A volatile from the skin microbiota of flavivirus-infected hosts promotes mosquito attractiveness.

The host-seeking activity of hematophagous arthropods is essential for arboviral transmission. Here, we demonstrate that mosquito-transmitted flaviviruses can manipulate host skin microbiota to produce a scent that attracts mosquitoes. We observed that Aedes mosquitoes preferred to seek and feed on mice infected by dengue and Zika viruses. Acetophenone, a volatile compound that is predominantly produced by the skin microbiota, was enriched in the volatiles from the infected hosts to potently stimulate mosquito olfaction for attractiveness. Of note, acetophenone emission was higher in dengue patients than in healthy people. Mechanistically, flaviviruses infection suppressed the expression of RELMα, an essential antimicrobial protein on host skin, thereby leading to the expansion of acetophenone-producing commensal bacteria and, consequently, a high acetophenone level. Given that RELMα can be specifically induced by a vitamin A derivative, the dietary administration of isotretinoin to flavivirus-infected animals interrupted flavivirus life cycle by reducing mosquito host-seeking activity, thus providing a strategy of arboviral control.

The development of a parent report instrument of early communication and language skills of infants and toddlers in mainland China.

OBJECTIVE: This study was designed to produce a new parent-report measure, the Diagnostic Receptive Expressive Assessment of Mandarin-Infant Toddler Assessment of Communication and Language (DREAM-IT) in order to provide norms for the developmental skills of children aged 0-36 months in four areas: expressive language, receptive language, cognitive play and social skills. METHODOLOGY: The scale was designed to be both broader and deeper than existing instruments that neglect one or more of these significant domains involved in early language. Items were chosen by a group of specialists with clinical experience working with the age group and with attention to the developmental literature. Caregivers were tested individually by a trained person who asked the questions and provided examples. In addition to an extensive health questionnaire, caregivers answered questions in Mandarin about their child's behaviour using a scale of 'not yet', 'sometimes' or 'always' or listing out words and/or sounds understood or said by the child. The 476 participating caregivers were recruited at maternal and child healthcare clinics centred in Chengdu, China, 191 of whom were tested a second time seven months later. The children were sampled in three-month age-bands from 0 to 36 months. The sample was balanced for child gender by age band, and parental education was balanced. Caregivers of 0-24-month-old children and caregivers of 12-36 months were each asked a different set of questions, to determine the appropriate age range and cutoff points for each question, requiring the sample size to be doubled for children aged 12-24 months. RESULTS: The results were subject to item-response theory analysis to remove outlying items, and the resulting internal reliability was high for each domain (average Cronbach's alpha=0.87). The final instrument (between 67 and 113 questions in total) was refined to include the least redundant questions that had the highest intercorrelations, with attention paid to coverage of all domains across the age range. Two scales were developed: one for children 0-18 months, the second for children aged 18-36 months. The longitudinal design permitted the creation of growth curves and norms for each domain for six-month intervals from 0 to 36 months. A small sample of 32 parents of children with Down syndrome aged 18-36 months provided validation that the scales are highly sensitive to developmental delay. CONCLUSION: The instrument shows considerable promise for detecting early communication problems in children in China. WHAT THIS PAPER ADDS: What is already known on the subject In China, efforts were made in recent years to develop language assessments for infants and toddlers, but limitations existed with the domains included and number of items included per age group. Many clinical practitioners also continued to rely on language subtests of general developmental scales, which were limited in depth and breadth of language skills tested and were never intended for diagnosis of language delay. What this paper adds to existing knowledge This paper discusses the development of a valid caregiver report instrument for early communication and language skills of infants and toddlers in mainland China. The Diagnostic Receptive Expressive Assessment of Mandarin-Infant Toddler (DREAM-IT) includes foundational domains necessary for language and communication development in young children (receptive language, expressive language, cognitive play and social communication domains). The results show strong internal reliability (Cronbach's alpha) for each domain on a sample of 716 children sampled in three-month age bands from 0 to 36 months. The external validity proved strong when tested on a group of 32 young children with Down syndrome. What are the potential or actual clinical implications of this work? Besides helping to inform the diagnosis of language delays in infants and toddlers in China, the caregiver report instrument has special features to support clinical practitioners in a field that is just emerging in China. The unique support features include the automatic generation of a profile of relative strengths and weaknesses of the child on the report and the recommendation of child-specific caregiver coaching videos on a companion app.

