Objective:To investigate the effects of maternal consumption of A1-type β-casein protein free (A1PF) bovine milk during lactation on breast milk composition and gastrointestinal health in term breastfeeding mother-infant dyads.Methods:This two-arm, double-blind, randomized controlled pilot study was conducted at Jinhua Wenrong Hospital and Qiubin community health center (Wucheng district, Jinhua) from June 13 to August 17, 2023. Participants were randomly assigned to the A1PF group (A1PF milk, 25 dyads of term) or control group (regular milk, 25 dyads of term). Mothers consumed 200 ml of assigned milk twice daily for 14 days. Breast milk composition, maternal gastrointestinal health, and their effects on gastrointestinal health and crying-sleep patterns of infants were analyzed at baseline, day 1, and day 14. Statistical analyses included independent t-test, paired t-test, Mann-Whitney U, Wilcoxon signed-rank, and Fisher's exact tests. Results:Calcium [A1PF group: (1.68±0.26), (1.78±0.24), and (2.17±0.21) mmol/L, F=8.62; control: (1.75±0.26), (1.79±0.31), and (2.05±0.31) mmol/L, F=4.69] and iron concentrations [A1PF group: (1.19±0.31), (1.26±0.28), and (1.79±0.27) μg/ml, F=7.85; control: (1.09±0.41), (1.16±0.31), and (1.38±0.31) μg/ml, F=3.87] increased significantly over time in both groups (all P<0.001). At day 14, A1PF group showed higher breast milk iron and zinc levels [(24.72±5.15) vs. (21.56±3.82) μmol/L] versus control ( t=4.23 and 2.31; both P<0.05). Maternal biomarkers in A1PF group exhibited reduced salivary levels of interleukin-4 [480.89 (457.20-509.50) vs. 526.34 (475.03-561.97) ng/L; Z=－2.25], interleukin-6 [19.27 (18.83-21.47) vs. 21.75 (20.15-23.29) ng/L; Z=－3.50], immunoglobulin A [15.18 (14.62-16.59) vs. 16.72 (15.02-17.64) μg/ml; Z=－2.27], immunoglobulin E [3.95 (3.81-4.33) vs. 4.43 (4.16-4.57) μg/ml; Z=－2.91], elevated salivary glutathione [(97.07±5.84) vs. (93.30±6.94) ng/L; t=2.02], and increased fecal short-chain fatty acids [568.50 (452.74-795.26) vs. 371.22 (288.32-556.07) μg/ml; Z=2.18] on day 14 (all P<0.05). Corresponding improvements occurred in breastfed infant salivary/fecal biomarkers. No significant differences in crying or sleep patterns were observed (all P>0.05). Conclusions:Compared to regular milk, A1PF milk consumption reduces maternal gastrointestinal/systemic inflammation and improves gastrointestinal symptoms among term mothers, with benefits extending to breastfed infants. However, a large multi-centered clinical trial is required to confirm this conclusion.

