The present study aimed to investigate the status and relationships between family support for infant and toddler care and parenting stress, and to explore differences related to the number of children in the families. We conducted a survey among 13,390 Chinese parents who were randomly sampled from six provinces of China. Descriptive analysis, multivariate analysis of variance, and regression analysis indicated that (1) current family support for infant and toddler care in China is insufficient; (2) most Chinese parents reported moderate parenting stress, with the highest scores given for parental distress, followed by difficult child, and parent–child dysfunctional interaction; (3) the larger the number of children in the family, the less the family support for infant and toddler care, the greater the parenting stress; (4) there was a difference between the effects of family support for infant and toddler care on relieving parenting stress among families with different numbers of children. These findings indicate that different types of family support for infant and toddler care should be provided for families with different numbers of children, to ease parenting stress and promote the implementation of the government’s current fertility policy. Supporting the well-being of children is a priority of the national welfare policy . The estIn the context of limited family support for infant and toddler care, parents inevitably encounter practical problems such as work–family conflict in the process of parenting ,12,13,14Previous studies have investigated family support for childcare and parenting stress separately ,20. HoweThe efficient strategic provision of family support for infant and toddler care is critical for promoting family well-being . As incrWith the strengthening of policy guidance on infant and toddler care, research attention regarding this field is increasing. Some studies have revealed a mismatch between the demand and supply of infant and toddler care support ,27. HoweExistence, relatedness, and growth (ERG) theory assumes that human beings have three core needs that each individual strives to fulfill, from low- to high-level requirements. On the basis of ERG theory, family’s needs could be divided into three categories, including obtaining the means of material existence, maintaining interpersonal relatedness to significant others, and seeking opportunities for a unique personal development and growth ,30,31. TIn the current study, family support for infant and toddler care were considered to be an important part of life-cycle service management . ReferriRaising children involves both joyful moments and challenges over many years . When thReliable and valid instruments are necessary for measuring parenting stress effectively. Abidin (1990)  developeFrom a family systems perspective , the addAccording to the buffering model , social Previous studies have suggested that families with multiple children are likely to experience more stress and greater challenges than those with one child and require more care support ,21. FamiWhat types of support for infant and toddler care do Chinese families perceive exist? Are there differences among families with different numbers of children?What are the characteristics of parenting stress experienced by Chinese families? Are there differences among families with different numbers of children?Which types of family support for infant and toddler care could substantially alleviate parenting stress among families with different numbers of children?With the rapid development of China’s economic and social policies and labor market, dramatic changes have taken place in the family. These changes have led to the weakening of traditional family-based care systems for children under the age of 3, increasing the demand for alternative social childcare . In the A stratified cluster sampling approach was employed to recruit families with children under 3 years old. This study was part of a project commissioned by the National Health Commission of the People’s Republic of China, and the survey was conducted in representative provinces across the country. First, we randomly selected six provinces: Beijing, Shanghai, Shanxi, Henan, Guizhou, and Yunnan. These provinces represent the Eastern, Central, and Western regions of China, and reflect China’s different economic levels and educational development levels. Second, we randomly sampled two cities from each participating province, resulting in 12 participating cities. Third, for the above-mentioned target cities, with the assistance of the local health department, e-questionnaires were distributed via community WeChat groups, and parents with children under the age of 3 were invited to participate in the survey. Finally, a total of 13,390 valid questionnaires were returned for this national survey. The sample covered the Eastern (34.4%), Central (39.4%), and Western (26.2%) regions, providing a geographically representative Chinese population. Among the respondents, 33.1% were located in rural areas and 66.9% of families were located in urban. The sample included 5503 (41.1%) one-child families, 6454 (48.2%) two-children families, and 1443 (10.7%) three or more-children families.The family support for infant and toddler care questionnaire was designed as a nationally representative survey to investigate infant and toddler care support from families’ perspective in China. This questionnaire includes two sections: demographic information, and family support for infant and toddler care. The first section of the questionnaire mainly investigated the demographic information of families with children under 3 years old. In addition to the geographic region , living area , and number of children  presented above, we also investigated the following information and they were coded as categorical data. Monthly family income was measured on a three-point scale: 1 = under CNY 5000, 2 = CNY 5001–CNY 10,000, 3 = CNY 10,001 or above. Education attainment was measured on a 3-point scale: 1 = senior high school education or below, 2 = up to 3 years of college education, and 3 = 4 years or more of university study. According to Lu (2002), occupational level in China can be categorized into nine groups. Parental occupation ratings were assigned a code number from 1 to 9, with larger numbers indicating greater occupational prestige. In addition, family work status was also examined . Family income, maternal and paternal education, and paternal and maternal occupations were standardized (Z-score), and SES was then identified as an observed construct using five standard scores. This section of the survey also asked about the child’s primary caregiver .In the second section, investigation of family support for infant and toddler care was mainly based on the ERG theory and the Guiding Opinions . ERG theParenting stress was assessed using the Parenting Stress Index-Short Form (PSI-SF) . The PSIEthical procedures were followed throughout the research process. First, we used e-questionnaire for investigation, which proved to have good reliability . In ordeThe survey data were collected and analyzed using IBM SPSS 25.0. For the first and second research question, we provided descriptive statistics to reveal the types of infant and toddler care support and parenting stress perceived by Chinese families, and used multivariate analysis of variance (MANOVA) to analyze the difference by families with different numbers of children. To answer question three, correlation analyses between demographic variables  and dependent variables were first conducted, so that the relevant variables could be controlled in further analyses. We then explored which types of infant and toddler care support were perceived as playing a significant role in relieving parenting stress in families with different numbers of children using regression analyses.M] = 0.45, standard deviation [SD] = 0.30), followed by existence support , and the lowest was the growth support .The perceived level of currently available family support for infant and toddler care was low. Regarding the status of family support for infant and toddler care, the score for relatedness support was highest  = 32.71, p < 0.001, η2 = 0.01 . Additionally, differences in the number of children were only found in relatedness support, F = 80.29, p < 0.001, η2 = 0.01. However, there was no significant effect for existence support, F = 14.43, p < 0.001, η2 = 0.002, and growth support, F = 4.97, p < 0.01, η2 = 0.001. Finally, the post-hoc analysis indicated that the perceived support differed by the number of children  on the perceived infant and toddler care support. The results revealed a significant major effect of the number of children, Wilks’ λ = 0.985, dren See . The supM = 3.50, SD = 0.78) had the highest score, followed by difficult child , and parent–child dysfunctional interaction . Thus, the results indicated that among Chinese families, caregivers most commonly experienced stress related to the challenges of parenting, whereas relatively few caregivers experienced stress related to parent–child dysfunctional interaction.Most Chinese parents reported experiencing moderate stress, with the means of the overall score being slightly higher than 3.0. Parental distress  = 40.29, p < 0.001, η2 = 0.01, and the power to detect the effect was 1. Next, differences related to the number of children were found for two constructs: difficult child, F = 112.98, p < 0.001, η2 = 0.02 and parent–child dysfunctional interaction, F = 96.90, p < 0.001, η2 = 0.01. However, there was no significant effect on parental distress, F = 31.59, p < 0.001, η2 = 0.005. Finally, a post-hoc analysis indicated that parenting stress was differentiated by the number of children (See ps < 0.001), and the pressure in two-child families was significantly greater than that in one-child families (ps < 0.001). Overall, the results revealed that a greater number of children in the family was associated with higher parenting stress.We conducted MANOVAs to explore the possible effects of the number of children on parenting stress. The results revealed a significant effect of the number of children . Specifically, we examined main effects of overall satisfaction and found a significant effect of the number of children, Wilks’ λ = 0.962, dren See . The preps < 0.01). Meanwhile, eight of the family support for infant and toddler care were significantly associated with parenting stress and were also included in subsequent regression models. In addition, we verified the common method bias using the Harman single-factor test.First, Pearson’s correlation analysis was conducted to explore the correlation between control variables, family support for infant and toddler care, and parenting stress in China. As shown in Next, linear regression with the enter method was then conducted to examine the impact of family support for infant and toddler care on parenting stress. The independent variables were nested at two levels: (1) demographic variables: geographic region , living area , family SES , family work status , and primary caregiver ; (2) family support for infant and toddler care: existence support ; relatedness support ; growth support . Accordingly, demographic variables were entered in Step 1, and eight family supports for infant and toddler care as independent variables were entered in Step 2. To further examine the differences among families with different numbers of children, three separate regression models were constructed. The regression model results are shown in β = −0.08, p < 0.001), growth inspection , and disease prevention . Regarding growth support, play venues  and childcare services  also showed a significant effect.For the one-child families, basic existence support had the most significant effect on relieving parenting stress, including all support for this dimension: newborn visits , growth inspection , and disease prevention . In relatedness support, flexible working hours significantly reduced parenting stress . Regarding growth support, play venues  and childcare services  showed a significant effect.For the families with two children, existence support also had the most significant effect on relieving