Effects of osteopontin-enriched formula on lymphocyte subsets in the first 6 months of life: a randomized controlled trial.

BackgroundHuman milk is rich in osteopontin (OPN), which has immunomodulatory functions.MethodsIn a randomized controlled trial, standard formula (SF) and the same formula with 65 mg of OPN/L (F65) or 130 mg of OPN/L (F130), representing ~50 and 100% of the OPN concentration in human milk, were compared. We examined frequencies and composition of peripheral blood immune cells by four-color immunoflow cytometry of formula-fed infants at ages 1, 4, and 6 months, and compared them with a breastfed (BF) reference group.ResultsThe F130 group had increased T-cell proportions compared with the SF (P=0.036, average effect size 0.51) and F65 groups (P=0.008, average effect size 0.65). Compared with the BF group, the monocyte proportions were increased in the F65 (P=0.001, average effect size 0.59) and F130 (P=0.006, average effect size 0.50) groups, but were comparable among the formula groups.ConclusionOPN in an infant formula at a concentration close to that of human milk increased the proportion of circulating T cells compared with both SF and formula with added OPN at ~50% of the concentration in human milk. This suggests that OPN may favorably influence immune ontogeny in infancy and that the effects appear to be dose-dependent.

Growth, Nutrition, and Cytokine Response of Breast-fed Infants and Infants Fed Formula With Added Bovine Osteopontin.

OBJECTIVES: Breast milk contains a high concentration of osteopontin (OPN), a protein having multiple functions. In contrast, infant formula is low in OPN. A randomized clinical trial was performed to evaluate effects of adding a highly enriched bovine OPN fraction to formula, and infants whose mothers had already decided not to breast-feed were recruited. They were fed regular formula (F0) or the same formula with bovine OPN at 65 (F65) or 130 (F130) mg/L (50% and 100% of human milk level, respectively) from 1 to 6 months of age and were compared with a reference group of breast-fed (BF) infants. METHODS: Morbidity was recorded daily and 3-day dietary records collected monthly. Anthropometry was assessed monthly, and blood samples were taken at 1, 4, and 6 months of age. Hematology and iron status, serum cytokines, plasma amino acids, and blood urea nitrogen were analyzed. RESULTS: Formulas were well tolerated and there were no significant differences in formula intake or growth among the formula-fed groups. The F130 group had significantly lower plasma threonine than the F0 and F65 groups, and significantly lower plasma branched-chain amino acids (BCAAs) than the F0 group and, thus, was closer to BF infants. Plasma TNF-α was higher in formula-fed infants than in BF infants. Among the formula-fed groups, the proinflammatory cytokine TNF-α was significantly lower in the F65 and F130 groups than in the F0 group, suggesting that OPN downregulates inflammatory cytokines and thus affects immune function. CONCLUSIONS: Addition of OPN to infant formula changes amino acid metabolism and cytokine responses of FF infants and makes them more similar to BF infants. The lower prevalence of pyrexia in the F130 infants than in F0 infants suggests that adding OPN may confer health benefits.

Longitudinal Development of Infant Complementary Diet Diversity in 3 International Cohorts.

OBJECTIVES: To evaluate international differences in the development of minimum dietary diversity (MDD) between 6 and 12 months of age. STUDY DESIGN: Breastfed infants (115, 100, and 109 in Shanghai, Cincinnati, and Mexico City, respectively) were enrolled near birth and dietary intake assessed weekly by 24-hour recall of food frequency. Diet diversity per month from age 6-12 months was assessed as at least 4 of 7 food groups provided on the previous day. RESULTS: Across all cohorts, dietary diversity increased from 6 (31%) to 12 (92%) months of age. Shanghai infants were significantly more likely to achieve MDD than the other cohorts at each month of age. Meat/seafood accounted for a higher proportion of infant feeds in Shanghai compared with the other cohorts, and eggs were only fed in Shanghai, and proportional intake of dairy, grains, and fruit were highest in Cincinnati. Only 28% of Cincinnati infants fed >50% human milk achieved MDD between 6 and 12 months. CONCLUSIONS: The proportion of infants between 6 and 12 months achieving MDD was significantly higher in Shanghai than in Mexico City or Cincinnati at all ages. Of particular concern was low dietary diversity among highly breastfed Cincinnati cohort infants, suggesting a need for greater education of breastfeeding mothers about the need to introduce a diverse complementary food diet.

