Effects of timing of cord clamping on neonatal hemoglobin and bilirubin levels in preterm and term infants-A prospective observational cohort study.

BACKGROUND: Delayed cord clamping (DCC) is a proven beneficial intervention, but the suggested timings of DCC vary from 30 to 300 seconds after birth or until cord pulsation stops. This study aimed to find the optimum timing of DCC to maximize the benefits such as an increase in hemoglobin, and hematocrit without increasing the risks of polycythemia and hyperbilirubinemia. METHODS: We conducted a single-center prospective observational cohort study. All singleton neonates with gestational age ≥ 28 weeks born at the center in the 17 months of the study period from November 2020 to March 2022 were enrolled. Participants were divided into four groups based on DCC time: group A: <60 sec, group B: 60-119 sec, group C: 120-180 sec, and group D: >180 sec. The primary outcome was the levels of hemoglobin, hematocrit, and bilirubin at 48 hours of life. RESULTS: Four hundred and eight neonates were enrolled. They were divided into four groups based on the timing of DCC (group A: n = 52, group B: n = 137, group C: n = 155, group D: n = 64). With an increase in the duration of DCC, there was an increase in the level of hemoglobin and hematocrit without an increase in the risk of polycythemia or neonatal hyperbilirubinemia. The benefits were best in group C (120-180 sec) and group D (>180 sec). CONCLUSIONS: DCC of ≥ 120 seconds appears to be optimal where hemoglobin and hematocrit are highest without an increase in the risk of neonatal hyperbilirubinemia. The risk of adverse effects like polycythemia or neonatal hyperbilirubinemia requiring phototherapy did not increase even after extending the time of cord clamping to >180 seconds.

RTA-408 Regulates p-NF-κB/TSLP/STAT5 Signaling to Ameliorate Nociceptive Hypersensitivity in Chronic Constriction Injury Rats.

Neuropathic pain following nerve injury is a complex condition, which often puts a negative impact on life and remains a sustained problem. To make pain management better is of great significance and unmet need. RTA 408 (Omaveloxone) is a traditional Asian medicine with a valid anti-inflammatory property. Thus, we aim to investigate the therapeutic effect of RTA-408 on mechanical allodynia in chronic constriction injury (CCI) rats as well as the underlying mechanisms. Neuropathic pain was induced by using CCI of the rats' sciatic nerve (SN) and the behavior testing was measured by calibrated forceps testing. Activation of Nrf-2, the phosphorylation of nuclear factor-κB (NF-κB), and the inflammatory response were assessed by western blots. The number of apoptotic neurons and degree of glial cell reaction were examined by immunofluorescence assay. RTA-408 exerts an analgesic effect on CCI rats. RTA-408 reduces neuronal apoptosis and glial cell activation by increasing Nrf-2 expression and decreasing the inflammatory response (TNF-α/ p-NF-κB/ TSLP/ STAT5). These data suggest that RTA-408 is a candidate with potential to reduce nociceptive hypersensitivity after CCI by targeting TSLP/STAT5 signaling.

Delayed cord clamping versus cord milking in vigorous neonates ≥35 weeks gestation born via cesarean: A Randomized clinical trial.

BACKGROUND: Delayed cord clamping (DCC) is the recommended strategy in neonates not requiring resuscitation, but umbilical cord milking (UCM) can also be used in term babies. DCC has been found to offer advantages more than just placental transfusion. OBJECTIVE: To compare the neonatal outcomes of DCC and UCM at birth in vigorous neonates ≥35 weeks born via cesarean section. METHODS: We included all vigorous neonates born ≥35 weeks of gestation through the cesarean section in this open-label randomized controlled trial. They were randomized into Group-A (DCC-cord was clamped 60 s after birth) or Group B(UCM). For neonates in Group B, the intact cord was milked at 25 cm from the stump 3 times towards the neonate and then clamped. The primary outcome was hematocrit at 72 h of life. Secondary outcomes were serum ferritin between 6 and 10 weeks of life, serum bilirubin at 72 h of life, need and duration of phototherapy, respiratory distress, hypoglycemia, hypotension, and sepsis. RESULTS: Baseline characteristics were similar in both the groups. The mean hematocrit at 72 h was more in the DCC group compared to the UCM group [(55.60±4.50) vs (53.89±4.44), MD (95% CI) = 1.71 (0.26, 3.16); p = 0.021]. There was no significant difference in median serum ferritin between the groups [102.88(84.67-173.24) vs 137.93(85.15-230.40); p = 0.173]. There was no significant difference in clinical outcomes. CONCLUSION: In neonates born via cesarean section, DCC resulted in improved hematocrit levels by 72 hours compared to UCM. DCC results in better placental transfusion.