parenting stress, newborn visits . Additionally, the effect of social childcare services was also significant .For families with three or more children, the effect of existence support and relatedness support on parenting stress was no longer significant, while the effect for growth support was still significant. These families reported needing play venues for children (In summary, the regression analyses revealed that family supports for infant and toddler care were critical predictors of parenting stress. For families with different numbers of children, growth support has a significant effect on relieving parenting stress. At the same time, there were differences in the relief effects of various types of support on parenting stress. Families with one child tended to report needing more basic existence support, as well as growth support. In addition to existence support and growth support, relatedness support such as flexible working hours was reported to be important for relieving stress in families with two children. Finally, families with three or more children tended to report that they no longer needed basic existence support and relatedness support, but had more of a need for play venues for their children; at the same time, alternative childcare services were reported to be useful for easing parenting pressure.The current study provided new empirical evidence regarding the current situation and relationships between family support for infant and toddler care and parenting stress in China under the three-child policy. Falling fertility is an increasingly global problem. Despite differences within and between regions, fertility rates are declining rapidly or stabilizing at relatively low levels in most parts of the world. In terms of promoting the implementation of government fertility policies, it is not sufficient to simply encourage families to have children. It is critical to improve support to help families relieve the pressure of child rearing. The current findings extend our understanding of how to improve the support measures of fertility from the perspective of family needs. Additionally, the current findings suggest an approach for improving family support for infant and toddler care in low-fertility societies such as China and many other countries. In the following section, we discuss the current findings and their implications for infant and toddler care and family well-being practice.Researchers in the fields of childcare and early education have long been aware that efforts should be made to encourage child-oriented initiatives with a focus on supporting parents ,67. HoweAt present, family care is still the main source of care for children under 3 years old in China . ChineseIn the current study, we found that Chinese families experienced a moderate level of parenting stress, which is consistent with the survey results in recent years ,61, and The birth of a new child, and the first weeks, months, and years of a child’s life, are times in which the tension between work obligations and child rearing is particularly acute. According to a survey of 10,155 parents from 21 cities conducted by the China Women’s Federation, over 50.0% of two-child families experienced parenting challenges and stress . For exaFamily support for infant and toddler care is considered to be an important tool to help families balance work and life, which can relieve the stress of parenting ,41. The This study aimed to understand the current situation regarding family support for infant and toddler care and parenting stress, and which types of family support for infant and toddler care can relieve parenting stress in the context of China’s three-child policy. The results revealed several key findings. First, the currently available family support for infant and toddler care in China is insufficient. Second, most Chinese parents reported experiencing moderate parenting stress. Among the types of stress, parental distress was most common, followed by difficult child, and parent–child dysfunctional interaction. In addition, a larger number of children in the family was reported to be associated with greater parenting stress but less family support for infant and toddler care. Finally, family support for infant and toddler care could relieve parenting stress in families with different numbers of children.The current study involved several limitations. First, we examined family support for infant and toddler care as well as parenting stress on the basis of self-reported data from parents. Although we can intuitively understand the experiences of parents, we cannot objectively and comprehensively understand the current situation regarding care support and parental stress. Multidimensional evaluation, instead of sole reliance upon questionnaire data, should be undertaken to avoid response biases such as the social expectation effect from different populations. Future studies should investigate multiple stakeholders and enrich research methods. Second, this study shows that family support for infant and toddler care has a certain effect on parenting stress, but this effect is limited. In addition to family support for infant and toddler care, parenting stress can also be affected by many factors such as parenting style, and socioeconomic status ,80. The Nevertheless, our findings have many implications for policymakers in China, and internationally. To address the current situation, in which family support for infant and toddler care has been unable to adapt to changing family needs, it is important to adhere to the concept of sustainable development directed by family demand, by promoting supply-side structural reform, accelerating the construction of care support systems for infants and toddlers in China, effectively alleviating the pressure of family rearing and care difficulties, promoting the well-being of families and the healthy growth of children, and helping the implementation of government fertility policies. First, the health and safety of infants and toddlers should be protected. Local governments should provide community maternal and child health services. Through the establishment of comprehensive information systems for community maternal and child health, effective integration and sharing of health information database resources should be undertaken to form a comprehensive and interconnected service information network. Second, parental leave and flexible working policies that can balance family and work should be fully implemented, and husbands and wives should be encouraged to share responsibility for family affairs and childcare. Additionally, family-friendly workplace arrangements should be provided, including flexible working hours and locations, as well as support for women who have had a career break to return to work. Finally, ample play venues and the provision of childcare services should be strengthened to resolve challenges of childcare and parenting. The developing brain exhibits sensitive periods, and while they may vary slightly from child to child, the most sensitive periods are around birth and in the first 3 years. Family policies should be developed that enable children and their parents to thrive, so that all individuals can contribute in a rapidly changing environment.


In the recent era, nursing needs employees with moral intelligence, cultural competence, and self-compassion skills more than ever. This study aimed to determine the predictors of moral intelligence and its relationship with self-compassion and cultural competence in nursing students.This cross-sectional and multi-center descriptive study was conducted in 2022. With convenience sampling, 250 nursing students from three Iranian universities participated in this study. Data gathering included the Moral Intelligence Questionnaire, Self-Compassion Scale (short form), and Cultural Competency Questionnaire. The data were analyzed using descriptive statistics, the correlation between variables, and hierarchical regression.r = 0.11, p = 0.07). Moral intelligence with marital status , academic year  and self-compassion  had a significant relationship in such a way that these variables explained 15% of moral intelligence and self-compassion had the highest impact (p < 0.001).The results showed that nursing students had good moral intelligence (72.63 ± 11.38), moderate self-compassion (37.19 ± 5.02), and poor cultural competence (50.06 ± 13.15). No statistically significant relationship was observed between self-compassion and cultural competence (Considering the moderate level of self-compassion and the poor level of cultural competence reported in the undergraduate nursing students, and also that self-compassion was known to be a predictive factor for moral intelligence, planners and educators must pay more attention to promoting self-compassion and cultural competency in the curriculum and conduct studies to find ways to improve them. Moral intelligence is managing the problem-solving and conflict-resolution process with dedication and conscious participation in interpersonal and intrapersonal communication is referred to as a term that has recently been introduced in the nursing profession –3. MoralSelf-compassion is the ability to communicate with the self’s emotions and well-being . There iCultural competence is the perception of patients’ values, beliefs, and health practices that manifests itself in the ability of caregivers to communicate effectively with individuals from different cultures . The carIn addition to clinical qualifications, nursing students in clinical education settings should have the necessary mental and psychological traits, moral principles, and intelligence . ParticuSome studies demonstrate the connection between cultural competence and morals , 18, 19 This is a cross-sectional, multi-center descriptive study from three universities; Semnan University of Medical Sciences, Semnan, Iran; Tehran University of Medical Sciences, Tehran, Iran; and Lorestan University of Medical Sciences, Khorramabad, Iran, which was conducted from December 2021 to March 2022.The participants in this study were undergraduate nursing students in their second year and above. They were chosen by a convenience sampling method. The inclusion criteria for this study contained completing the first year of a nursing bachelor’s degree because, in Iran, undergraduate nursing students enter clinical environments from the second year, willingness to participate in the study, and incomplete completion of the questionnaires.r = 0.25 [Based on a similar study by Gottlieb, the Pearson correlation coefficient between cultural competence and self-compassion was Data collection tools included four questionnaires of demographic information, moral intelligence, self-compassion, and cultural competence. Permission was obtained from the instrument developers for the moral intelligence, self-compassion, and cultural competence instruments. The demographic information questionnaire included six questions: age, sex, marital status, university of study, academic year, and grade point average (Grading is based on a 0 to 20 score).It was developed by Lincoln Keel with 40 items on a five-point Likert-type scale . This questionnaire can measure the four dimensions of moral intelligence, including integrity (items 1–10), responsibility (items 11–20), compassion items 21–30), and forgiveness (items 31–40). The final score is divided by two, and the obtained number is placed between the two points, 20 and 100. Finally, score categorization would be designed as 90–100 (excellent), 80–89 (very good), 70–79 (good), and 69 or lower (weak) –30, and .This tool was developed by Neff . Raes crThis questionnaire consists of 20 items. It was developed and validated by Khanbabaei for the Iranian population. This questionnaire has three dimensions of learning and education : awareness and knowledge  and skill . The items are rated on a five-point scale . The score categorization would be designed as 93–100 (very strong), 81-92 (strong), 80 64 (moderate), 44-63 (weak), and 20-43 (very weak). Cronbach’s alpha coefficient of this questionnaire is 0.91, and the intragroup correlation coefficient is 0.93 [Before starting the sampling, necessary