Mechanism of Vaginal Epithelial Cell Pyroptosis Induced by the NLRP3 Inflammasome in Vulvovaginal Candidiasis.

PROBLEM: Vulvovaginal candidiasis (VVC) is a common mucosal fungal infection, and Candida albicans is the main causative agent. The NLRP3 inflammasome plays an important role in VVC, but the underlying mechanism is unknown. METHOD OF STUDY: Vaginal epithelial cells were divided into three groups: control, C. albicans strain SC5314 (wild-type, WT), and WT+ Matt Cooper Compound 950 (MCC950, a specific NLRP3 inhibitor). After human vaginal epithelial cells were pretreated with 1 µmol/L MCC950 for 2 h, C. albicans (MOI = 1) was cocultured with the human vaginal epithelial cells for 12 h. The cell supernatants were collected, LDH was detected, and the IL-1ß and IL-18 levels were determined by ELISA. The expression of the pyroptosis-related proteins NLRP3, Caspase-1 p20 and GSDMD was measured by Western blotting analysis. The protein expression of the pyroptosis-related N-terminus of GSDMD (GSDMD-N) was detected by immunofluorescence. RESULTS: In this study, we showed that the WT C. albicans strain induced pyroptosis in vaginal epithelial cells, as indicated by the LDH and proinflammatory cytokine levels and the upregulated levels of the pyroptosis-related proteins NLRP3, Caspase-1 p20, and GSDMD-N. MCC950 reversed the changes in the expression of these proteins and proinflammatory cytokines in vaginal epithelial cells. CONCLUSION: C. albicans activated the NLRP3 inflammasome to induce vaginal epithelial cell pyroptosis. MCC950 inhibited the NLRP3 inflammasome, reduced vaginal epithelial cell pyroptosis, and decreased the release of inflammatory cytokines.

Assessing the usefulness of the Little Developmental Coordination Disorder Questionnaire-Chinese in Chinese preschoolers: a sex-and age-specific analysis.

Aim: This study evaluated the sex-and age-specific usefulness of the Little Developmental Coordination Disorder Questionnaire-Chinese (LDCDQ-CH) in Chinese preschoolers. Method: A population-based sample of 51,110 children aged 3-5 years was recruited. Internal reliability, construct validity, concurrent validity with the Ages and Stages Questionnaire-third edition (ASQ-3), and discriminant validity with the Movement Assessment Battery for Children-second edition (MABC-2) were assessed. Age and sex effects on LDCDQ-CH scores were analyzed using ANOVA and t-tests. Results: The LDCDQ-CH exhibited excellent internal consistency and reliability across ages and genders. Confirmatory factor analysis supported the 15-item model's satisfactory fit. Positive and significant correlations were observed between LDCDQ-CH and ASQ-3 scores, indicating robust concurrent validity. Significant associations were found between LDCDQ-CH and MABC-2 scores. Higher scores were observed in older children and girls, indicating age- and sex-related differences in motor functional performance. Conclusion: The LDCDQ-CH is a reliable and valid tool to support early identification of motor coordination difficulty in Chinese preschoolers, and guiding interventions. Findings support its use across ages and genders, highlighting its potential in the Chinese context. Age- and sex-specific norms are needed for enhanced clinical applicability.

Advancing stroke therapy: the potential of MOF-based nanozymes in biomedical applications.

