Objective: To establish the reference values and growth curves of length for weight and head circumference for weight among Chinese newborns in order to provide a reference for the assessment of body proportionality at birth. Methods: A cross-sectional design was applied. A total of 24 375 singleton live birth newborns with gestational ages at birth of 24⁺⁰ to 42⁺⁶ weeks were recruited from June 2015 to November 2018 from 13 cities including Beijing, Harbin, Xi'an, Shanghai, Nanjing, Wuhan, Guangzhou, Fuzhou, Kunming, Tianjin, Shenyang, Changsha, and Shenzhen, excluding those with maternal or newborn conditions that may impact the establishment of the reference values. The generalized additive model for location, scale, and shape was employed to establish reference values in terms of percentile and growth curves of length for weight and head circumference for weight for male and female newborns. The random forest machine learning method was employed to analyze the importance of variables between the established reference values in this study and the previous published weight/length, body mass index (BMI), ponderal index (PI), weight/head circumference, length/head circumference in the assessment of symmetrical and asymmetrical small for gestational age (SGA) newborns. Results: A total of 24 375 newborns with 13 197 male infants (preterm birth 7 042 infants and term birth 6 155 infants) and 11 178 female infants (preterm birth 5 222 infants and term birth 5 956 infants) were included in this study. The reference values in terms of percentile (P₃, P₁₀, P₂₅, P₅₀, P₇₅, P₉₀, P₉₇) and growth curves of length for weight and head circumference for weight were obtained for male and female newborns with gestational ages of 24⁺⁰ to 42⁺⁶ weeks. The median birth lengths corresponding to the birth weights of 1 500, 2 500, 3 000, and 4 000 g were 40.4, 47.0, 49.3 and 52.1 cm for males and 40.4, 47.0, 49.2, and 51.8 cm for females, respectively; the median birth head circumferences were 28.4, 32.0, 33.2 and 35.2 cm for males and 28.4, 32.0, 33.1, and 35.1 cm for females, respectively. The differences of length for weight between males and females were minimum, with the difference range of -0.3 to 0.3 cm at P₅₀; the differences of head circumference for weight between males and females were minimum, with the difference range of 0 to 0.2 cm at P₅₀. Based on the match between birth length and birth weight for classifying symmetrical and asymmetrical SGA, length for weight and PI contributed the most, accounting for 0.32 and 0.25, respectively; based on the match between birth head circumference and birth weight, head circumference for weight and weight/head circumference contributed the most, accounting for 0.55 and 0.12, respectively; based on the match between birth length or head circumference with birth weight, head circumference for weight and length for weight contributed the most, accounting for 0.26 and 0.21, respectively. Conclusion: The establishment of the new standardized growth reference values and growth curves of length for weight and head circumference for weight among Chinese newborns are useful for clinical practice and scientific research.
Female ; Humans ; Infant, Newborn ; Male ; Birth Weight ; Body Height ; China ; Cross-Sectional Studies ; East Asian People ; Fetal Growth Retardation ; Gestational Age ; Premature Birth ; Reference Values

Interleukin 6 (IL-6), an important component of cardiac microenvironment, favors cardiac repair by improving cardiomyocyte regeneration in different models. This study aimed to investigate the effects of IL-6 on stemness maintenances and cardiac differentiation of mouse embryonic stem cells (mESCs). The mESCs were treated with IL-6 for two days, and then subjected to CCK-8 essay for proliferation analysis and quantitative real-time PCR (qPCR) to evaluate the mRNA expression of genes related to stemness and germinal layers differentiation. Phosphorylation levels of stem cell-related signal pathways were detected by Western blot. siRNA was used to interfere the function of STAT3 phosphorylation. Cardiac differentiation was investigated by the percentage of beating embryoid bodies (EBs) and qPCR analysis of cardiac progenitor markers and cardiac ion channels. IL-6 neutralization antibody was applied to block the endogenous IL-6 effects since the onset of cardiac differentiation (embryonic day of 0, EB0). The EBs were collected on EB7, EB10 and EB15 to investigate the cardiac differentiation by qPCR. On EB15, Western blot was applied to investigate the phosphorylation of several signaling pathways, and immunochemistry staining was adopted to trace the cardiomyocytes. IL-6 antibody was administered for two days (short term) on EB4, EB7, EB10 or EB15, and percentages of beating EBs at late developmental stage were recorded. The results showed that exogenous IL-6 promoted mESCs proliferation and favored maintenances of pluripotency, evidenced by up-regulated mRNA expression of oncogenes (c-fos, c-jun) and stemness markers (oct4, nanog), down-regulated mRNA expression of germ layer genes (branchyury, FLK-1, pecam, ncam, sox17), and increased phosphorylation of ERK1/2 and STAT3. siRNA targeting JAK/STAT3 partially attenuated the effects of IL-6 on cell proliferation and mRNA expression of c-fos and c-jun. During differentiation, long term IL-6 neutralization antibody application decreased the percentage of beating EBs, down-regulated mRNA expression of ISL1, GATA4, α-MHC, cTnT, kir2.1, cav1.2, and declined the fluorescence intensity of cardiac α actinin in EBs and single cell. Long term IL-6 antibody treatment decreased the phosphorylation of STAT3. In addition, short term (2 d) IL-6 antibody treatment starting from EB4 significantly reduced the percentage of beating EBs in late development stage, while short term IL-6 antibody treatment starting from EB10 significantly increased the percentage of beating EBs on EB16. These results suggest that exogenous IL-6 promotes mESCs proliferation and favors stemness maintenance. Endogenous IL-6 regulates mESC cardiac differentiation in a development-dependent manner. These findings provide important basis for the study of microenvironment on cell replacement therapy, as well as a new perspective for understanding the pathophysiology of heart diseases.
Animals ; Mice ; Interleukin-6 ; Mouse Embryonic Stem Cells ; Cell Differentiation ; Proto-Oncogene Proteins c-fos ; RNA, Messenger