permits for data collection were obtained from the authorities. In the sampling stage, the objectives of the research were fully explained to the participants so that they could withdraw from the study at any stage if they wished. Also, they were informed that the results of the research would be provided to them if they were interested. The data was collected face to face through a paper questionnaire and with previous coordination by referring to educational and clinical environments by the researcher.Demographic variables were described using statistical indicators of absolute frequency, mean, standard deviation, skewness, and kurtosis indices. Pearson and Spearman correlation tests were used for the inferential section, and hierarchical multiple linear regression tests were used to test research hypotheses. Spearman’s test was used for ordinal variables. The maximum alpha error level to test the hypotheses was set at 0.05. Data analysis was done with SPSS 27.Two hundred fifty nursing students from three universities participated in this study. Skewness and Kurtosis tests showed that all main variables had a normal distribution.The findings showed that the majority of the participants were female (6.59%); single 6.91%); in the age group of 21 to 23 years (6.65%); with a grade point average of 15-17 (53.2%); were studying in the second year (38%); and a majority of participants were from Semnan University of Medical Sciences (2.35%),  and academic year . So married students in a lower academic year had higher moral intelligence than others. The results of the Pearson correlation test showed that self-compassion had a significant relationship with total scores of moral intelligence  , responsibility , compassion , and forgiveness .The results of Pearson and Spearman correlation tests show there was a significant relationship between moral intelligence and marital status (1) Table . Also, t2) showed that the predictor variables could explain 15% of the changes in moral intelligence (p > 0.001). The findings showed that the variables of marital status , academic year  and self-compassion  can predict moral intelligence. Furthermore, the highest effect was related to self-compassion, with a coefficient of 0.34 , responsibility (embracing liability for behaviors and outcomes of some behaviors and defeats), compassion (sympathetic pity and concern for the suffering or misfortune of others), and forgiveness (perception of one’s defects and wrongs) . These dWe revealed that the cultural competence of our participants was at a weak level. The consequences of the same studies on nursing students demonstrate that cultural competence in South Korea was medium to high , and in Although, we did not observe a significant relationship between cultural competence and moral intelligence in undergraduate nursing students. However, the perception and intuition of nurses about the vulnerability of patients from various cultures illustrate their moral sensitivities in conducting ethical decisions . Due to Moreover, according to the study’s results, a significant relationship was not seen between self-compassion and cultural competence in undergraduate nursing students. Gottlieb’s study in the U.S. demonstrated a significant relationship between self-compassion and cultural competence in social work students, and self-compassion was considered a strong predictor of cultural competence in these students . AcquiriThis study showed that married students had higher moral intelligence than single students. Also, Gholami et al.’s study indicated that married nurses had higher moral intelligence. Since different genetic, psychological, and social factors affect moral intelligence , it seemThis study showed that students in higher academic years have lower moral intelligence. Among the possible reasons, we can mention the choice of wrong models during education, the student’s attention to improving practical skills, and neglecting morals. Teaching the basic nursing courses and ethics in the undergraduate nursing curriculum in the first years of study influences the fading of moral intelligence during the study course. We could find no accurate studies that addressed this issue.Finally, the results of this research can be used to develop knowledge related to the concept of moral intelligence, which has recently entered the nursing profession and identify ways to improve it. The results of this study can help policy makers, nursing managers, and educational designers to design and implement more effective educational programs in order to have nursing students and nurses with high moral intelligence.One of the strengths of the present study is examining and measuring the correlation of several concepts with moral intelligence. The second strength of this study is the multi-center study design that was carried out on students in medical sciences universities in three provinces that can develop the generalizability of the outcomes. There were also limitations in this study. First, there were many questionnaires, and participants completed them slowly, so it was challenging to convince them. We overcame this problem more patiently and continued communication with the research participants. Since the data gathering tools were completed self-reporting, the respondents’ bias and social desirability can be increased. On the other hand, convenience sampling limited the results’ generalizability. Moreover, understanding the causality of the relationships between variables requires further studies. Therefore, some observational studies are needed to clarify the relationships between variables.The results of this study demonstrated that the moral intelligence of the Iranian undergraduate nursing students was at a reasonable level, and there was a relationship between moral intelligence and marital status, students’ academic year, and self-compassion. Also, married students in the lower academic year had higher moral intelligence than others. According to the fact that the level of self-compassion was reported as moderate and the level of cultural competency was reported to be weak, and also self-compassion was found to be a predictive factor for moral intelligence, planners and educators must pay more attention to the promotion of self-compassion and cultural competence in curricula and studies are conducted to find ways to improve them.


Background: Aloe vera were frequently reported to reduce the risk of radiation-induced dermatitis (RID), but the quantitative results from all the relevant studies were not presently available. This study sought to conduct a cumulative analysis to better clarify the preventive effects of aloe vera in RID.Methods: MEDLINE (PubMed), Cochrane, EMBASE, PsychINFO, Web of Science, China National Knowledge Infrastructure (CNKI), and Wan Fang Database were utilized for identifying the eligible randomized controlled trials (RCTs) without language restrictions, up to March 2022. The pooled incidence of RID was conducted by the Relative risk (RR) with its 95% confidence interval (CI) through the STATA software under a random-effects model. This systematic review and cumulative analysis were registered on PROSPERO (ID: CRD42022335188).Results: Fourteen RCTs met our predefined inclusion criteria, enrolling 1,572 participants (mean age: 46.5–56 years). The cumulative results revealed that patients pretreated with aloe vera were associated with a significantly lower risk of RID compared to those without aloe vera usage . In the subgroup analysis, the pooled incidence of Grade 2–4, Grade 2, and Grade 3 RID was also dramatically lower in the group of aloe vera as compared to the placebo group . However, in regard to Grade 4 RID, the combined RR indicated that the incidence of RID was comparable between aloe vera and the control group . The sensitivity analyses showed that there was no substantial change in the new pooled RR after eliminating anyone of the included study.Conclusion: The current cumulative analysis revealed that patients pretreated with aloe vera were less likely to suffer from RID than the controls without using aloe vera. Based on this finding, the prophylactic application of aloe vera might significantly reduce the incidence of RID, especially in Grade 2 and Grade 3 RID. Further large-sample multicenter RCTs are still warranted to confirm these findings and for better clinical application. Cutaneous disease is a global public health concern and brings immense health and economic burden on society because of its increasing prevalence. Since the worldwide population are rapidly ageing, the prevalence and the profile of skin diseases are growing, leading it to becoming a public health problem entailing an enormous socio-economic burden . Of the Approximately 50% of diagnosed cancer patients will receive radiotherapy alone or in combination with surgery or chemotherapy . RadiatiAloe vera (L.) Burm.f. (Aloe vera), a traditional Chinese medicine cataloged in the Pharmacopoeia of the People’s Republic of China, had been widely used traditionally for the treatment of constipation, wound healing, anorexia, and dyspepsia . Aloe veAlthough the association between aloe vera and radiation dermatitis had been extensively studied, the effects of aloe vera in the prevention or treatment of radiation dermatitis were conflicting. Therefore the systematic review and cumulative analysis aim to provide a better understanding of the effectiveness and safety of aloe vera in the prevention or treatment of radiation dermatitis and to provide objective meaningful information to guide clinicians in clinical practice.http://www.crd.york.ac.uk/PROSPERO).This systematic review and cumulative analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines . The detMEDLINE (PubMed), EMBASE (OVID), Cochrane Library databases, PsychINFO, Web of Science, China National Knowledge Infrastructure (CNKI), and Chinese Wan Fang Database were systematically searched for the relevant studies up to March 2022. The searching strategy was restricted to human subjects, while there were no language restrictions for the published articles. The searching keywords in PubMed database for English language was: {[“Aloe” (Mesh)] OR (Aloe vera)} AND {[“Dermatitis” (Mesh)] OR (Dermatitides)}.The occurrence and severity of RID were diagnosed were graded using the Radiation Therapy Oncology Group (RTOG) standard, at the end of radiation therapy. According to the RTOG, the severity of RID would be 0 to 4 categories: grade 0, grade 1, grade 2, grade 3, and grade 4. High grade indicated greater severity of RID. Other assessments were also considered to be eligible, e.g., RID could be judged by a health care provider, as reported in the included studies.for this cumulative analysis was: Does aloe vera decrease the risk of RID? The compositions for the PICOS evidence were: cancer patients under radiation therapy (P); the usage of aloe vera (I); compared to those without aloe vera (C); the diagnosis of RID (O); any study designs (S). Furthermore, any trials presented with the relative risk (RR) and its 95% confidence intervals (CI) were also considered to be eligible.The inclusion criteria for this study were listed as followed. 