In this study, we explored the growing use of metal-organic framework (MOF)-based Nanozymes in biomedical research, with a specific emphasis on their applications in stroke therapy. We have discussed the complex nature of stroke pathophysiology, highlighting the crucial role of reactive oxygen species (ROS), and acknowledging the limitations of natural enzymes in addressing these challenges. We have also discussed the role of nanozymes, particularly those based on MOFs, their structural similarities to natural enzymes, and their potential to improve reactivity in various biomedical applications. The categorization of MOF nanozymes based on enzyme-mimicking activities is discussed, and their applications in stroke therapy are explored. We have reported the potential of MOF in treating stroke by regulating ROS levels, alleviation inflammation, and reducing neuron apoptosis. Additionally, we have addressed the challenges in developing efficient antioxidant nanozyme systems for stroke treatment. The review concludes with the promise of addressing these challenges and highlights the promising future of MOF nanozymes in diverse medical applications, particularly in the field of stroke treatment.

Specific infant feeding practices do not consistently explain variation in anthropometry at age 1 year in urban United States, Mexico, and China cohorts.

Infant feeding practices generally influence infant growth, but it is unclear how introduction of specific foods affects growth across global populations. We studied 3 urban populations in the Global Exploration of Human Milk study to determine the association between infant feeding and anthropometry at 1 y of age. Three hundred sixty-five breastfeeding mother-infant pairs (120 US, 120 China, and 125 Mexico) were recruited soon after the infant's birth. Enrollment required agreement to breastfeed ≥75% for at least 3 mo. Weekly, 24-h, food frequency data were conducted on infants for 1 y and exclusive breastfeeding (EBF) duration and timing of specific complementary food introduction were calculated. Weight and length were measured at age 1 y and anthropometry Z-scores calculated using WHO standards. Cohorts in the 3 urban populations (Shanghai, China; Cincinnati, USA; and Mexico City, Mexico) differed by median EBF duration (5, 14, and 7 wk, respectively; P < 0.001), timing of introduction of meat/eggs/legumes (4.8, 9.3, and 7.0 mo, respectively; P < 0.0001), and other feeding practices. By age 1 y, infants in Shanghai were heavier and longer than Cincinnati and Mexico City infants (P < 0.001). Adjusting for nonfeeding covariates, the only feeding variable associated with anthropometry was EBF duration, which was modestly inversely associated with weight-for-age but not length-for-age or BMI Z-scores at 1 y. Although feeding variables differed by cohort, their impact on anthropometry differences was not consistent among cohorts. Overall, across these urban, international, breast-fed cohorts, differences in specific feeding practices did not explain the significant variation in anthropometry.

Glycolipid metabolic status of overweight/obese adolescents aged 9- to 15-year-old and the BMI-SDS/BMI cut-off value of predicting dyslipidemiain boys, Shanghai, China: a cross-sectional study.

BACKGROUND: The prevalence of adolescents' obesity and overweight has dramatically elevated in China. Obese children were likely to insulin resistance and dyslipidemia, which are risk factors of cardiovascular diseases. However there was no cut-off point of anthropometric values to predict the risk factors in Chinese adolescents. The present study was to investigate glycolipid metabolism status of adolescents in Shanghai and to explore the correlations between body mass index standard deviation score (BMI-SDS) and metabolic indices, determine the best cut-off value of BMI-SDS to predict dyslipidemia. METHODS: Fifteen schools in Shanghai's two districts were chosen by cluster sampling and primary screening was done in children aged 9-15 years old. After screening of bodyweight and height, overweight and obese adolescents and age-matched children with normal body weight were randomly recruited in the study. Anthropometric measurements, biochemical measurements of glycolipid profiles were done. SPSS19.0 was used to analyze the data. Receiver operating characteristic (ROC) curves were made and the best cut-off values of BMI-SDS to predict dyslipidemia were determined while the Youden indices were maximum. RESULTS: Five hundred and thirty-eight adolescents were enrolled in this research, among which 283 have normal bodyweight, 115 were overweight and 140 were obese. No significant differences of the ages among 3 groups were found. There were significant differences of WC-SDS (p<0.001), triacylglycerol (p<0.05), high and low density lipoprotein cholesterol (p<0.01), fasting insulin (p<0.01) and C-peptide (p<0.001) among 3 groups. Significant difference of fasting glucose was only found between normal weight and overweight group. Significant difference of total cholesterol was found between obese and normal weight group. There was no significant difference of glycated hemoglobin among 3 groups. The same tendency was found in boys but not in girls. Only HDL-C reduced and TG increased while BMI elevated in girls. The best cut-off value of BMI-SDS was 1.22 to predict dyslipidemia in boys. The BMI cut-off was 21.67 in boys. CONCLUSION: Overweight and obese youths had reduced insulin sensitivity and high prevalence of dyslipidemia.When BMI-SDS elevated up to 1.22 and BMI was higher than 21.67 in boys, dyslipidemia may happen.