OBJECTIVE: Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery. METHODS: We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated. RESULTS: A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery. CONCLUSION These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.
Female ; Humans ; Male ; Middle Aged ; Brucellosis ; COVID-19 ; Retrospective Studies ; SARS-CoV-2 ; Treatment Outcome ; Case Reports as Topic

Objective: To construct growth standards for Chinese children under 7 years of age. Methods: Cross-sectional study design based on national representative data on children's growth and development in 2015 was used. Stratified cluster sampling method was used. A total of 83 628 healthy children aged 0-<7 years from 9 cities, including Beijing, Harbin, Xi'an, Shanghai, Nanjing, Wuhan, Guangzhou, Fuzhou, and Kunming, were investigated from June to November 2015, excluding those with adverse conditions that may impact the establishment of the growth standards. Weight, length (height) and head circumference were measured using unified measurement tools and measurement methods. The Lambda-Mu-Sigma method was employed to establish percentile and standard deviation score reference values of weight-for-age, length (height)-for-age, head circumference-for-age, weight-for-length (height) and body mass index (BMI)-for-age of the study population. The standard deviation score curves of the new-established growth standards were compared with the 2009 reference standards. Results: Reference values of percentile (P₃, P₁₀, P₂₅, P₅₀, P₇₅, P₉₀, P₉₇) and standard deviation score (-3, -2, -1, 0,+1,+2,+3) of weight-for-age, length (height)-for-age, head circumference-for-age, weight-for-length (height) and BMI-for-age were obtained. Compared with the 2009 growth standards, the difference of weight at P₅₀ was -0.1-0.4 kg, the difference of length (height) at P₅₀ was 0.1-1.3 cm, the difference of head circumference at P₅₀ was -0.2-0.2 cm, the difference of weight for length (height) at P₅₀ was -0.2-0.5 kg, and the difference of BMI at P₅₀ was -0.2-0.2 kg/m². The main differences were as follows: weight for girls aged 5.0-<7.0 years was 0.4-0.6 kg higher at +2 s, height for boys and girls aged 2.0-<7.0 years was 0.4-1.4 cm higher at -2 s, and BMI for boys and girls aged 5.0-<7.0 years was 0.1-0.3 kg/m² higher at +2 s than the 2009 reference standards. Conclusion: The newly established growth standards for Chinese children under 7 years of age that have achieved a minor revision to the 2009 reference standards, are recommended for nationwide use in growth monitoring and nutritional assessment.
Male ; Female ; Child ; Humans ; Infant ; Child Development ; Body Weight ; Cross-Sectional Studies ; East Asian People ; Body Height ; China/epidemiology* ; Reference Standards ; Reference Values ; Body Mass Index