1) The study design should be conducted according to the patient, intervention, comparison, outcome, and study design (PICOS); The question guiding in vitro and in vivo studies were excluded. Studies that failed to provide the data from the control participants were also excluded. Moreover, those publications belonging to review, comment, letter, and case reports could be also eliminated.In this study, we only included studies that reported human subjects, thus the The relevant information was independently extracted by two authors through a standardized data collection form. These data included the first authors’ names, country or region of the study, study design, the publication year, gender, types of cancer radiotherapy, dose of radiation (Gy), study period, the demographic and mean age of the participants with both groups, type of aloe vera, and assessment of RID.The risk of bias among the included studies was judged by Cochrane’s risk of the bias assessment tool. Based on the guideline of the Cochrane collaboration, the quality of the eligible studies was evaluated by the study design, methodology, and analysis. According to the different items, the included study could be assessed by a three-point scale: yes (low risk of bias), no (high risk of bias), and unclear (without specific statement).p value < 0.05 were presumed as statistically significant. The I2 statistic analysis was performed to identify the heterogeneity of a combined analysis. I2 > 50% was considered to be substantial heterogeneity, while p-value of the Q test < 0.10 was assessed to be statistically significant. Since the presence of the different study designs as well as the study sample, a random effect model was applied when combining the RR. To detect the origin of the substantial heterogeneity, a sensitivity analysis was performed. Both Begg’s rank correlation test and Egger’s regression asymmetry test were used to assess the publication bias. In this cumulative analysis, the statistical analyses were performed with both the STATA  and the RevMan review management software (version 5.4).The cumulative RR with the corresponding 95% CI was applied to evaluate the strength of the association between aloe vera treatment and the risk of RID. Results derived from the combined RR with a two-tail During the initial searching, 201 studies were detected. Among them, 91 publications were derived from PubMed and 37 publications were from the CNKI, while the remainder of 73 studies were detected from the EMBASE, Cochrane Library databases, PsychINFO, Web of Science, and Wan Fang Database. Based on a review of the titles and abstracts, 167 publications were eliminated due to duplicate and ineligible issues, leaving 34 potential studies for further full-text evaluation. Of which, 20 studies were eliminated for reasons, e.g., eight studies did not comply with the research question, five studies for failing to meet the inclusion criteria, four studies for insufficient outcome data, and three studies being to as a review or comment article. Finally, a total of fourteen studies  were conThe descriptive characteristics of the fourteen eligible studies were summarized in Among the fourteen included studies, only p < 0.001; heterogeneity: I2 = 79.8%, p < 0.001). Of note, Hong et al. and As shown in p = 0.002; heterogeneity: I2 = 69.1%, p = 0.002). When separated by each Grade of RID, the cumulative RR derived from eight included studies consistently suggested that pretreatment with aloe vera might significantly reduce the incidence of Grade 2 RID compared to the controls . The above results revealed that no single study could dominate the combined RR and the heterogeneity.To evaluate the effect of the single study on the combined quantitative synthesis of RR and the heterogeneity, a sensitivity analysis was properly conducted. As shown in p > |z| = 0.064)   . Howevero −0.96) .p < 0.001). In line with this finding, pretreatment with aloe vera was also associated with a significantly lower risk of Grade 2–4 RID when compared to the controls . In regard to each grade of RID, aloe vera could reduce the risk of Grade 2 by 42%  and Grade 3 by 73% . Subsequent sensitivity analyses revealed that no single study could dominate the overall combined RR. Therefore, the present evidence was robust.Acute dermatitis is a common adverse effect after radiation therapy, affecting over 90% of the patients. The severity of RID varied from erythema to ulcer and necrosis. There are currently numerous methods to prevent, reduce, and treat radiotherapy skin toxicities based on the experiences of the clinicians. Mounting evidence suggests that the traditional medicinal herbs and their extractives have an excellent effect on anti-RID, such as Jaungo, Plantago lanceolate folium, Heijiangdan Ointment, and aloe vera . Aloe veAs reported, aloe vera is found to contain over 70 potentially active constituents, e.g., vitamins, enzymes, salicylic acids, and amino acids . In 1995It was known that ionizing radiation is the direct cause of radiation dermatitis. DNA damage is considered to be the direct consequence of high dose ionizing radiation. Ionizing radiation had been shown to induce DNA damage and cell death . MeanwhiVascular damage is associated with the pathogenesis of radiation dermatitis . AdditioAs far as we know, this is the first study to quantify the protective effects of aloe vera on RID through a cumulative analysis. Multiple strengths should be acknowledged in the present study. This is a meta-analysis of all the available studies with a larger sample with an evidence-based etiological theory. As a result, the present evidence is creditable for clinical practice. Nevertheless, several inherent limitations could not be ignored when interpreting this data. First, substantial heterogeneities existed in a combined analysis. In general, different study designs, sample sizes, ages of the participants, geographical areas, and confounding factors could all be partly responsible for this remarkable heterogeneity. Second, we only included those studies that were published in English and Chinese, which may induce a selection bias. Third, different ages and various types of cancers were found in these included studies, which may downgrade the evidence of this study. Thus, caution is warranted when interpreting this study. Besides, additional well-designed RCTs with large samples are still warranted to further illuminate the effects of radioprotection developed by aloe vera.Based on the current evidence, pre-treated with aloe vera was reinforced to significantly reduce the incidence of RID as compared with the conventional treatment. Aloe vera could be served as a standardized product in the prevention or treatment of RID in patients with malignancies, especially for breast cancer and nasopharyngeal carcinoma. On account of the small quantity of relevant RCTs, the conclusions should be interpreted carefully. In the near future, further multicenter RCTs with a large sample size would be required to confirm this finding.


The spleen and lymph nodes are important functional organs for human immune system. The identification of cell types for spleen and lymph nodes is helpful for understanding the mechanism of immune system. However, the cell types of spleen and lymph are highly diverse in the human body. Therefore, in this study, we employed a series of machine learning algorithms to computationally analyze the cell types of spleen and lymph based on single-cell CITE-seq sequencing data. A total of 28,211 cell data  involving 24 cell types were collected for this study. For the training dataset, it was analyzed by Boruta and minimum redundancy maximum relevance (mRMR) one by one, resulting in an mRMR feature list. This list was fed into the incremental feature selection (IFS) method, incorporating four classification algorithms . Some essential features were discovered and the deep forest with its optimal features achieved the best performance. A group of related proteins  and genes (Nkg7 and Thy1) contributing to the classification of spleen and lymph nodes cell types were analyzed. Furthermore, the classification rules yielded by decision tree were also provided and analyzed. Above findings may provide helpful information for deepening our understanding on the diversity of cell types. The spleen and lymph nodes are both important secondary lymphoid organs in the human body for immune response and other immunological functions. The human body has hundreds of lymph nodes, which are strategically distributed throughout the body for lymphocytes to effectively encounter antigens and be activated . When thvia the lymph conduit and further provide conditions for the survival and activation of various immune cells  B cells, B1 B cell, and follicular B cells are very important. MZ B cells reside between the MZ and red pulp, and it is an innate-like B cell subset specific to the spleen. It can quickly produce IgM and class-switched IgG and IgA antibodies against common antigens in the first-line defense . MZ B ceAdvances in single-cell sequencing, such as the CITE-seq method (measurement with cellular indexing of transcriptomes and epitopes by sequencing) , have prIn the present study, based on the CITE-seq sequencing data of immune cells from murine spleen and lymph nodes, we computationally analyzed such data to extract gene expression signatures and biomarkers, which can characterize different spleen and lymph node cell types. Briefly, the Boruta  and miniOur research is divided into the following processes: (1) data collection, (2) classification into training and test datasets, (3) pre-processing of data, (4) feature ranking, (5) development of models, and (6) feature interpretation, as shown in https://github.com/YosefLab/totalVI_reproducibility/blob/v0.3/data/spleen_lymph_111.h5ad and https://github.com/YosefLab/totalVI_reproducibility/blob/v0.3/data/spleen_lymph_206.h5ad. To refine these two datasets, we only selected the 110 proteins and 13,553 genes that overlapped and the cells from the 24 overlapped cell types. After filtering, the first dataset included 14,435 cells, which was picked up as the training dataset, and the second dataset, including 13,776 cells, was termed as the test dataset. The sample sizes of each cell type in the training and test datasets are listed in We downloaded the single-cell CITE-seq protein and gene expression data of spleen and lymph from The download data were all CITE-sequencing data. CITE-seq method is an effective tool for single-cell level multi-omics integrative analyses and were used to identify transcriptomics profiling together with phenotypic or proteomic signatures. The general workflow of CITE-seq can be divided into three steps as follows:1)Antibodies with specific DNA barcodes can specifically bind to the target proteins/antigens;2)By using single-cell droplet library preparation methods, such as the preparation methods of 10X genomics, drop-seq, and ddseq, each cell together with its unique DNA barcodes was isolated in one droplet; and3)All the mRNAs of this single cell are indexed with the original DNA barcodes. Finally, by using next-generation sequencing and proper bioinformatics methods, we obtained the single-cell mRNA profiling information together with its respective phenotypes, such as biomarker patterns.Lots of features  were used to represent cells in the training and test datasets. Clearly, it was impossible that all of them were related to distinguish cell types. Generally, the related features occupy a small proportion. Thus, it was necessary to extract them with some advanced computational methods. Here, we selected Boruta feature selection method . Its briBoruta feature selection method is a RF -based wrhttps://github.com/scikit-learn-contrib/boruta_py was applied, and the default parameters were set.In the present study, the Boruta program provided by The features selected by Boruta should be further evaluated as it was not clear which features were more important. Thus, we further employed the widely used feature selection method, mRMR .The mRMR is a high-performance feature selection method. The original purpose was to select a compact feature subset that have high relevance to target labels and low redundancies between features in this set. However, such purpose is hard to be achieved as such problem is NP-hard. As an alternative way, it sorts features in a list, named mRMR feature list. Features with high ranks in this list are more important than others. This list is generated by repeatedly selecting features. In each loop, a feature with maximum difference between its relevance to target labels and redundancies to already-selected features is selected and appended to the current list. The relevance and redundancy are all measured by mutual information (MI) between features or target labels.http://home.penglab.com/proj/mRMR/.In the present study, the mRMR program with the default parameters was obtained from Although mRMR generated the mRMR feature list, it was still not clear which features can constitute the optimal features for distinguishing cell types. In view of this, some other computational methods were adopted.IFS is a feature selection method , which cTo execute the IFS method, at