Objective: To anlysis the efficacy and safety of cut-umbilical cord milking (C-UCM) compared with immediate cord clamping in preventing anemia and iron deficiency among term cesarean-delivered newborns. Methods: A total of 485 pregnant women planning to deliver by cesarean section were recruited in this randomized controlled trial in Hunan Maternal and Child Health Hospital and Liuyang Maternal and Child Health Care Hospital from July 2016 to April 2019. A block randomization was conducted to evenly allocate them to the controlled group and the C-UCM group. In the controlled group, the cord was clamped within 30 seconds as routine. In the C-UCM group, the cord was first clamped at 25 cm from the newborn\'s navel, and then the blood in the cord was gently squeezed into the newborn\'s body until the cord became white and shriveled. The cord was clamped twice at 2-3 cm from the newborn\'s navel subsequently. Neonatal jaundice, hyperbilirubinemia and polycythemia were monitored before discharge. After the newborns discharged, their hemoglobin, red blood cell count, hematocrit (at the age of 1, 6 and 12 months) and serum ferritin (at the age of 6 and 12 months) were followed up; body length and weight were measured; and information about their feeding and iron supplementation were collected (at the age of 1, 6, 12 and 18 months). The two groups were compared by t test, Mann-Whitney U test, χ² test, or Fisher exact probability method. The hospital was set as a random item, and the mixed effects regression model was used to evaluate the effect of C-UCM on relevant indicators of cesarean-delivered newborns. Results: There were 244 women in the C-UCM group with an average age of (31.9±4.4) years, and 241 in the control group with an average age of (31.8±4.2) years (P>0.05). There was no statistically significant difference between the C-UCM group and the control group at 1, 6 and 12 months of age in hemoglobin [(123.6±14.5) vs (122.2±14.5) g/L, (115.3±9.4) vs (114.1±8.5) g/L, (115.6±9.6) vs (116.1±12.6) g/L] or anemia incidence rate [15.2% (17/112) vs 18.4% (19/103), 22.7% (34/150) vs 26.8% (44/164), 22.3% (25/112) vs 19.5% (22/113)] (all P>0.05). There was no statistically significant difference between the two groups at 6 and 12 months of age in serum ferritin [M (Q1, Q3), 39.9 (24.9, 61.8) vs 43.6 (25.2, 100.9) μg/L, 40.3 (25.4, 259.2) vs 40.3 (26.4, 167.6) μg/L)] or iron deficiency incidence rate [6.1% (5/82) vs 4.2% (3/72), 6.7% (5/75) vs 3.8% (3/80)] (all P>0.05). There were also no significant difference between the two groups in other indicators, such as the Z-score of weight-for-length, the incidence of neonatal jaundice, and the incidence of neonatal hyperbilirubinemia (all P>0.05). After adjusting for the relevant covariates, there were still no significant effects of C-UCM on these outcomes above. Conclusions: Compared to immediate cord clamping, the intervention of gently squeezing 25 cm of the cord does not significantly reduce the risk of anemia or iron deficiency in term cesarean-delivered newborns, nor does it have a significant impact on infant growth and development. Yet this intervention does not increase the risk of jaundice or hyperbilirubinemia in newborns as well.
目的： 分析断脐后捋挤脐血（C-UCM）预防足月剖宫产儿贫血和铁缺乏的有效性和安全性。 方法： 本随机对照试验纳入2016年7月至2019年4月湖南省妇幼保健院和浏阳市妇幼保健院剖宫产孕妇485名，采用区组随机分组将其等比例分配至对照组和C-UCM组。对照组按照临床常规在30 s内完成结扎断脐，C-UCM组在距新生儿肚脐25 cm处行初次结扎断脐，而后轻柔捋挤该段脐带中的血液至新生儿体内、待脐带发白变瘪后再在距肚脐2~3 cm处行二次结扎断脐。新生儿出院前监测黄疸、高胆红素血症和红细胞增多症情况；出院后随访并检测血红蛋白、红细胞计数和红细胞压积（1、6和12月龄）和血清铁蛋白（6和12月龄），测量身长、体重，询问喂养和补铁情况（1、6、12和18月龄），并比较上述指标在两组间差异。将医院设为随机项，采用混合效应回归模型评价C-UCM对剖宫产儿相关指标的影响。 结果： 485名孕妇年龄为（31.8±4.3）岁；对照组241名，年龄为（31.8±4.2）岁，C-UCM组244名，年龄为（31.9±4.4）岁，两组年龄差异无统计学意义（P>0.05）。C-UCM组和对照组新生儿1、6和12月龄血红蛋白水平［（123.6±14.5）比（122.2±14.5）g/L、（115.3±9.4）比（114.1±8.5）g/L、（115.6±9.6）比（116.1±12.6）g/L］和贫血发生率［15.2%（17/112）比18.4%（19/103）、22.7%（34/150）比26.8%（44/164）、22.3%（25/112）比19.5%（22/113）］差异无统计学意义（均P>0.05）。C-UCM组和对照组6和12月龄血清铁蛋白水平［M（Q1，Q3）］［39.9（24.9，61.8）比43.6（25.2，100.9）μg/L，40.3（25.4，259.2）比40.3（26.4，167.6）μg/L］和铁缺乏发生率［6.1%（5/82）比4.2%（3/72）、6.7%（5/75）比3.8%（3/80）］差异均无统计学意义（均P>0.05）。两组间身长别体重Z评分、新生儿黄疸和新生儿高胆红素血症发生率等差异均无统计学意义（均P>0.05）。调整相关协变量后仍未见C-UCM对上述结局有影响（均P>0.05）。 结论： 与立即钳夹脐带相比，未见断脐后轻柔捋挤25 cm脐带血的干预方法降低足月剖宫产儿贫血和铁缺乏的发生风险，未见影响婴儿生长发育，但也未见其增加新生儿黄疸和高胆红素血症发生风险。.