Efficacy of Fu's Subcutaneous Needling on Sciatic Nerve Pain: Behavioral and Electrophysiological Changes in a Chronic Constriction Injury Rat Model.

Fu's subcutaneous needling (FSN), an invented acupuncture technique from traditional Chinese medicine, is used worldwide for pain relief. However, the mechanisms of action are still not fully understood. During FSN treatment, the FSN needle is inserted and retained in the subcutaneous tissues for a long duration with a swaying movement. However, challenges arise from maintaining a posture while manipulating FSN in animal models (e.g., rats) for researchers. Uncomfortable treatment can lead to fear and resistance to FSN needles, increasing the risk of injury and may even affect research data. Anesthesia may also affect the study results too. Hence, there is a need for strategies in FSN therapy on animals that minimize injury during the intervention. This study employs a chronic constriction injury model in Sprague-Dawley rats to induce neuropathic pain. This model replicates the pain induced by nerve injury observed in humans through surgical constriction of a peripheral nerve, mimicking the compression or entrapment seen in conditions such as nerve compression syndromes and peripheral neuropathies. We introduce an appropriate manipulation for easily inserting an FSN needle into the subcutaneous layer of the animal's body, including needle insertion and direction, needle retention, and swaying movement. Minimizing the rat's discomfort prevents the rat from being tense, which causes the muscle to contract and hinder the entry of the needle and improves the study efficiency.

Effects of delayed cord clamping at different time intervals in late preterm and term neonates: a randomized controlled trial.

Delayed cord clamping (DCC) at delivery has well-recognized benefits; however, current scientific guidelines lack uniformity in its definition. This parallel-group, three-arm assessor-blinded randomized controlled trial compared the effects of three different timings of DCC at 30, 60, and 120 s on venous hematocrit and serum ferritin levels in late preterm and term neonates not requiring resuscitation. Eligible newborns (n = 204) were randomized to DCC 30 (n = 65), DCC 60 (n = 70), and DCC 120 (n = 69) groups immediately after delivery. The primary outcome variable was venous hematocrit at 24 ± 2 h. Secondary outcome variables were respiratory support, axillary temperature, vital parameters, incidences of polycythemia, neonatal hyperbilirubinemia (NNH), need and duration of phototherapy, and postpartum hemorrhage (PPH). Additionally, serum ferritin levels, the incidence of iron deficiency, exclusive breastfeeding (EBF) rate, and anthropometric parameters were assessed during post-discharge follow-up at 12 ± 2 weeks. Over one-third of the included mothers were anemic. DCC 120 was associated with a significant increase in the mean hematocrit by 2%, incidence of polycythemia, and duration of phototherapy, compared to DCC30 and DCC60; though the incidence of NNH and need for phototherapy was similar. No other serious neonatal or maternal adverse events including PPH were observed. No significant difference was documented in serum ferritin, incidences of iron deficiency, and growth parameters at 3 months even in the presence of a high EBF rate.   Conclusion: The standard recommendation of DCC at 30-60 s may be considered a safe and effective intervention in the busy settings of low-middle-income countries with a high prevalence of maternal anemia.   Trial registration: Clinical trial registry of India (CTRI/2021/10/037070). What is Known: • The benefits of delayed cord clamping (DCC) makes it an increasingly well-accepted practice in the delivery room. • However, uncertainty continues regarding the optimal timing of clamping; this may be of concern both in the neonate and the mother. What is New: • DCC at 120 s led to higher hematocrit, polycythemia and longer duration of phototherapy, without any difference in serum ferritin, and incidence of iron deficiency. • DCC at 30-60 s may be considered a safe and effective intervention in LMICs.