least one classification algorithm is necessary. To fully evaluate each feature subset, four powerful classification algorithms were attempted, including DF , RF Bre, KNN Co, and DT DF is a deep neural network that builds deep models based on non-differentiable modules, such as DTs. Briefly, DF builds multi-layer models through tree integration by using gradient boosting DTs as a building block for each layer, emphasizing its representational learning capability and optimization of the training process. The DF algorithm used in the present study was the Cascaded DF , which cThe RF is a non-parametric decision classification ensemble algorithm containing a number of DTs. Each DT is constructed by randomly selecting samples and features. RF aggregates the predictions of all DTs as its decision. Considering the differences between DTs, RF can avoid the overfitting problem. Although RF loses the interpretability and may slightly increase the bias, it improves the performance and reduces the error. To date, it is always an important candidate to construct classifiers in dealing with different medical problems .k nearest neighbors are extracted. Based on the labels of these neighbors, the predicted label of the test sample can be determined. Generally, the label occurring most on the k nearest neighbors is picked up as the predicted label of the test sample.The KNN is one of the most classic classification algorithms. This algorithm does not contain a training procedure. For a given test sample, its distances to all training samples are calculated and DT is also a classic classification algorithm. Different from above algorithms, which is very difficult to uncover their classification principles, DT provides an opportunity for human to understand its classification procedures as such procedures are completely open. Besides the tree-like representation of DT, it can also be represented by a set of rules. Each rule indicates a path from the root to one leaf node. Several features may be included in each rule, which constitute a special pattern for the result of the rule (label for one class). In recent years, it becomes more and more popular to analyze various complicated medical datasets .https://github.com/LAMDA-NJU/Deep-Forest. As for RF, KNN, and DT, their programs implemented through the Scikit-learn module were used. All programs were executed using default parameters.To implement above four classification algorithms, some public online sources were used in this study. In detail, the DF program was downloaded from https://github.com/scikit-learn-contrib/imbalanced-learn and it was performed with the default parameters.According to The feature interpretation includes single-genes/proteins and combined gene/protein rules. The interpretation of single genes/proteins focuses on the essential genes/proteins that are assigned high ranks in the mRMR feature list, while that of the combined gene/protein rule focuses on the rules yielded by the optimal DT classifier.The Matthew correlation coefficient (MCC)  metric iX denotes a binary matrix including the predicted label of each sample, and Y denotes another binary matrix representing the true label of each sample. The correlation coefficient of X and Y is defined as cov , and X and Y, respectively. C denotes the total number of cell types, while n denotes the number of cells. The range of MCC is between −1 and 1. Higher values of MCC indicate better performance of the classifier.where In addition, we also provided the overall accuracy and individual accuracy on each cell type to fully display the performance of all classifiers.In the present study, 28,211 cells were obtained from the two sample sets. After filtration, the two datasets, including 14,435 and 13,776 cells, respectively, were deeply analyzed. The entire procedures are illustrated in As lots of features were involved to represent cells, we first adopted Boruta to select important features from the training dataset. 1,180 features were kept, where 67 were about proteins and rest 1,113 were about genes. These remaining features were further analyzed by the mRMR method. An mRMR feature list was generated, which is provided in According to the procedures shown in To test the generalization ability of above four optimal classifiers, the test dataset was fed into each optimal classifier. The obtained ACC and MCC values are listed in According to the principle for generating the mRMR feature list, top features in such list may be essential for distinguishing cell types. The discussion part in section “Analysis of the quantitative features for distinguishing different cell types” shown that the surface proteins  and genes (Nkg7 and Thy1) have a decisive effect on different cell types. However, considering that the interaction between features is unknown, relying on one single protein or gene alone to reveal the different expression patterns of spleen and lymph node cells is not sufficient. Therefore, we further employed DT to learn classification rules. As the optimal DT classifier used the top 624 features in the mRMR feature list, a tree was learn by applying DT on all samples represented by these features. From this tree, a total of 2,675 rules were generated, which are given in As mentioned above, we utilized several machine learning methods to characterize the relationship among cell phenotypes, functions, and transcriptomes by analyzing CITE-seq data of immune cells from murine spleen and lymph nodes. The features in the investigated datasets contain the abundance of 110 surface proteins and the expression level of 13,553 genes. After using several methods, we finally constructed a DF classifier using 216 features, which can yield a high MCC of 0.868. Some top features in the mRMR feature list were deemed to be essential to distinguish spleen and lymph node cells. In addition, we further adopted DT to generate a group of decision rules, which can not only distinguish cell types but also indicate different patterns on various cell types.Based on machine learning algorithms, we identified a set of significant features that contribute to the determination of immune cell types in the spleen and lymph nodes. We reviewed several publications to prove how these features are decisive for different cell types, including surface proteins of CD4, TCRb, CD103, CD43, and CD23, and the genes of Nkg7 and Thy, which are listed in The surface protein CD4 (ADT_CD4_A0001) is a coreceptor of T cell receptors on T lymphocytes, and it can recognize antigens displayed by MHC class II molecules on antigen presenting cells. CD4 is a commonly used marker for CD4+ T cells. CD4 + T cells can differentiate into various effector cell subtypes, including T types 1, 2, and 17, follicular helper T cells, and regulatory T cells. These subtypes are all involved in regulating the immune response to different types of pathogens . SimilarThe surface protein TCRb (ADT_TCRbchain_A0120) is a subunit of the T cell receptor molecules. It can be used as a marker of T cells and is important for TCR-mediated T cell recognition of foreign antigens displayed by MHC. At the DNA level, the TCRB is synthesized through VDJ recombination events and later connected to the C segment at the RNA level. These events play an important role in the development of T cells and can provide a wide range of antigen recognition for immune cells .Protein CD103 (ADT_CD103_A0201) is also known as integrin subunit alpha E. It is highly expressed in intestinal intraepithelial lymphocytes and could be used as a biomarker for CD4+ T cells. CD103+ CD8+ T cells induced by human alloantigens have the functional characteristics of regulatory T cells, thus confirming the importance of CD103 to CD4+ T cells, especially regulatory T cells . The negThe surface protein CD43 (ADT_CD43_A0110) is a highly sialylated transmembrane glycoprotein, and it participates in cell adhesion, proliferation and the antigen-specific activation of T cells. It is expressed in various immune cells and can be used as a marker for NK cells and B cells . High CDGene Nkg7 (ENSMUSG00000004612) encodes a protein called natural killer cell granule protein 7, which is expressed in activated T cells and natural killer cells but not in B cells, monocytes, and myeloid cells . A recenGene Thy1 (ENSMUSG00000032011) encodes a cell surface glycoprotein that belongs to the immunoglobulin superfamily. It was first identified in mouse T lymphocytes and was later shown to play a role in cell adhesion and communication of multiple cell types . MoreoveThe protein CD23 (ADT_CD23_A0108) is a B cell-specific antigen that plays an essential role in B cell growth and differentiation and the regulation of IgE production. The stimulation of CD40 antigen induces the expression of CD23 and participates in the activation and maturation of B cells, and CD23 could be used as a marker of mature B cells .The features generated by the machine learning algorithms are closely related to the cell function or fate of immune cells. The differential expression of multiple genes in different cell types or tissues provides a basis for our classifier.Our results show a large number of decision rules . In someIn our decision rules for indicating spleen mature B cells, we noticed a criterion that requires the high expression of surface protein CD24. CD24 is commonly expressed on mature granulocytes and B cells, and it is very crucial for the differentiation process of cells . CD24 isThe surface protein CD103, which is also called ITGAE, showed a high expression for indicating lymph node CD8 T cells based on our analysis. This protein is preferentially expressed in intraepithelial lymphocytes and plays a role in adhesion, migration, and lymphocyte homing . CD103 iThe highly expressed CD357, also known as TNFRSF18 or GITR, can indicate the lymph node regulatory T cells based on our computational analysis. CD357 is a member of the TNF-receptor superfamily. This receptor protein plays a key role in immune regulation such as T-cell activation . CD357 iLy6-high monocytes, which are also called inflammatory monocytes, express the high level of CCR2 and decreased CX3CR1 and play important roles in inflammation. Our decision rules showed that surface protein CD49d and gene CEBPB required a relatively high expression to indicate ly6-high monocytes. CD49d, which is also called ITGA4, belongs to the intergrin alpha chain family and may play a role in cell motility and migration. The regulation of ITGA4 is associated with inflammatory diseases . GeneticResults further show that a high expression of surface protein CD43 is required to indicate the spleen NK cells. CD43 is a highly sialylated glycoprotein that functions in antigen-specific activation of various immune cells. Despite the wide distribution of CD43 in monocytes, lymphocytes, and thymocytes, it is specifically expressed on human NK cells . The difIn summary, our decision rules proposed that combined-cell surface protein or gene expression can be used to distinguish immune cell subtypes in different tissues. It validated the markers of each immune cell subtype and helps in discovering some new expression patterns of immune cells in the spleen and lymph node.The present study analyzed the single-cell CITE-seq protein and gene expression data of spleen and lymph, which involved 24 cell types. Through a computational procedure, including several machine learning algorithms, some essential features, powerful classifiers and classification rules were accessed. The analysis on the essential features, corresponding to surface proteins and genes, and rules indicated that they were related to the identification of spleen and lymph node cell types, suggesting they can be latent biomarkers for cell type identification. Furthermore, the powerful classifiers can be tools to classify spleen and lymph node cells.https://github.com/YosefLab/totalVI_reproducibility/blob/v0.3/data.Publicly available datasets were analyzed in this study. This data can be found here: TH and Y-DC designed the study. HL, SD, and SZ performed the experiments. DW, XZ, WG, and ZL analyzed the results. HL, DW, XZ, and SD wrote the manuscript. All authors contributed to the research and reviewed the manuscript.