Deferred umbilical cord clamping (DCC) has been employed with wide variation in the United States over the last few decades. This practice has the potential to improve infant health and outcomes at the population health level. Education campaigns and policy interventions can promote DCC use in a safe manner.

BACKGROUND: Intrauterine herpes simplex virus (HSV) infection is uncommon and challenging to diagnose, requiring detection of HSV in skin lesions within 48 h post-birth.
METHODS: A preterm female infant presented with the typical triad of blisters, microcephaly, and chorioretinitis, but the initial diagnostic approach was elusive due to negative results for TORCH pathogens from vesicles/serum. Referred at 7 months for developmental delay and epilepsy, her brain imaging showed calcification and cortical dysplasia. Polymerase chain reaction (PCR) of her preserved dried umbilical cord detected HSV-2 DNA, diagnosing intrauterine HSV infection. HSV-2 was later found in relapsed blisters at 8 months but not in cerebrospinal fluid or brain tissue. A literature review identified 104 congenital/intrauterine HSV cases; 28.8% presented the typical triad, and 50% were diagnosed using specimens collected 48 h post-birth.
CONCLUSIONS: This case marks the first retrospective diagnosis of intrauterine HSV infection via PCR on preserved umbilical cord, underscoring its diagnostic value.

BACKGROUND: Knee osteoarthritis (KOA) presents a prevalent orthopedic condition causing substantial impairment in the quality of life and imposing a significant societal and economic burden. Mesenchymal stromal/stem cells (MSCs), known for their regenerative properties and immunomodulatory effects, have emerged as a promising therapeutic avenue in regenerative medicine. Despite MSCs\' therapeutic potential, their precise mechanisms of action in KOA remain underexplored.
METHODS: Conducted as a randomized, open-label clinical trial, 20 patients will be enrolled, with 10 in the intervention group and 10 in the control group. The primary focus will be to explore the molecular mechanisms associated with MSC therapy. Biomarkers and gene expressions related to cartilage metabolism, inflammation, immune modulation, and pain in the synovial fluid, blood, and tissue samples will be analyzed. Patients will undergo pre- and post-treatment evaluations using patient-reported outcome measures (PROMs) and comprehensive clinical assessments.
CONCLUSIONS: This is an exploratory study with the goal to provide comprehensive insights into the therapeutic effects of MSCs on a molecular level, potentially paving the way for optimized and more effective MSC-based therapies in the management of KOA, as well as furthering the development of novel treatment strategies.
BACKGROUND: ClinicalTrials.gov, NCT06078059. Registered on 5 October 2023.

A 5-year-old neutered female Korean domestic shorthair cat diagnosed with oral squamous cell carcinoma (SCC) presented to the hospital with severe oral purulent discharge, anorexia, and lethargy. Owing to extensive lesions, surgical excision and radiation therapy were not feasible. Instead, prior to metronomic therapy with toceranib, the patient received an intravenous injection of feline umbilical cord-derived mesenchymal stem cells (fUC-MSCs) (1 × 106 cells/10 mL of saline) to reduce inflammation. No acute side effects (such as fever, increased respiratory rate, diarrhea, and vomiting) were observed following stem cell therapy. For 6 days, purulent discharge, bleeding, swelling, a bad odor, and crust exfoliation in the tumor area on the face were dramatically reduced. However, the patient exhibited difficulty in voluntarily receiving foods, and weight loss persisted. Starting from the 7th day, purulent discharge, bleeding, and odor at the SCC area worsened again. Toceranib, low-dose NSAIDs (meloxicam, every other day), antibiotics (cefazoline), and gabapentin were administered; however, they were not effective in reducing the pus, bleeding, foul odor, and crust exfoliation at the SCC area. Symptoms of pain, weakness, and weight loss progressed, leading to the choice of euthanasia with the owner\'s consent approximately 1 month later. This case report reveals that allogeneic fUC-MSCs have a slight short-term effect on purulent discharge, bleeding, odor, and crust exfoliation and may be additional therapy for feline oral SCC.