Objective: To examine risk factors of simple obesity and their interaction in preschool children in China. Methods: A total of 63 292 preschool children aged 3-7 years selected by cluster random sampling in 9 cities of China, including Beijing, Harbin, Xi'an, Shanghai, Nanjing, Wuhan, Guangzhou, Fuzhou and Kunming, were investigated from June to November in 2016. Based on the BMI-for-age cut off points of overweight and obesity for Chinese children aged 2-18 years, a total of 1 522 obese children (1 006 boys and 516 girls) were screened. By population-based matched case-control design, a normal weight child was randomly selected to match with an obese child by sex, age (difference ≤6 months) and body height (difference ≤5 cm) from the survey area. Conditional logistic regression model was used to analyze association of risk factors with obesity and the interaction of risk factors. Results: ① Univariate conditional logistic regression model showed that 17 risk factors of simple obesity had statistical significance (P<0.001), including high birth weight, cesarean section, gestational diabetes, gestational hypertension, formula feeding in the first 6 months after birth, strong appetite, fast or slow eating speed, low intensity of outdoor activities, daily outdoor activity time <1 hour, daily screen viewing time < 1 hour or ≥2 hours, daily night sleep time <9 hours, mother overweight, father overweight, mother's low educational level, father's low educational level, non-nuclear family structure, and parents not being the primary caregivers of children. ②Multivariate conditional logistic regression model showed that 12 risk factors had statistical significance, including high birth weight (OR=1.83, 95%CI:1.29-2.61, P<0.001), cesarean section (OR=1.22, 95%CI:1.07-1.39, P=0.003), gestational diabetes (OR=4.57, 95%CI:2.13-9.79, P<0.001), mother's low educational level (OR=1.52, 95%CI:1.11-2.07, P=0.008), single parent family (OR=4.79, 95%CI:1.44-15.88, P=0.010), mother overweight (OR=2.58, 95%CI:1.93-3.46, P<0.001), father overweight (OR=2.40, 95%CI:1.86-3.10, P<0.001), strong appetite (OR=7.78, 95%CI:5.38-11.27, P<0.001), fast eating speed (OR=6.59, 95%CI:4.86-8.94, P<0.001), daily outdoor activity time <1 hour (OR=1.42, 95%CI: 1.09-1.85, P=0.009), daily night sleep time <9 hours (OR=1.59, 95%CI: 1.13-2.23, P=0.007), daily screen viewing time ≥2 hours (OR=1.69, 95%CI:1.27-2.24, P<0.001). ③ Interaction of the four groups of risk factors had statistical significance, including interaction between mother overweight and father overweight (OR=5.53, 95%CI: 3.76-8.13, P<0.001), interaction between strong appetite and fast eating speed (OR=54.48, 95%CI: 32.95-90.06, P<0.001), interaction between low intensity of outdoor activity and daily outdoor activity time <1 hour (OR=2.12, 95%CI: 1.29-3.48, P=0.002), interaction between daily night sleep time <9 hours and daily screen viewing time ≥2 hours (OR=2.83, 95%CI: 1.71-4.68, P<0.001). Conclusions: This study identified 12 risk factors of childhood obesity, including high birth weight, cesarean section, gestational diabetes, mother's low educational level, single parent family, mother overweight, father overweight, strong appetite, fast eating speed, daily short outdoor activity time, daily short night sleep time, daily long screen viewing time, and interaction of the four groups of risk factors had statistical significance, including strong interaction between mother overweight and father overweight, interaction between strong appetite and fast eating speed, interaction between low intensity of outdoor activity and daily short outdoor activity time, interaction between daily short night sleep time and daily long screen viewing time.
Adolescent ; Body Mass Index ; Cesarean Section ; Child ; Child, Preschool ; China/epidemiology* ; Cities/epidemiology* ; Female ; Humans ; Male ; Overweight/epidemiology* ; Pediatric Obesity/epidemiology* ; Pregnancy ; Prevalence ; Risk Factors

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

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

The study aims to investigate the effects of cardiac fibroblast (CF) paracrine factors on murine embryonic stem cells (ESCs). Conditioned mediums from either neonatal cardiac fibroblasts (ConM-NCF) or adult cardiac fibroblasts (ConM-ACF) were diluted by 1:50 and 1:5, respectively, to investigate whether these conditioned mediums impact murine ESCs distinctly with RT-real time PCR techniques, cell proliferation essay, ELISA and by counting percentage of beating embryoid bodies (EBs) during ESCs differentiation. The data showed that the paracrine ability of CFs changed dramatically during development, in which interleukin 6 (IL6) increased with maturation. ConM-NCF 1:50 and ConM-NCF 1:5 had opposite effects on the pluripotent markers, although they both reduced mouse ESC proliferation. ConM-ACF 1:50 promoted ESCs pluripotent markers and proliferation, while ConM-ACF 1:5 exerted negative effects. All CF-derived conditioned mediums inhibited cardiac differentiation, but with distinguishable features: ConM-NCF 1:50 slightly decreased the early cardiac differentiation without altering the maturation tendency or cardiac specific markers in EBs at differentiation of day 17; ConM-ACF 1:50 had more significant inhibitory effects on early cardiac differentiation than ConM-NCF 1:50 and impeded cardiac maturation with upregulation of cardiac specific markers. In addition, IL6 neutralization antibody attenuated positive effect of ConM-ACF 1:50 on ESCs proliferation, but had no effects on ConM-NCF 1:50. Long-term IL6 neutralization reduced the percentage of beating EBs at early developmental stage, but did not alter the late cardiac differentiation. Taken together, both the quality and quantity of factors and cytokines secreted by CFs are critical for the ESC fate. IL6 could be a favorable cytokine for ESC pluripotency and the early cardiac differentiation.
Animals ; Embryonic Stem Cells ; Fibroblasts ; Heart ; Mice ; Mouse Embryonic Stem Cells ; Paracrine Communication