To explore the effects of human milk fortifier (HMF) on improving the preoperative nutritional status of infants with non-restricted ventricular septal defect (VSD).n = 29) and a control group (n = 29). HMFs were added proportionally to the infants' feeds in the intervention group based on breastfeeding status, and the infants in the control group received exclusive breastfeeding as needed. The nutritional status of the two groups was compared 1 month after the intervention.A prospective randomized controlled study was conducted in a provincial hospital in China. Participants were randomly divided into an intervention group (p < 0.05). The STRONGkids score of the HMF group was significantly lower than that of the non-HMF group (p < 0.05). There was no significant difference in pneumonia, liver insufficiency, feeding intolerance, or jaundice between the two groups.Compared with the control group, the weight, head circumference, height, albumin level, and prealbumin level of the human milk fortifier group were significantly higher 1 month after the intervention (The addition of HMFs based on the breastfeeding status of infants with non-restricted VSD can improve the preoperative nutritional status and does not increase the incidence of gastrointestinal complications.http://www.chictr.org.cn/index.aspx, identifier: ChiCTR2000041135. Ventricular septal defect (VSD) is one of the most common congenital heart diseases. Infants with non-restricted VSD usually have symptoms such as shortness of breath, feeding difficulties, severely affected growth and development, moderate to severe pulmonary hypertension, and even cardiac insufficiency. Due to the large size of the defect and a large number of left to right shunts, surgical correction should be performed in infancy for these patients –3. TheseHuman milk is the ideal food for infants, and breastfeeding is known as the most beneficial way of feeding premature infants , 9. HoweThe present study was approved by our hospital's ethics committee and adhered to the tenets of the Declaration of Helsinki. Additionally, all the parents of the patients signed consent forms before participating in the study.This study was a prospective randomized controlled study conducted by a provincial hospital in China. The inclusion criteria were as follows: (1) infants with non-restricted VSD; (2) infants with no congenital malformation associated with other essential organs; and (3) infants with families who were willing to participate in the study and signed informed consent forms. The exclusion criteria were as follows: (1) patients with severe liver and kidney dysfunction; (2) patients with other severe heart structural abnormalities; (3) patients complicated with digestive insufficiency; (4) patients receiving breast milk via nasal tube feedings; (5) patients who underwent emergency surgery when the condition worsened; and (6) infants who were not exclusively breastfed.From January 2020 to June 2020, a total of 58 infants who were diagnosed with non-restrictive VSD in our hospital after birth and who were followed up in the outpatient clinic 1 month later were enrolled in this study. All the patients were diagnosed in the neonatal period. Based on the patients' clinical symptoms, ages, and weights, the clinician suggested that the patients should first be discharged for observation and then followed up in the outpatient department 1 month later to determine the timing of surgery.Calculation of the sample size was based on the difference in the infants' body weights in the two groups in the preliminary experiment. Assuming that the difference between the two independent populations is 10%, with an α = 0.05 and a β = 0.2, the calculated result for each group was 26 participants. Assuming a 10% dropout rate, the total sample size required in this study was 58 patients (29 patients per group). The patients were randomly divided into an intervention group (HMF group) or a control group (non-HMF group) according to computer-generated random numbers. When the patients agreed to participate in this study, the researchers randomized the grouping in a double-blind manner and collected the relevant data. During the same period, 75 patients met the eligibility criteria, and 17 were ultimately excluded, including 5 patients who underwent emergency surgery, 10 patients who were switched to nasal tube feeding or formula feeding during follow-up, and 2 parents of infants who declined to participate .The STRONGkids scoring scale was developed by Hulst et al. for nutritional status assessment. It included high-risk diseases, subjective clinical assessment, nutritional intake, and a decrease or no increase in body weight . The scoAll infants included in the study were fed breast milk. The patients in the intervention group received HMFs proportionally based on breastfeeding status. After the grouping was completed, HMF was added to fortify the patients' nutrition. All patients in the intervention group received breastmilk via bottles. Parents initially prepared more milk with the fortifier and then fed the infant according to their needs, so we could calculate the amount of feed and fortifier. Nestlé, Germany produced the HMF that was used in this study. The HMF was started at a 1/4 dose of fortifier (25 ml human milk: 0.25 g HMF). After excellent tolerance was confirmed for 3 days, the HMF was gradually added to a 1/2 dose of fortifier (25 ml human milk: 0.5 g HMF). After good tolerance was confirmed for another 3 days, the HMF was added to a full dose of fortifier (25 human milk: 1 g HMF). After that, a breast milk fortifier was added at this fixed-rate, and infants were fed on demand (25 ml human milk: 1 g HMF). In the control group, all the patients also received breastmilk via bottles, and the feeding method was the same as that in the intervention group, but with the addition of maltodextrin powder as a placebo.The nutritional status of the patients was evaluated via outpatient review 1 month after the intervention. If complications occur during the intervention, such as at least one feeding intolerance, necrotizing enterocolitis, pneumonia, liver insufficiency, jaundice, gastrointestinal bleeding, or even death, we stop the intervention and initiate immediate intervention. Nutrition-related indicators, including body weight, head circumference, height, hemoglobin level, albumin level, prealbumin level, and the STRONGkids score, were collected.The general data, including the patients' age, gender, weight, the diameter of VSD, left ventricle volume, pulmonary artery pressure, and breast milk intake were recorded. The nutritional status and complications between the two groups after the intervention in the two groups of patients were collected by an independent third investigator. Liver insufficiency was defined as ALT > 2 times the normal value of the same age, or total bilirubin >40 mg/L. Feeding intolerance was defined as gastric residual volume >50% of the administered feed volume over the previous 3 h on more than one occasion, the occurrence of any gastric distention and vomiting and/or diarrhea defined as >4 stools per day of a watery consistency. Diagnosis of NEC is carried out by Bell's staging criteria, described in the 1970's, that utilize clinical and radiological characteristics .2 test or Fisher's test was used for categorical variables. A p-value of < 0.05 was defined as statistically significant.SPSS 25.0 software was used for statistical analysis. Continuous data are presented as the mean ± standard deviation and range. The two groups' clinical parameters were compared with the independent samples t-test when these parameters were normally distributed. The χThe calorie of 100 ml breast milk was 68 kcal, and the calorie of 100 ml breast milk after adding HMF was 85 kcal. Moreover, the contents of protein, fat, and trace elements were also higher in the intervention group . There wp < 0.05). There was no significant difference in hemoglobin levels between the two groups (p > 0.05). The STRONGkids score of the HMF group was significantly lower than that of the non-HMF group (p < 0.05)  .The comparison of preoperative complications showed no significant difference in the incidence of pneumonia, liver insufficiency, feeding intolerance, and jaundice between the two groups. There were no complications, such as necrotizing enterocolitis, gastrointestinal bleeding, or death, in the two groups . All patNon-restricted VSD is a relatively severe type of VSD that often requires surgical treatment in infancy –3. With Human milk is the best food for infants, contains many nutrients needed for the growth and development of infants, and has the advantages of enhancing infants' resistance and immunity and protecting the digestive tract mucosa , 9. AlthHMF contain a variety of proteins, carbohydrates, minerals, and vitamins, which can increase breast milk energy by 5% to 10% and can strengthen the effects of breastfeeding, optimize protein intake and promote development and physical growth. At present, HMFs have been widely used for preterm infants and even very low-weight preterm infants for nutritional support to promote their growth and development and improve their nutritional status, which has achieved good clinical results. Marino LV et al. conducted a retrospective study and showed that HMF could improve the growth and development of low-weight preterm infants who were exclusively breastfed after discharge . Tewari The subjects of this study were infants with non-restricted VSD in outpatient follow-up, and these patients had mild cardiac insufficiency and were given cardiotonic and diuretic drugs. All patients in both groups received breastmilk via bottles, and HMF was applied before surgery. The results of the study showed that the weight, head circumference, albumin levels, and prealbumin levels of the infants in the HMF group were significantly higher than those in the non-HMF group. These results indicated that the HMF could improve nutritional status and reduce malnutrition risk before surgery. Studies have shown that STRONGkids can effectively assess the nutritional risk of children with congenital heart disease during the perioperative period, and provide a basis for nutritional support , 23. TheThere were some limitations in this study. This study was a single-center study with small sample size. In this study, non-breastfed or mixed-fed infants were not included, and infants with severe symptoms requiring nasal tube feeding, hospitalization, or emergency surgery, were not also included. These might have caused case selection bias. The limited evaluation indices for the results might affect the accuracy of the results. In addition, the research subjects of this study were limited to unrestricted VSD, and the study period was short. Whether such research results could be generalized remains to be further verified.Adding HMFs for breastfeeding infants with non-restricted VSD is beneficial to their overall growth and weight growth, improving preoperative nutritional status, and does not increase the incidence of gastrointestinal complications. It is worthy of clinical application.