UNASSIGNED: Malnourished pregnant women are at increased risk of micronutrient deficiency. We assessed the vitamin B12 status in both malnourished and normally nourished pregnant women and their neonates. Additionally, we studied the association between maternal B12 levels, cord B12 levels and neonatal anthropometry.
UNASSIGNED: This cross-sectional study enrolled 63 malnourished and 63 normally nourished mothers and neonates. Maternal and cord blood samples were collected at the time of delivery for estimation of vitamin B12 levels. Maternal and cord vitamin B12 levels were compared using the Mann-Whitney U test. Neonatal anthropometry was correlated with maternal and cord B12 levels using Spearman\'s correlation. Data were analyzed using SPSS version 25.
UNASSIGNED: Mean maternal age was 26.58 yrs. The median cord B12 levels were lower than the maternal B12 levels. Maternal B12 levels showed a strong positive correlation with cord B12 levels (rho = 0.879; p < 0.001). Maternal (p < 0.001) and cord (p < 0.001) vitamin B12 levels were significantly lower in the malnourished group than in the normally nourished group. In malnourished group, 66.8% mothers and 95.2% neonates were Vitamin B12 deficient, whereas 1.5% mothers and 4.7% neonates were vitamin B12 deficient in normally nourished group. In the malnourished group, maternal B12 levels were positively correlated with birth weight (rho 0.363, p = 0.003) and length (rho 0.330, p =0.008), whereas cord B12 levels were positively correlated with birth weight in the normally nourished group. (rho 0.277 p= 0.028).
UNASSIGNED: High rates of vitamin B12 deficiency were observed in malnourished mothers and neonates. There was a positive correlation between birth weight, length, and maternal vitamin B12 levels in malnourished mothers. These findings emphasize the need to address maternal malnutrition and vitamin B12 deficiency to improve neonatal health.

UNASSIGNED: Congenital uterine anomalies during pregnancy increase the risk of pregnancy complications such as miscarriage, preterm delivery, fetal malpresentation, cesarean delivery, and fetal growth restriction. However, few studies have examined uterine anomalies in relation to perinatal complications other than those mentioned above. We investigated the association between pregnancies complicated by congenital uterine anomalies and various perinatal outcomes at our institution.
UNASSIGNED: This retrospective cohort study was conducted from January 2009 to May 2021. We included cases of uterine anomalies, such as septate, bicornuate, unicornuate, and didelphic uterus. First, the perinatal complications and neonatal outcomes were compared between pregnancies complicated by uterine anomalies and those with normal uteri. Second, we conducted an analysis based on the type of uterine anomalies classified into two groups: the minor anomaly group consisted of anomalies limited to the uterine cavity, such as the septate uterus, whereas the major anomaly group included anomalies affecting the uterine shape, such as bicornuate, unicornuate, and didelphic uterus. We compared the incidence of perinatal complications among the major anomaly, minor anomaly, and normal uterus groups.
UNASSIGNED: During the study period, 45 pregnancies were complicated with uterine anomalies. The minor anomaly group included 11 patients and the major anomaly group included 34 patients. The incidence of fetal malpresentation was significantly higher in the uterine anomaly group than in the normal uterus group (18% vs. 3.7%, p = .04). Furthermore, the frequency of abnormal placental cord insertion was significantly higher in the uterine anomaly group (16% vs. 3.7%, p = .01). Examination based on the type of uterine anomaly revealed significant differences in cervical incompetence, malpresentation, cesarean section, and abnormal placental cord insertion. Cervical incompetence was more likely in patients with minor anomalies. In contrast, fetal malpresentation, cesarean section, and abnormal placental cord insertion were more likely in the major anomaly group.
UNASSIGNED: In addition to the findings reported in previous studies, abnormal placental cord insertion was more frequent in pregnancies complicated by uterine anomalies.