Spinal Sirtuin 3 Contributes to Electroacupuncture Analgesia in Mice With Chronic Constriction Injury-Induced Neuropathic Pain.

BACKGROUND: Electroacupuncture (EA) is a traditional Chinese therapeutic technique that has a beneficial effect on neuropathic pain; however, the specific mechanism remains unclear. In this study, we investigated whether EA inhibits spinal Ca/calmodulin-dependent protein kinase II (CaMKIIα) phosphorylation through Sirtuin 3 (SIRT3) protein, thus relieving neuropathic pain. MATERIALS AND METHODS: We used wild-type and SIRT3 knockout (SIRT3-/-) mice and used chronic constriction injury (CCI) as a pain model. We performed Western blotting, immunostaining, von Frey, and Hargreaves tests to gather biochemical and behavioral data. Downregulation and overexpression and spinal SIRT3 protein were achieved by intraspinal injection of SIRT3 small interfering RNA and intraspinal injection of lentivirus-SIRT3. To test the hypothesis that CaMKIIα signaling was involved in the analgesic effects of EA, we expressed CaMKIIα-specific designer receptors exclusively activated by designer drugs (DREADDs) in the spinal dorsal horn (SDH) of mice. RESULTS: These results showed that the mechanical and thermal hyperalgesia induced by CCI was related to the decreased spinal SIRT3 expression in the SDH of mice. A significant reduction of mechanical and thermal thresholds was found in the SIRT3-/- mice. SIRT3 overexpression or EA treatment alleviated CCI-induced neuropathic pain and prevented the spinal CaMKIIα phosphorylation. Most importantly, EA increased the expression of spinal SIRT3 protein in the SDH. Downregulation of spinal SIRT3 or CaMKIIα Gq-DREADD activation inhibited the regulatory effect of EA on neuropathic pain. CONCLUSION: Our results showed that CaMKIIα phosphorylation was inhibited by spinal SIRT3 in neuropathic pain and that EA attenuated CCI-induced neuropathic pain mainly by upregulating spinal SIRT3 expression in the SDH of mice.

Umbilical cord milking in nonvigorous infants: a cluster-randomized crossover trial.