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Fujian Maternity and Child Health Hospital. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.Y-FL, QC, and Y-RZ designed the study, performed the statistical analysis, participated in the operation, and drafted the manuscript. W-HL, S-HL, and Q-LZ collected the clinical data. All authors read and approved the final manuscript.This study support by promotion of appropriate technology projects to Rural and Urban Communities, Fujian Province, China (2020TG007).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Findings of ectopic hepatocellular carcinoma (EHCC) have been rarely documented. Complicated clinical features and unpredictable medical prognosis make diagnosis and treatment difficult.in toto. Meanwhile, a 1 cm × 1 cm mass in the body of the stomach was found that was removed simultaneously. Histopathology showed that the pancreatic tumor was ectopic hepatocellular carcinoma (EHCC), and that the gastric nodule was gastrointestinal stromal tumor (GIST). The patient had an uneventful postoperative recovery. He has been living without recurrence for over 7 years since surgery. Owing to our knowledge, this is the second-longest disease-free survival time for EHCC in the literature.We reported a 59-year-old male patient who came to the hospital with epigastric discomfort and regurgitation of gastric acid. An enhanced CT scan revealed a 1.8 cm × 1.4 cm mass in the tail of pancreas without any positive finding in the liver. Postoperative MRI scan was performed but did not reveal any evidence of hepatic tumor. The tumor was resected Here, we present a rare case of EHCC in the pancreas, and review the current literature on EHCC. Operation was an effective treatment for patients with curable EHCC. EHCC with metastasis still needs more practice to improve the poor prognosis. The finding of ectopic liver accidentally happens in abdominal surgery and autopsy. It develops in various locations such as the gallbladder, intra-abdominal ligaments, omentum, peritoneum, retroperitoneum, and thorax –3. NeverThe diagnosis of EHCC before a pathological result is complicated because of various clinical features. Blood tests and imaging cannot give a significant clue. At the same time, treatment for EHCC does not have a gold standard, and it still needs more practice. In this study, we report a rare case of a combination of ECHH and GIST, which were both successfully treated with tumor resection and 7 years follow-up without recurrence. After the case presentation section, a detailed literature review of EHCC was performed.A 59-year-old man visited our hospital with epigastric discomfort and regurgitation of gastric acid in April 2014. There were no remarkable findings in the past medical history. He denied alcohol and drug abuse history. The abdomen was soft and without palpable mass. Tests for hepatitis B virus and hepatitis C virus were negative. Other laboratory examinations were regular, including low levels of CEA, CA19-9, and AFP . No significant indication was observed in hepatic function and routine blood examination. The contrast-enhanced computed tomography (CT) demonstrated a slight oval mass with irregular enhancement, which measured ~1.8 cm × 1.4 cm in the tail of pancreas. Moreover, impression of pancreatic duct dilation or stenosis was not detected by magnetic resonance imaging (MRI). By careful evaluation with the radiologist, there was no noticeable abnormality in the liver shown on CT. The postoperative contrast-enhanced magnetic resonance imaging (MRI) also confirmed the speculation on the hepatic condition .Traditional laparotomy was performed, which revealed nothing but a tumor in the pancreatic space that was mentioned in previous CT. The surface of the tumor was yellow and well-demarcated, and had a focal hemorrhagic appearance . The proConsent for publication was signed by our patient and approved by the Ethics Committee of the Fifth People's Hospital of Shanghai.We searched MEDLINE and EMBASE in February 2022 and the search strategy was “ectopic” and “hepatocellular” and “carcinoma” in title, abstract, and key-words. Included cases must provide confirmed pathological images, follow-up examination, and treatment methods. In the end, 27 cases were available for the criteria (including our case) , 5–27. AAs it is known, ectopic liver tissue and development of cancer from ectopic liver tissue is a rare condition . The ectin vitro . Two of three cases were diagnosed with EHCC before treatment or operation , 16. TheTwenty-six patients underwent operations in our review, and radical resection was performed on 24 patients. Majority of these patients who underwent a radical operation recovered well. At the same time, six of the 24 patients had recurrence after radical resection , 18, 22.The recommendation for diagnosis of EHCC is biopsy before operation. The AFP of blood test and hepatocyte-paraffin-1 of IHC are valuable for a definitive diagnosis of EHCC. Radical operation is necessary for a curable case. TACE, chemotherapy, and targeted therapy (like Sorafenib) are optional for patients with metastasis or multiple nodules. More cases of EHCC still need to be recorded to evaluate the prognosis and option for different treatments, especially long-time surveillance.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by Ethics Committee of The Fifth People's Hospital of Shanghai. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.BG and JL collected the data. QL analyzed the data and wrote the manuscript. BG, XZ, YP, and JL revised the important intellectual content and helped in the final approval of the article. All authors read and approved the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The COVID-19 pandemic led to visiting restrictions (VRs) of patients in hospitals. Social contacts between patients' relatives play an important role in convalescence. Isolation may cause new psychological comorbidity. The present study investigated the psychological distress of VR in in-patients and their relatives.From April 1, 2020 to May 20, 2020, 313 in-patients (≥14 years) of the University Medical Center Rostock were interviewed by questionnaires and 51 relatives by phone. Subjective psychological distress was assessed by a distress thermometer [0 −100 (extreme)]. The study also investigated stressors due to VR, psychological distress in dependence on demographic or disease-related data, currently used communication channels and desired alternatives and support.p = 0.002). Loss of direct physical contact and facial expressions/gestures resulted in the most distress. Psychological distress due to VR was independent of demographics and indicates small positive correlations with the severity of physical restriction and the general psychological distress of in-patients. The most frequent ways of communication were via phone and social media. Frequently requested alternatives for patients were other interlocutors and free phone/tablet use, for relatives visiting rooms with partitions.Relatives were more psychologically distressed by VR than in-patients (59 ± 34 vs. 38 ± 30, VRs are a stressor for patients and their relatives. The establishment of visiting rooms with partitions and the free use of phones/tablets could reduce the additional distress. As social beings, humans depend on interactions with others in group bonds and relationships. Especially during states of exception as hospitalization social contacts and clear targeted communication are of great relevance; however, depending on the situation often limited.Information exchange regarding disease and therapy between physician, patient, and relatives has been shown to influence patient satisfaction, treatment outcome, the healing process, and compliance –4. ContaThe prospective study was designed as a two-arm cross-sectional study. A survey of in-patients and their relatives (relative was defined as the most important contact person) was conducted by questionnaire in person (patients) or by telephone interview (relatives).From April 1st until May 20th, 2020, a self-designed questionnaire survey of in-patients (age ≥14 years) was conducted at 17 somatic clinics of the University Medical Center Rostock (UMR) with various areas of care. Questionnaires were only handed out to patients once during their stay with a length of stay ≥ 2 days. Further inclusion criteria were: ability to consent, German-speaking, and physical and cognitive ability to complete a questionnaire. For underage patients (14–17 years), these criteria applied with regard to the legal guardians. The patient questionnaire was administered during the informed consent interview to minimize the number of contacts. Questionnaires were distributed and collected by medical staff, nursing staff, and study center staff.Patients were asked to provide a relative with contact details. If a relative was named, the study center staff contacted that person by telephone. After consent was given, the interview was conducted according to a standardized interview template. The interviews had an approximate duration of 10 min.Participation in the survey was voluntary, and all patient/relative data were analyzed in a pseudonymous manner. The study was reviewed and approved by the ethics committee of the University of Rostock (A2020-68).From March 13th, 2020, strict visiting restrictions to the in-patient areas of the Rostock University Medical Center applied. In individual cases, it was possible to deviate from this procedure. This resulted in inconsistent procedures for different areas. In wards with primarily cure-oriented intentions, patients with palliative diseases were under certain circumstances allowed to receive visitors. On the palliative ward, a maximum of two visitors per day were allowed to visit dying patients, only. Minor children were allowed to be accompanied by a healthy caregiver. The procedure in each individual case was determined by the facility manager of the respective department. The senior physicians in charge of the wards ensured implementation in consultation with the nursing teams. From May 20th, 2020, the strict visitation restrictions were abolished. Patients were then allowed to receive visits from caregivers again under strict conditions. This marked the end of this survey.Assessed were age, gender, living situation, and the patient-relative relationship .The following questions were asked of the patient: reason (diagnosis) for hospitalization, duration of illness to date, whether first hospitalization/in-patient stay, number of days spent as an in-patient, and expected length of stay.Patients and relatives were asked to indicate on a distress thermometer  how much they are currently physically restricted and under psychological pressure.All participants were asked by means of 5-level