BACKGROUND: The leading cause of end-stage renal disease (ESRD) is diabetic nephropathy (DN). Podocyte damage is an early event in the development of DN. Currently, there is no effective treatment strategy that can slow the progression of DN or reverse its onset. The role of mesenchymal stem cells (MSCs) transplantation in diabetes and its complications has been extensively studied, and diabetic nephropathy has been a major focus. Irbesartan exerts reno-protective effects independent of lowering blood pressure, can reduce the incidence of proteinuria in rats, and is widely used clinically. However, it remains undetermined whether the combined utilization of the angiotensin II receptor antagonist irbesartan and MSCs could enhance efficacy in addressing DN.
METHODS: A commonly used method for modeling type 2 diabetic nephropathy (T2DN) was established using a high-fat diet and a single low-dose injection of STZ (35 mg/kg). The animals were divided into the following 5 groups: (1) the control group (CON), (2) the diabetic nephropathy group (DN), (3) the mesenchymal stem cells treatment group (MSCs), (4) the irbesartan treatment group (Irb), and (5) the combined administration group (MSC + Irb). MSCs (2 × 106 cells/rat) were injected every 10 days through the tail vein for a total of three injections; irbesartan (30 mg/kg/d) was administered by gavage. Additionally, the safety and homing of mesenchymal stem cells were verified using positron emission tomography (PET) imaging.
RESULTS: The combination treatment significantly reduced the UACR, kidney index, IGPTT, HOMA-IR, BUN, serum creatine, and related inflammatory factor levels and significantly improved renal function parameters and the expression of proteins related to glomerular podocyte injury in rats. Moreover, MSCs can homing target to damaged kidneys.
CONCLUSIONS: Compared to the administration of MSCs or irbesartan alone, the combination of MSCs and irbesartan exerted better protective effects on glomerular podocyte injury, providing new ideas for the clinical application of mesenchymal stem cells.

Intervertebral disc degeneration (IVDD) is a prevalent chronic condition causing spinal pain and functional impairment. This study investigates the role of extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUCMSCs) in regulating IVDD. Using RNA-seq, we analyzed differential expressions of lncRNA and miRNA in nucleus pulposus tissues from various mouse groups. We identified key regulatory molecules, MALAT1 and miRNA-138-5p, which contribute to IVDD. Further experiments demonstrated that MALAT1 can up-regulate SLC7A11 expression by competitively binding to miR-138-5p, forming a MALAT1/miR-138-5p/SLC7A11 coexpression regulatory network. This study elucidates the molecular mechanism by which hUCMSC-derived EVs regulate IVDD and could help develop novel therapeutic strategies for treating this condition. Our findings demonstrate that hUCMSCs-EVs inhibit ferroptosis in nucleus pulposus cells, thereby improving IVDD. These results highlight the therapeutic potential of hUCMSCs-EVs in ameliorating the development of IVDD, offering significant scientific and clinical implications for new treatments.

BACKGROUND: Human mesenchymal stem cells originating from umbilical cord matrix are a promising therapeutic resource, and their differentiated cells are spotlighted as a tissue regeneration treatment. However, there are limitations to the medical use of differentiated cells from human umbilical cord matrix-mesenchymal stem cells (hUCM-MSCs), such as efficient differentiation methods.
METHODS: To effectively differentiate hUCM-MSCs into hepatocyte-like cells (HLCs), we used the ROCK inhibitor, fasudil, which is known to induce endoderm formation, and gelatin, which provides extracellular matrix to the differentiated cells. To estimate a differentiation efficiency of early stage according to combination of gelatin and fasudil, transcription analysis was conducted. Moreover, to demonstrate that organelle states affect differentiation, we performed transcription, tomographic, and mitochondrial function analysis at each stage of hepatic differentiation. Finally, we evaluated hepatocyte function based on the expression of mRNA and protein, secretion of albumin, and activity of CYP3A4 in mature HLCs.
RESULTS: Fasudil induced endoderm-related genes (GATA4, SOX17, and FOXA2) in hUCM-MSCs, and it also induced lipid droplets (LDs) inside the differentiated cells. However, the excessive induction of LDs caused by fasudil inhibited mitochondrial function and prevented differentiation into hepatoblasts. To prevent the excessive LDs formation, we used gelatin as a coating material. When hUCM-MSCs were induced into hepatoblasts with fasudil on high-viscosity (1%) gelatin-coated dishes, hepatoblast-related genes (AFP and HNF4A) showed significant upregulation on high-viscosity gelatin-coated dishes compared to those treated with low-viscosity (0.1%) gelatin. Moreover, other germline cell fates, such as ectoderm and mesoderm, were repressed under these conditions. In addition, LDs abundance was also reduced, whereas mitochondrial function was increased. On the other hand, unlike early stage of the differentiation, low viscosity gelatin was more effective in generating mature HLCs. In this condition, the accumulation of LDs was inhibited in the cells, and mitochondria were activated. Consequently, HLCs originated from hUCM-MSCs were genetically and functionally more matured in low-viscosity gelatin.
CONCLUSIONS: This study demonstrated an effective method for differentiating hUCM-MSCs into hepatic cells using fasudil and gelatin of varying viscosities. Moreover, we suggest that efficient hepatic differentiation and the function of hepatic cells differentiated from hUCM-MSCs depend not only on genetic changes but also on the regulation of organelle states.