Downregulated APOD and FCGR2A correlates with immune infiltration and lipid-induced symptoms of irritable bowel syndrome.

Fat intake is among the most significant triggers for symptom development in patients with irritable bowel syndrome (IBS). Nevertheless, long-term restriction in fatty foods ingestion may lead to nutritional inadequacies. This study aimed to identify the crucial genes involved in lipid-induced gastrointestinal symptoms, contributing to helping IBS patients regulate fat. The clinical characteristics of the subjects were collected by questionnaire investigation and analyzed using multivariate logistic regression. Differentially expressed genes (DEG) and signaling pathways were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. ImmuInfiltration and CIBERSORT packages evaluated small intestine immune cell infiltration. Random forest and SVM-RFE algorithms were used to select hub genes. A receiver operating characteristic curve was used to access the diagnostic significance of each hub gene. Gene Set Enrichment Analysis (GSEA) was performed to identify hub genes' molecular processes in IBS development after lipid infusion. IBS patients' risk, severity, and quality of life increased with fat intake. In total, 116 robust DEGs were identified in IBS patients after lipid infusion using the GSE166869 dataset and were mainly clustered in the immune and inflammatory pathways. IBS patients had greater Neutrophils, CD4+ T cells, and M1 Macrophages than healthy controls. Furthermore, infiltration levels of Neutrophils and resting memory CD4+ T cells were inversely related to the expression of hub genes (IGKV1D-43, IGKV1-12, APOD, FCGR2A and IGKV2-29). After lipid infusion, GSEA results of each hub gene indicated the relevance of proinflammatory pathways in IBS pathogenesis. After verification, only APOD and FCGR2A were stably downregulated in small intestinal mucosa and plasma of IBS patients. The area under the curve of APOD combined with FCGR2A expression was 0.9. APOD and FCGR2A may be promising biomarkers for IBS diagnosis and lipid-sensitive IBS patients. Their potential roles in the immune microenvironment of the small intestinal mucosa may provide a vital clue to IBS precision therapy.

Is lymphatic invasion of microrectal neuroendocrine tumors an incidental event?: A case report.

BACKGROUND: A rectal neuroendocrine tumor (rNET) is a malignant tumor originating from neuroendocrine cells. Currently, tumor size is the primary basis for assessing tumor risk. CASE SUMMARY: This article reports the case of a 46-year-old male patient who underwent a colonoscopy that found a 3 mm rectal polypoid bulge. The pathological examination of a sample collected with biopsy forceps revealed a neuroendocrine tumor. Further endoscopic submucosal dissection rescue therapy was used. The presence of lymphatic vessels indicated that the tumor had infiltrated the negative resection margin. The lesion was located in the distal rectum near the anal canal. Therefore, to ensure the patient's quality of life, follow-up observation was conducted after full communication with the patient. No tumor recurrence or distant metastasis has been found during the 13-mo follow-up after surgery. CONCLUSION: Despite the presence of lymphatic invasion and extremely small diameter rNETs in our case, this phenomenon may not imply a higher risk of distant lymph node and organ metastasis.

Impact of Newborn Screening Programme for Congenital Heart Disease in Shanghai: a five-year observational study in 801,831 newborns.