Likert scales how important communication is in everyday life and direct communication with relatives, friends, etc. to them.Patients and relatives recorded: preferred frequency of visits, missed communication elements , understanding of the visitation restrictions, the general and personal perception of the VR on 5-point Likert scales, and the severity of the communication restriction. The strength of subjective psychological distress as a result of the VR was recorded using a distress thermometer . To be able to assess which proportion of the patients/relatives were distressed and to what extent, the following grouping was performed: Value “0” on the visual analog scale (VAS) = “not stressed,” VAS > 0 ≤ 30 = “slightly stressed,” VAS > 30 ≤ 70 = “moderately stressed,” VAS > 70 ≤ 90 = “highly stressed,” and VAS > 90 = “very highly stressed.”Patients and relatives were asked to provide information about the technologies used and ways of communication under the given conditions. In addition to given answer options, the respondents had the opportunity to add further technologies. Furthermore, wishes and possibilities for improvement in communication were surveyed. In addition to the predefined answer options, there was also the possibility of free-text options.p ≤ 0.05. Cramer's V (CV), effect size (ES), and correlation coefficient r, respectively, were used to interpret the strength of the relationships depending on the scale level. SPSS 22.0  was used for the statistical analysis of the data.In addition to descriptive analysis, interval-scaled data were tested for normal distribution using the Shapiro–Wilk test. Depending on the scale level, correlations and mean differences were tested using the Pearson chi-square test, Spearman correlation, and Mann–Whitney U test, respectively. The level of significance was set at A total of 313 patients participated in the survey. These provided eligible 85 relatives, 51 of whom agreed to the interviews.n = 2). The mean age of the total cohort was 60 ± 16 years. Two hundred and seventeen (69%) of the patients lived with partner(s) and/or child(ren) at the time of hospitalization (Table 2).The questionnaires were completed by 120 (38%) women and 191 (61%) men .Interviews were conducted with 51 relatives (40 (78%) women and 11 (22%) men) with an average age of 60 ± 13 years. Seventy-eight percent of the relatives were married to the patients . The relInformation on disease-related data can be found in Of all patients, physical impairment with a mean of 44 ± 29 was reported, and the current psychological distress with 38 ± 29.p < 0.001, ES = 0.466 and p = 0.043, ES = 0.200, respectively; The 51 family members reported a mean of 16 ± 23 for physical limitation and 54 ± 30 for current psychological distress. There were significant mean differences between patients and relatives for both factors . Direct communication with relatives, friends, etc. was considered (very) important by 76% of patients and 92% of relatives . Most frequently, both, patients and relatives, missed direct physical contact and nonverbal communication by means of facial expressions and gestures.Desired visit frequencies and missed communication elements are shown in Comprehension of the VRs was 96% for each of the patients and relatives, respectively.p = 0.002). The sex-stratified analysis shows a higher psychological distress of the relatives in both genders compared to the patients .p < 0.001) or general psychological distress (p < 0.001). These associations did not become apparent to relatives. The variance resolution between the parameters “general psychological distress” and “psychological distress due to VR” was 21% (patients) and 8% (relatives).As shown in Of the 51 relatives, eight (16 %) had special visitation rights during the study period. The most frequently used means of communication were telephony and social media, which were used by 45 (88 %) and 32 (63 %) patient/relative pairs, respectively. Videotelephony was used to communicate by 11 (22%) patients/relatives pairs .Of all in-patients, 19 (37%) wished for other interlocutors  as alternative visitors. Twelve (24%) wanted free bed phones and eight (16%) free use of tablet/PC. Relatives primarily used free text when indicating desired alternatives. Analysis of responses revealed that 16 (32%) desired patient visitations and suggested visitation rooms with partitions  as an option.The study revealed that VR in hospitals to control the COVID-19 pandemic is an additional stressor for patients and their relatives. In the investigated cohort of in-patients and their relatives regardless of gender, relatives were more psychologically stressed by VR than patients. Direct physical contact and facial expressions/gestures were missed most by patients and relatives. Visitor rooms with partitions are a potential alternative to reduce psychological distress due to VR, especially for relatives. In the following, the causes and possible consequences of psychological distress due to VR and recommendations for action are discussed.Almost all patients and relatives had an understanding of the VR and generally considered them to be (very) good. This is consequently considering the aim and reason for the VR was to protect these groups of people from infection, among other things. Nevertheless, the consequences of the VR had an impact on the mental conditions of patients and relatives. The collected data show that patients and relatives felt the psychological distress due to VR comparable to the general psychological distress they were exposed to in the actual situation. Both parameters, “general psychological distress” and “psychological distress due to VR” correlate only slightly with each other. The low variance resolution indicates that the VR is an additional stressor that is largely independent of other parameters. Consequently, VR places additional stress on the mental status of patients and relatives, as described by Meesters, among others, in mothers of infants .Since the study presented here is cross-sectional, no concrete statements can be made about the medium- and long-term consequences among the respondents. In addition, the psychological distress due to VR was not assessed qualitatively. But based on the fact that elective procedures were severely restricted during the study period as part of the provision of ICU capacity in the context of the COVID-19 pandemic, it can be assumed that patients were confronted with more serious medical conditions . The impact of VR during the COVID-19 pandemic on the wellbeing of hospitalized patients and their visitors, particularly in vulnerable populations, was examined by Inees et al. . OverallWe suspect that the greater psychological distress on relatives results in part from the fact that they could not form their own impression of the patient's condition. It is known that inadequate information is a stressor for negative psychological effects such as posttraumatic stress symptoms, confusion, and anger . FurtherEven if VR contribute to a reduction of surgical site infections in postoperative patients , this doNo predictors of the severity of psychological distress were identified within the demographic parameters analyzed. Also, length of hospitalization, single or repeated hospitalization, or cause of hospitalization  did not provide information on the severity of psychological distress due to VR. Only the severity of physical limitations and/or the general psychological distress the patients were under, showed a small positive correlation with psychological distress due to VR. For this reason, all patients should be given the necessary attention and offered help in dealing with VR.via phone and social media. Consequently, direct physical contact and facial expressions/gestures were missed the most. While patients mentioned other interlocutors  as a possible alternative, the establishment of visiting rooms with protective measures  was most frequently desired by relatives. Video calls were used by only a few and were also mentioned as an alternative by only a few. We suspect that lack of experience, technical difficulty, and lack of access to a device are barriers. However, unsuitability for patients, e.g., due to sedation, could also be a reason  and their relatives .Since the Corona case numbers in the federal state, where the investigation was performed (Mecklenburg-Vorpommern) during the study period were rather low compared to other federal states , it can be assumed that the psychological distress of patients and their relatives was even higher in risk areas. Further research is needed to take targeted measures to benefit the mental health of patients and relatives during pandemic periods.The survey was successfully conducted prospectively on a large cohort, despite the difficult baseline conditions, even for the study investigators. The service volumes and elective procedures were reduced at some hospitals during the survey period. The high number of oncological patients may be explained first by the fact that the study was led by the Department of Hematology, Oncology and Palliative Medicine (bias). Second, the treatments of these patients cannot be electively discharged. At the same time, this represents a strength, since specifically oncological patients were affected by VR.Due to the involvement of a large number of clinics in the survey and the applicable contact restrictions, it was not possible to record exactly how many patients refused to participate, despite the coding of the questionnaires. A statement on the response rate is therefore not possible. As a result, a bias of the answers in the direction of socially desirable answers cannot be ruled out.To keep the questionnaire and the interview duration short despite the complexity of the survey (aim: to increase the number of participants), only a visual analog scale and no standard psychological questionnaires were used to record psychological stress. As a consequence, no statements can be made about qualitative psychological stress. Whether and to what extent the visit restrictions had serious health consequences and which coping strategies were used should be investigated in further studies. Whether and to what extent the patients/relatives used psychotherapeutic services was not recorded and represents a further limitation of this study.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee of the University of Rostock. The patients consented to participate in the study by filling out the questionnaire. The relatives verbally agreed to be interviewed before the interview.SF and CJ: conception of the work, data analysis and interpretation, and drafting the article. UK: conception of the work, data collection, and drafting the article. CSe: conception of the work and data collection. BK: data collection and head of study office. TH, FB, DS, CSc, and D-LD: data collection and critical revision of the article. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.