Objective:To investigate the effects of maternal consumption of A1-type β-casein protein free (A1PF) bovine milk during lactation on breast milk composition and gastrointestinal health in term breastfeeding mother-infant dyads.Methods:This two-arm, double-blind, randomized controlled pilot study was conducted at Jinhua Wenrong Hospital and Qiubin community health center (Wucheng district, Jinhua) from June 13 to August 17, 2023. Participants were randomly assigned to the A1PF group (A1PF milk, 25 dyads of term) or control group (regular milk, 25 dyads of term). Mothers consumed 200 ml of assigned milk twice daily for 14 days. Breast milk composition, maternal gastrointestinal health, and their effects on gastrointestinal health and crying-sleep patterns of infants were analyzed at baseline, day 1, and day 14. Statistical analyses included independent t-test, paired t-test, Mann-Whitney U, Wilcoxon signed-rank, and Fisher's exact tests. Results:Calcium [A1PF group: (1.68±0.26), (1.78±0.24), and (2.17±0.21) mmol/L, F=8.62; control: (1.75±0.26), (1.79±0.31), and (2.05±0.31) mmol/L, F=4.69] and iron concentrations [A1PF group: (1.19±0.31), (1.26±0.28), and (1.79±0.27) μg/ml, F=7.85; control: (1.09±0.41), (1.16±0.31), and (1.38±0.31) μg/ml, F=3.87] increased significantly over time in both groups (all P<0.001). At day 14, A1PF group showed higher breast milk iron and zinc levels [(24.72±5.15) vs. (21.56±3.82) μmol/L] versus control ( t=4.23 and 2.31; both P<0.05). Maternal biomarkers in A1PF group exhibited reduced salivary levels of interleukin-4 [480.89 (457.20-509.50) vs. 526.34 (475.03-561.97) ng/L; Z=－2.25], interleukin-6 [19.27 (18.83-21.47) vs. 21.75 (20.15-23.29) ng/L; Z=－3.50], immunoglobulin A [15.18 (14.62-16.59) vs. 16.72 (15.02-17.64) μg/ml; Z=－2.27], immunoglobulin E [3.95 (3.81-4.33) vs. 4.43 (4.16-4.57) μg/ml; Z=－2.91], elevated salivary glutathione [(97.07±5.84) vs. (93.30±6.94) ng/L; t=2.02], and increased fecal short-chain fatty acids [568.50 (452.74-795.26) vs. 371.22 (288.32-556.07) μg/ml; Z=2.18] on day 14 (all P<0.05). Corresponding improvements occurred in breastfed infant salivary/fecal biomarkers. No significant differences in crying or sleep patterns were observed (all P>0.05). Conclusions:Compared to regular milk, A1PF milk consumption reduces maternal gastrointestinal/systemic inflammation and improves gastrointestinal symptoms among term mothers, with benefits extending to breastfed infants. However, a large multi-centered clinical trial is required to confirm this conclusion.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

Objective To establish a dynamic model of lipopolysaccharide-induced acute lung injury in mice based on the NLRP3/Caspase-1/gasdermin D(GSDMD)pyroptosis pathway,and observe the result ing lung injury at different time points.We aimed to identify the optimal time for modelling according to the injury at different time points and the expression of pyroptosis pathway-related proteins,to lay the foundation for animal models for subsequent experiments.Methods Fifty-four 6～8 weeks old male SPF BALB/c mice were divided randomly into nine groups,including Con group and model groups at 1,3,6,12,18,24,48,and 72 h.Body weight and lung tissue were detected by general and pathological observations and semi-quantitative scoring,including lung index,lung water content,and wet and dry weight ratio.The white blood cell count and concentrations of tumor necrosis factor-α,interleukin(IL)-6,IL-1β,IL-18,and BCA protein were detected in bronchoalveolar lavage fluid(BALF).The classic pyroptosis pathway-related proteins NLRP3,pro-Caspase 1,Caspase 1,and GSDMD were detected by Western Blot.Results Body weight decreased in all experimental groups,with the most significant weight loss in the 24 and 48 h groups.Gross observation and pathological examination of lung tissue showed that the most severe lung injury occurred at 24～72 h,with significant differences between each group and the control group.The lung index,lung water content,and wet/dry weight ratio were also significantly increased at 24～72 h.White blood cells in BALF started to increase from 6 h after model initiation,48 h can reach a peak,72 h all keep increasing.IL-18 in BALF began to increase at 24 h and continued to increase at 72 h.The inflammatory factors tumor necrosis factor-α,IL-1β,IL-6 were highest at 6 h and significantly reduced at 48 h.Protein concentrations in BALF were significantly increased within 24,48,and 72 h compared with those in the control group.The pyroptosis pathway proteins NLRP3,pro-Caspase-1,Caspase-1,and GSDMD were significantly enhanced in each time series,and channel protein expression was significantly enhanced at 24～72 h compared with that in the Con group.Conclusions Comprehensive analysis of experimental indicators,inflammatory factors,and pathway proteins at different times showed that the mechanism of pyroptosis was closely related to the occurrence and progression of acute lung injury.Expression of the pyroptosis pathway was most obvious and lung injury was most serious at 24～48 h.This study provides a model reference and experimental basis for subsequent studies of the specific mechanism and intervention targets of acute lung injury.

