesity of the control group increased from 22.39% before intervention to 22.91%, no significant difference(P>0.05). After the intervention, the response rates of limiting red meat, fried food and sugarsweetened beverages were all higher than those before the intervention, the differences were statistically significant (χ 2=125.73, 10.69, 208.55, 170.66, 50.01, P<0.01). Conclusion The comprehensive intervention measures of overweight and obesity in the model of health promotion school can encourage students to develop healthy behaviors and effectively prevent and control middle school students from overweight and obesity, and it is easy to form a long-term intervention mechanism.

Objective:To explore the implementation method of case teaching in pharmacology teaching according to the standards of golden course.Methods:The students from Batch 2017 clinical medical students in our university were selected as the research objects, and randomized into the control group ( n=121) and the case teaching group ( n=171). The control group used online learning and traditional lecture, and the case teaching group adopted the online teaching and case teaching methods. And the teaching effect was evaluated by questionnaire survey and final performance analysis. Results:Compared with control group, the case teaching group had better final performance ( P<0.01). The questionnaire survey showed that the case teaching improved the learning interest of students and also enhanced their application ability of the knowledge ( P<0.01 or P<0.05). Conclusion:Case teaching has achieved good teaching effect in pharmacology teaching.

Although current direct anti-hepatitis B virus (HBV) drugs have good effects in controlling viral replication and limiting the progression to liver cirrhosis, there is still a long way to go in the treatment of chronic hepatitis B (CHB). Immune tolerance and immune dysfunction may be the two most important immunopathogenic factors. With reference to the development of new strategies and new drugs for anti-HBV immunotherapy and the latest research findings around the world, this article reviews the research advances in immunotherapy for CHB in recent years.

Objective To observe and explore the effects of different tidal volume (VT) ventilation on right ventricular (RV) function in patients with critical respiratory failure.Methods Consecutive respiratory failure patients who were treated with invasive ventilator over 24 h in the Department of Critical Care Medicine at the Fourth Hospital of Hebei Medical University from June to December in 2015 were enrolled in this study.Clinical data including patients′ vital signs, ventilator parameters and RV echocardiography were collected within 6 h (D0), day1(D1), day2 (D2) and day3 (D3) after ventilation started.According to the VT, patients with acute respiratory distress syndrome (ARDS) were assigned to low VT group [S6, ≤6 ml/kg predicted body weight (PBW)] and high VT group (L6, >6 ml/kg PBW), while non-ARDS patients were also assigned to low VT group (S8, ≤8 ml/kg PBW) and high VT group (L8, >8 ml/kg PBW).Results A total of 84 patients were enrolled in this study.44.2% ARDS patients and 58.5% non-ARDS patients were in low VT groups.After ventilation, tricuspid annulus plane systolic excursion(TAPSE)decreased progressively in S6 [from 18.30(16.70,20.70) mm to 17.55(15.70,19.50) mm, P=0.001], L6 [from 19.50(17.00,21.00) mm to 16.30(15.00,18.00) mm P=0.001], S8[from 18.00(16.00,21.00) mm to 16.50(15.50,18.00) mm, P=0.001] and L8 [from 19.00(17.50,21.50) mm to 16.35(15.15,17.00) mm, P=0.001] groups.However, TAPSE decreased less in small VT groups (S6 and S8) than those of in large VT groups (S8 and L8) without significant differences.There were not statistical differences between different VT groups in terms of ventilation days, including right ventricle area/left ventricle area (RVarea/LVarea),TAPSE,peak mitral flow velocity of the early rapid filling wave (E),peak mitral flow velocity of the late rapid filling wave (A),early diastolic velocity of the tricuspid annulus (e′),pulmonary artery systolic pressure,inferior vena cava diameter (all P>0.05).Compared to L6 group, low VT (S6 group) resulted in decreased mortality at 28 days [1/19 vs 37.5%(9/24), P=0.014].There were not statistical differences between different VT groups in terms of ventilation days, length of intensive care unit stay, length of hospital stay (all P>0.05).Logistic regression analysis showed that VT could be the independent factor of TAPSE (OR=1.104,95%CI 0.100-1.003,P=0.049).Conclusions Positive pressure mechanical ventilation resulted in RV systolic dysfunction.Lower VT may have the protective effect on RV function.Trial registration Chinese Clinical Trial Registry,ChiCTR-POC-15007563.