Background: Newborn Screening Programme for Congenital Heart Disease (CHD) in Shanghai has been in operation for over 5 years, and its feasibility and effectiveness still lack a systematic and comprehensive evaluation. This study aimed to detail the implementation of the programme and evaluate its results, benefits, and reliability in clinical practice. Methods: This study was an observational study involving all newborns received CHD screening in Shanghai from 2017 to 2021. Pulse oximetry (POX) plus cardiac murmur auscultation (namely the dual-index method) was used for CHD screening in newborns aged 6-72 h. Newborns who screened positive was recommended for echocardiography, and those diagnosed with CHD would be planned for further evaluation and intervention. Data were aggregated by birth year and district of birth. Results of neonatal CHD screening, diagnosis and treatment, and temporal trends of infant mortality rate (IMR) and the proportion of under-five mortality (U5M) attributed to CHD were analysed. A retrospective cohort study was also conducted to assess the reliability of the dual-index method in clinical practice. Findings: In total, 801,831 (99.48%) newborns were screened for CHD, 16,489 (2.06%) were screened positive, and 3541 (21.47%) of the screened-positive newborns were identified with CHD. Seven hundred and fifty-two patients with CHD received surgical or interventional treatment with a successful rate of 94.81%. The period from 2015 to 2021 witnessed an approximately twofold decrease in IMR from 4.58‰ to 2.30‰, and a downtrend in the proportion of U5M attributed to CHD from 25.93% to 16.61%. High sensitivity and specificity of the dual-index method in clinical practice were observed for both critical (100.00% and 97.72%) and major CHD (98.47% and 97.76%). Interpretation: Newborn screening programme for CHD has been well implemented in Shanghai, and this programme is a successful public health intervention to reduce infant death. Our study provides encouraging evidence and experience for implementing newborn screening programme for CHD nationwide in China. Funding: This study was supported by the National Key Research and Development Programme of China (2021YFC2701004 and 2016YFC1000506), CAMS Innovation Fund for Medical Sciences (2019-I2M-5-002), and Three-Year Planning for Strengthening the Construction of Public Health System in Shanghai (No. GWIV-24).

Comparison of characteristics between true rectal neuroendocrine tumors and rectal hyperplastic polyps among patients with endoscope-diagnosed rectal neuroendocrine tumors.

Background: To explore the white light endoscopy and endoscopic ultrasonography (EUS) features of rectal hyperplastic polyps (rHP) misdiagnosed as rectal neuroendocrine neoplasms (rNENs). In rNENs with a diameter of 5-10 mm, the endoscopic findings are not typical and some of them are similar to rHP, so it is not uncommon to misdiagnose rNENs as rHP. However, misdiagnosis of rHP as rNENs has not been reported in the literature, which can alert clinicians to the existence of this possibility and avoid over-treatment. Methods: We collected 245 cases of rectal submucosal tumor (SMT) diagnosed by endoscopy in our hospital from January 2015 to December 2020 and 103 patients with suspected rNENs identified through endoscopy. A retrospective analysis was conducted of the shape, color, vascular dilatation, and boundary on the surface of the lesion under white light endoscope, and the source, boundary, and echo characteristics of EUS. We also analyzed the endoscopic features of rHP misdiagnosed as rNENs. Endoscopic diagnosis and pathological diagnosis were reviewed by a senior endoscopic expert and pathologist respectively. The counting data were tested and analyzed by χ2 test and Fisher exact probability method. Results: A total of 103 cases of rNENs were diagnosed by endoscope, among whom 75 cases were confirmed as rNENs (72.8%) and 8 cases as rHP (7.8%) by histopathology. There was no significant difference between rNENs and rHP in terms of gender, age, clinical manifestation, shape and color of lesions, dilatation of blood vessels on the surface, and location of lesions. Meanwhile, there were significant differences in whether the boundary of the lesion was clear under white light endoscopy, and the source, echo, and boundary of the lesion under EUS. Conclusions: The morphology of some rHP is similar to rNENs under endoscopy. The boundary is clear under white light endoscopy and the source, echo, and boundary under EUS are helpful for the diagnosis of rNENs and rHP.

Metabolic Phenotype and Microbiome of Infants Fed Formula Containing Lactobacillus paracasei Strain F-19.