Objective: To study the effect of Baoyuan Jiedu decoction on serum interleukin-6 (IL-6) content, expression of muscle atrophy F-box 1(Atrogin-1), muscle ring finger-1 (MuRF-1), uncoupling proteins-2 (UCP-2), uncoupling proteins-3 (UCP-3) in Apc^min/+ mice, in order to explore the mechanism in improving muscle atrophy in cancer cachexia model. Method: The 14-week-old Apc^min/+ cachexia mice model was randomly divided into model group, Baoyuan Jiedu decoction group (23 g·kg^-1) and megestrol group (0.024 g·kg^-1). C57BL/6J mice were normal group, with 10 mice in each group, and given continuous intragastric administration for 12 weeks. The quality of gastrocnemius muscle and the transverse diameter of muscle fibers were measured. The content of IL-6 in serum of Apc^min/+ cachexia mice was detected by enzyme-linked immunosorbent assay (ELISA). The expressions of Atrogin-1, MuRF-1, UCP-2, UCP-3 mRNA and protein in gastrocnemius muscle were detected by Western blot and quantitative real-time fluorescence polymerase chain reaction (Real-time PCR). Result: Compared with the normal group, the weight of gastrocnemius muscle and the transverse diameter of fibers in the model group decreased significantly (P<0.05), while the concentration of IL-6 in serum and the expressions of Atrogin-1, MuRF-1, UCP-2 and UCP-3 in gastrocnemius muscle of mice increased significantly (P<0.05). Compared with the model group, the weight of gastrocnemius muscle, the expression of UCP-3 and protein in the treated group increased significantly (P<0.05). The transverse diameter of muscle fibers increased significantly, whereas the concentration of IL-6 in serum and the expressions of Atrogin-1, MuRF-1, UCP-2 and UCP-3 in gastrocnemius muscle of mice decreased significantly (P<0.05). Conclusion: Reduction of the concentration of IL-6 in serum and the down-regulation of the expressions of Atrogin-1, MuRF-1, UCP-2 and UCP-3 genes may be the possible mechanism of Baoyuan Jiedu decoction in alleviating muscle atrophy in Apc^min/+ cachexia mice model.

Objective To analyse MMACHC mutations for 45 pedigrees with combined methylmalonic aciduria and homocyctinuria by Sanger sequencing, and to discuss the utility of prenatal genetic diagnosis for these pedigrees.Method Peripheral blood was collected from 45 probands and their parents from 2012-2015 in Genetic Counselling Clinic of the First Affiliated Hospital of Zhengzhou University, and the DNA were extracted from the blood.Then the coding sequence of MMACHC gene was amplified by PCR, and the PCR products were further sequenced to detect mutations for each pedigree.For 12 families, chorionic villus sampling was performed on the pregnant women to make prenatal genetic diagnosis.Result There were 14 distinct mutations detected in the 45 pedigrees, and the most frequent mutations are c.609G>A(W203X),c.658-660delAAG(K220del)and c.80A>G (Q27A).Two of those mutations have not been reported before:one is a splicing site mutation c.81+1G>A;while the other is a missense mutation c.665A>G,p.Y222C.Most mutations were found in exon 4.Among the 12 pedigrees who received prenatal diagnosis, 2 fetuses were normal, 7 fetuses were carriers of heterozygous mutation, and the other 3 fetuses were patients with compound heterozygous mutation or homozygous mutation.The couples whose fetuses were normal or carriers continued the gestation, while the couples whose fetuses were patients decided to terminate the pregnancy.After delivery, the outcome of the fetuses was the same as the prenatal diagnose results.Conclusion Two novel mutations of MMACHC were identified and prenatal genetic diagnosis helps to avoid the delivery of combined methylmalonic aciduria and homocyctinuria patients.