Objective:To elucidate the change of whole genome expression profile for the effect of melatonin on radiation-induced intestinal injury in mice.Methods:C57BL/6J male mice were administrated with melatonin at 10 mg/kg body weight by intraperitoneal injection once a day for five consecutive days before abdominal irradiation with 14 Gy of γ-rays. Small intestines were harvested 3 d after radiation. GO annotation and KEGG pathway of the differential genes involved in small intestine were explored by DNA microarray analysis.Results:Compared with the control group, 584 differential genes were up-regulated and 538 differential genes were down-regulated for administration group pre-irradiation. The overlapping differential genes were selected from the irradiated mice and the administrated mice pre-irradiation. There were 324 up-regulated genes and 246 down-regulated genes unique to the administrated mice pre-irradiation. GO annotation analysis of the differential genes indicated that the top 15 significantly enriched biological processes for the administrated mice pre-irradiation mainly included autophagosome assembly (GO: 0000045), autophagosome organization (GO: 1905037) and regulation of acute inflammatory response (GO: 0002673). The genes ATG12, ATG16L2 and AMBRA1 were involved in autophagosome assembly and autophagosome organization. The genes C3, CPN1, CD55, CFP, CNR1, C1QA, C2 and CREB3L3 were involved in the regulation of acute inflammation response. KEGG pathway analysis of the differential genes involved indicated that the top 15 significantly enriched pathways for the administrated mice pre-irradiation mainly included O-glycan biosynthesis (hsa00512), glycosphingolipid biosynthesis (hsa00603), ECM-receptor interaction (hsa04512) and biosynthesis of unsaturated fatty acids (hsa01040). qRT-PCR verification showed that the expressions of ATG12 and ATG16L2 genes involved in autophagy for the administrated mice pre-irradiation increased significantly compared with the irradiated mice ( t=2.40, 4.35, P<0.05). Conclusions:The differential genes related with the biological process of autophagy, acute inflammatory response and the pathway of unsaturated fatty acid biosynthesis might be involved in the effect of melatonin on radiation-induced intestinal injury.

Objective:With the rapid increase in the number of real world studies, especially the use of health data in medical institutions, ethical issues such as the use of patient health data and the protection of patient′s privacy rights and the right to know have been gradually exposed. To strike a good balance between promoting data sharing and maintaining subjects′ personal privacy, the mode of informed consent appears to be crucial. This paper provided guidance for the selection of informed consent models for real world research health data utilization.Methods:The authors extensively studied the relevant laws and regulations of health data utilization worldwide, conducted extensive searches in Chinese and English databases, sorted out and analyzed various alternative informed consent models, and summarized their characteristics and applications.Results:At present, five alternative informed consent models were used to conduct real world research based on health data utilization. Researchers can choose informed consent models according to the research purpose, research design, research risk, operability of informed consent, and vulnerable groups.Conclusions:Different alternative informed consent models have varied characteristics. Researchers need to choose informed consent models based on the above factors to ensure the maximum protection of patients' privacy rights while using health data.

This article is a summary of the Second China Breast Milk Science Conference, which was held in Beijing from August 5 to 7, 2022, with the theme of "Data sharing, method sharing and science sharing". The purpose of the conference is to summarize the latest progress in breast milk research, identify the unresolved issues, and jointly discuss the direction of future breast milk research. Firstly, we summarize the contents and purpose of breast milk scientific research and prospect of breast milk science. The second part focuses on the research status of breast milk composition and its health effects, and puts forward the future research direction. The third section focuses on the health effects of breastfeeding and scientific support and key aspects of breastfeeding promotion actions. The fourth part elaborates the specific methods of current scientific research of breast milk and emphasize the importance of method standardization and the idea of future methodological research. The fifth part consists of the strategy of feeding infants with medical conditions and ways to better promote the growth and development of these infants. The last part introduces the innovation, deficiencies, and future research directions of infant formula production technology in China. This conference demonstrate the importance of multidisciplinary communication, discussions and collaborations in clinical medicine, nutrition, perinatal health, food science, and policy-making in the scientific research of breast milk, and provides guidance for future multidisciplinary research on the physiology of lactation, the composition of breast milk, breastfeeding, and infants and young children nutrition.