Early childhood nutrition drives the development of the gut microbiota. In contrast to breastfeeding, feeding infant formula has been shown to impact both the gut microbiota and the serum metabolome toward a more unfavorable state. It is thought that probiotics may alter the gut microbiota and hence create a more favorable metabolic outcome. To investigate the impact of supplementation with Lactobacillus paracasei spp. paracasei strain F-19 on the intestinal microbiota and the serum metabolome, infants were fed a formula containing L. paracasei F19 (F19) and compared to a cohort of infants fed the same standard formula without the probiotic (SF) and a breast-fed reference group (BF). The microbiome, as well as serum metabolome, were compared amongst groups. Consumption of L. paracasei F19 resulted in lower community diversity of the gut microbiome relative to the SF group that made it more similar to the BF group at the end of the intervention (4 months). It also significantly increased lactobacilli and tended to increase bifidobacteria, also making it more similar to the BF group. The dominant genus in the microbiome of all infants was Bifidobacterium throughout the intervention, which was maintained at 12 months. Although the serum metabolome of the F19 group was more similar to the group receiving the SF than the BF group, increases in serum TCA cycle intermediates and decreases in several amino acids in the metabolome of the F19 group were observed, which resulted in a metabolome that trended toward the BF group. Overall, L. paracasei F19 supplementation did not override the impact of formula-feeding but did impact the microbiome and the serum metabolome in a way that may mitigate some unfavorable metabolic impacts of formula-feeding.

Therapeutic strategy analysis of patients with advanced stage high-grade neuroendocrine cervical cancer: A real-world multicenter study.

OBJECTIVE: To explore the management of high-grade neuroendocrine cervical cancer (HGNECC) since there has been no standard treatment for it. METHODS: Data on the management of HGNECC were retrospectively analyzed. Patients with FIGO stage IIB to IVB HGNECC from six hospitals were enrolled. The Kaplan-Meier method was used for survival analysis. Prognostic factors were determined using a Cox proportional-hazards regression model. RESULTS: A total of 43 patients were included in the study. The multivariate analysis showed that chemotherapy was the preferred treatment as it improved progression-free survival (PFS; P = 0.008) and overall survival (OS; P = 0.005). Distance metastasis was a significant negative prognostic factor for OS (P = 0.002), while radical surgery was a significant positive prognostic factor for PFS (P = 0.05). Compared with those who had received cisplatin and etoposide (≥5 cycles), patients who had received paclitaxel plus platinum-based chemotherapy showed better PFS and OS. Five patients (two at stage IIB and three at stage IV) showed relatively long-term survival. Of these patients, four had undergone radical surgery including tumor-debulking, while three also received adjuvant chemotherapy. CONCLUSION: Paclitaxel plus cisplatin or paclitaxel plus carboplatin may be more effective than etoposide plus cisplatin. Radical surgery followed by chemotherapy may be a favorable alternative intervention for selected patients with advanced stage cancer.

Validation of diagnostic strategies of autoimmune atrophic gastritis: A case report.

BACKGROUND: Autoimmune atrophic gastritis (AAG) is a type of chronic gastritis that mainly affects the gastric corpus. Due to the lack of standard diagnostic criteria and overlaps with the courses of Helicobacter pylori-related atrophic gastritis, reports on the diagnostic strategy of AAG at an early stage are limited. CASE SUMMARY: A 71-year-old woman with severe anemia was diagnosed with AAG. Endoscopic views and pathological findings showed the coexistence of normal mucosa in the gastric antrum and atrophic mucosa in the gastric fundus. Serological tests showed that anti-parietal cell antibodies and anti-intrinsic factor antibodies were both positive. Immunohistochemical results, which showed negative H+-K+ ATPase antibody staining and positive chromogranin A (CgA) staining, confirmed the mechanism of this disease. After vitamin B12 and folic acid supplementation, the patient recovered well. CONCLUSION: Successful diagnosis of AAG includes serological tests, endoscopic characteristics, and immunohistochemistry for H+-K+ ATPase and CgA antibodies.

Serum cytokine patterns are modulated in infants fed formula with probiotics or milk fat globule membranes: A randomized controlled trial.

BACKGROUND: Proteins and lipids of milk fat globule membrane (MFGM) and probiotics are immunomodulatory. We hypothesized that Lactobacillus paracasei ssp. paracasei strain F19 (F19) would augment vaccine antibody and T helper 1 type immune responses whereas MFGM would produce an immune response closer to that of breastfed (BF) infants. OBJECTIVE: To compare the effects of supplementing formula with F19 or bovine MFGM on serum cytokine and vaccine responses of formula-fed (FF) and BF infants. DESIGN: FF infants were randomized to formula with F19 (n = 195) or MFGM (n = 192), or standard formula (SF) (n = 194) from age 21±7 days until 4 months. A BF group served as reference (n = 208). We analyzed seven cytokines (n = 398) in serum at age 4 months using magnetic bead-based multiplex technology. Using ELISA, we analyzed anti-diphtheria IgG (n = 258) and anti-poliovirus IgG (n = 309) concentrations in serum before and after the second and third immunization, respectively. RESULTS: Compared with SF, the F19 group had greater IL-2 and lower IFN-γ concentrations (p<0.05, average effect size 0.14 and 0.39). Compared with BF, the F19 group had greater IL-2, IL-4 and IL-17A concentrations (p<0.05, average effect size 0.42, 0.34 and 0.26, respectively). The MFGM group had lower IL-2 and IL-17A concentrations compared with SF (p<0.05, average effect size 0.34 and 0.31). Cytokine concentrations were comparable among the MFGM and BF groups. Vaccine responses were comparable among the formula groups. CONCLUSIONS: Contrary to previous studies F19 increased IL-2 and lowered IFN-γ production, suggesting that the response to probiotics differs across populations. The cytokine profile of the MFGM group approached that of BF infants, and may be associated with the previous finding that infectious outcomes for the MFGM group in this cohort were closer to those of BF infants, as opposed to the SF group. These immunomodulatory effects support future clinical evaluation of infant formula with F19 or MFGM.

Milk Fat Globule Membrane as a Modulator of Infant Metabolism and Gut Microbiota: A Formula Supplement Narrowing the Metabolic Differences between Breastfed and Formula-Fed Infants.

SCOPE: Milk fat globule membrane (MFGM) is an important component of milk that has previously been removed in the manufacture of infant formulas, but has recently gained attention owing to its potential to improve immunological, cognitive, and metabolic health. The goal of this study is to determine whether supplementing MFGM in infant formula would drive desirable changes in metabolism and gut microbiota to elicit benefits observed in prior studies. METHODS AND RESULTS: The serum metabolome and fecal microbiota are analyzed using 1 H NMR spectroscopy and 16S rRNA gene sequencing respectively in a cohort of Chinese infants given a standard formula or a formula supplemented with an MFGM-enriched whey protein fraction. Supplementing MFGM suppressed protein degradation pathways and the levels of insulinogenic amino acids that are typically enhanced in formula-fed infants while facilitating fatty acid oxidation and ketogenesis, a feature that may favor brain development. MFGM supplementation did not induce significant compositional changes in the fecal microbiota but suppressed microbial diversity and altered microbiota-associated metabolites. CONCLUSION: Supplementing MFGM in a formula reduced some metabolic gaps between formula-fed and breastfed infants.

Preferred method of therapy for patients with early-stage high-grade neuroendocrine carcinoma of the cervix.

High-grade neuroendocrine carcinoma of the uterine cervix (HGNECC) is a rare and overly aggressive malignancy. Due to its rarity, there is no standard treatment. A majority of early-stage patients receive radical hysterectomy and lymph node dissection (RH+LND), followed by adjuvant chemotherapy. To explore the most suitable methods of therapy, a multicenter retrospective review of HGNECC patients was conducted. A total of 133 patients (I-IIA, FIGO 2009) treated from March 2003 to September 2018 were enrolled in this study. The 5-year DFS and OS rates for stages IB and IIA were 44.8% and 39.5%, and 53.8% and 39.6%, respectively. The median DFS and OS for stages IB and IIA were 41 months and 12 months, and 63 months and 45 months, respectively. The RH+LND surgery procedure was associated with a significantly better DFS (P=0.015) and OS (P=0.006), while the bilateral salpingo-oophorectomy (BSOE) was also associated with a better OS (P=0.023). The efficacy of paclitaxel-platinum (TP/C) adjuvant chemotherapy regimens need to be confirmed using clinical trials, especially for tumors with a diameter of >4 cm (P=0.0005). Therefore, the RH+LND+BSOE procedure was recommended for HGNECC patients at stages IB-IIA. TP/C is an alternative chemotherapy regimen that results in optimal survival. Moreover, a tumor diameter of >4 cm, LNM, DSI, and LVSI were confirmed as high-risk factors for worse DFS and OS. Patients without risk factor, 1 or 2 or 3 risk factors, and 4 risk factors had significantly different DFS and OS values.