Cardiometabolic disease (CMD), characterized with metabolic disorder triggered cardiovascular events, is a leading cause of death and disability. Metabolic disorders trigger chronic low-grade inflammation, and actually, a new concept of metaflammation has been proposed to define the state of metabolism connected with immunological adaptations. Amongst the continuously increased list of systemic metabolites in regulation of immune system, bile acids (BAs) represent a distinct class of metabolites implicated in the whole process of CMD development because of its multifaceted roles in shaping systemic immunometabolism. BAs can directly modulate the immune system by either boosting or inhibiting inflammatory responses via diverse mechanisms. Moreover, BAs are key determinants in maintaining the dynamic communication between the host and microbiota. Importantly, BAs via targeting Farnesoid X receptor (FXR) and diverse other nuclear receptors play key roles in regulating metabolic homeostasis of lipids, glucose, and amino acids. Moreover, BAs axis per se is susceptible to inflammatory and metabolic intervention, and thereby BAs axis may constitute a reciprocal regulatory loop in metaflammation. We thus propose that BAs axis represents a core coordinator in integrating systemic immunometabolism implicated in the process of CMD. We provide an updated summary and an intensive discussion about how BAs shape both the innate and adaptive immune system, and how BAs axis function as a core coordinator in integrating metabolic disorder to chronic inflammation in conditions of CMD.

Objective To analyze the survival and toxicity after concurrent chemoradiotherapy in patients of different ages with stage Ⅳ non-small cell lung cancer (NSCLC).Methods Clinical data of 282 NSCLC patients in two prospective studies were retrospectively analyzed,who completed the protocol (at least 2 cycles of chemotherapy and thoracic radiation doses of ≥36 Gy).Among them,44 patients were assigned into in the young group (≤ 45 years old),161 patients in the middle-age group (46-64 years old) and 77 patients in the elderly group (≥ 65 years old).The clinical characteristics of patients among different groups were analyzed by x2 test.The overall survival (OS) was calculated by Kaplan-Meier method.Stratified analysis was performed by Log-rank test.Multi-factor prognosis analysis was conducted by Cox's proportional hazards regression model.Results The incidence of NSCLC in the male patients in the elderly group was higher than that in the middle-age and young groups.The 1-,2-,3-and 5-year OS did not significantly differ among different groups (P=0.810).The OS did not significantly differ among patients of the same gender,pathological type,T stage,N stage,metastasis status,same chemotherapy cycle,primary tumor dose and comprehensive treatment and short-term response (all P＞0.05).The incidence of adverse events did not considerably differ among different groups.Multivariate analysis demonstrated that age was not an independent factor for survival (P＞ O.05).Conclusion Patients of different ages with stage Ⅳ NSCLC obtain similar survival benefits and adverse events after concurrent chemoradiotherapy.

Objective To investigate the impact of the changes of posttreatment karnofsky performance status (KPSpost) on the overall survival (OS) for patients with stage Ⅳ non-small cell lung cancer (NSCLC) underwent concurrent chemoradiation.Methods A total of 279 patients (male 198 and female 81) with histological confirmed stage Ⅳ NSCLC were enrolled in this study with a median age of 58 years old (range 22 to 80 years old).There were 166 cases of squamous carcinoma,87 cases of adenocarcinoma,and 22 cases of unclassified carcinoma,respectively.All enrolled patients received more than 2 cycles of chemotherapy and more than 36 Gy of concurrent radiotherapy.Kaplan-Meier method and Log-rank test were applied to evaluate OS.Multivariate analyses were carried out by the Cox proportionalhazard model.Chi-square test and logistic regression analysis were used to explore the related factors of KPSpost.Results There were 198 patients with improved KPSpost and 81 patients with decreased KPSpost,respectively.Univariate and multivariate analyses indicated that the improvement of KPSpost was associated with longer OS.Logistic regression analysis showed that the improvement of KPSpost was positively related with treatment of more than 4-6 cycles chemotherapy concurrent with over 63 Gy radiation to primary tumor.The improvement of KPSpost also correlated positively with disease control rate (DCR),but negatively with PLT toxicity and radiation esophagitis.Conclusions KPSpost was an independent prognostic factor of OS for patients with stage Ⅳ NSCLC underwent concurrent chemoradiation.Chemotherapy of 4-6 cycles and concurrent over 63 Gy radiotherapy dose to primary tumor,as well as DCR were positive factors for KPSpost improvement.However,stage 3-4 PLT toxicities and radiation esophagitis decreased the KPSpost.