BACKGROUND: Delayed cord clamping and umbilical cord milking provide placental transfusion to vigorous newborns. Delayed cord clamping in nonvigorous newborns may not be provided owing to a perceived need for immediate resuscitation. Umbilical cord milking is an alternative, as it can be performed more quickly than delayed cord clamping and may confer similar benefits. OBJECTIVE: We hypothesized that umbilical cord milking would reduce admission to the neonatal intensive care unit compared with early cord clamping in nonvigorous newborns born between 35 and 42 weeks' gestation. STUDY DESIGN: This was a pragmatic cluster-randomized crossover trial of infants born at 35 to 42 weeks' gestation in 10 medical centers in 3 countries between January 2019 and May 2021. The centers were randomized to umbilical cord milking or early cord clamping for approximately 1 year and then crossed over for an additional year or until the required number of consented subjects was reached. Waiver of consent as obtained in all centers to implement the intervention. Infants were eligible if nonvigorous at birth (poor tone, pale color, or lack of breathing in the first 15 seconds after birth) and were assigned to umbilical cord milking or early cord clamping according to their birth hospital randomization assignment. The baseline characteristics and outcomes were collected following deferred informed consent. The primary outcome was admission to the neonatal intensive care unit for predefined criteria. The main safety outcome was hypoxic-ischemic encephalopathy. Data were analyzed by the intention-to-treat concept. RESULTS: Among 16,234 screened newborns, 1780 were eligible (905 umbilical cord milking, 875 early cord clamping), and 1730 had primary outcome data for analysis (97% of eligible; 872 umbilical cord milking, 858 early cord clamping) either via informed consent (606 umbilical cord milking, 601 early cord clamping) or waiver of informed consent (266 umbilical cord milking, 257 early cord clamping). The difference in the frequency of neonatal intensive care unit admission using predefined criteria between the umbilical cord milking (23%) and early cord clamping (28%) groups did not reach statistical significance (modeled odds ratio, 0.69; 95% confidence interval, 0.41-1.14). Umbilical cord milking was associated with predefined secondary outcomes, including higher hemoglobin (modeled mean difference between umbilical cord milking and early cord clamping groups 0.68 g/dL, 95% confidence interval, 0.31-1.05), lower odds of abnormal 1-minute Apgar scores (Apgar ≤3, 30% vs 34%, crude odds ratio, 0.72; 95% confidence interval, 0.56-0.92); cardiorespiratory support at delivery (61% vs 71%, modeled odds ratio, 0.57; 95% confidence interval, 0.33-0.99), and therapeutic hypothermia (3% vs 4%, crude odds ratio, 0.57; 95% confidence interval, 0.33-0.99). Moderate-to-severe hypoxic-ischemic encephalopathy was significantly less common with umbilical cord milking (1% vs 3%, crude odds ratio, 0.48; 95% confidence interval, 0.24-0.96). No significant differences were observed for normal saline bolus, phototherapy, abnormal 5-minute Apgar scores (Apgar ≤6, 15.7% vs 18.8%, crude odds ratio, 0.81; 95% confidence interval, 0.62-1.06), or a serious adverse event composite of death before discharge. CONCLUSION: Among nonvigorous infants born at 35 to 42 weeks' gestation, umbilical cord milking did not reduce neonatal intensive care unit admission for predefined criteria. However, infants in the umbilical cord milking arm had higher hemoglobin, received less delivery room cardiorespiratory support, had a lower incidence of moderate-to-severe hypoxic-ischemic encephalopathy, and received less therapeutic hypothermia. These data may provide the first randomized controlled trial evidence that umbilical cord milking in nonvigorous infants is feasible, safe and, superior to early cord clamping.

Effects of Capparis Spinosa extract on the neuropathic pain induced by chronic constriction injury in rats.

Neuropathic pain, a chronic pain condition, puts a considerable burden on its patients. However, different pathophysiological characteristics of neuropathic pain make the current treatment medications insufficient in controlling pain. Identifying treatment effects with Capparis Spinosa hydro-alcoholic extract in an animal model of neuropathic pain. Liquid chromatography-mass spectrometry (LC-MS) was used to identify the components of C. Spinosa hydro-alcoholic extract. To establish a neuropathic pain model, adult male Wistar rats underwent chronic constriction injury (CCI) surgery in their left sciatic nerve. Male wistar rats were divided into four groups: CCI, Sham, CCI with C. Spinosa (100 mg/kg), and CCI with C. Spinosa (200 mg/kg). Rats were treated with a hydro-alcoholic extract from aerial parts of the C. Spinosa (orally, daily) starting from CCI induction until 14 days after. Behavioral tests (mechanical allodynia, cold allodynia, and thermal hyperalgesia) and biochemical tests (IL-1ß, TNF-α, MDA, and total thiol) were taken from animals. The LC-MS analysis identified 22 compounds in C. Spinosa extract with the predominance of flavonoids. CCI produced a significant (P < 0.001) increase allodynia (mechanical and cold) and thermal hyperalgesia in comparison with sham group. Oral administration of C. Spinosa significantly (P < 0.05) ameliorated CCI-induced nociceptive pain compared with CCI group. Spinal cord specimens of CCI rats had significant (P < 0.05) elevated inflammation status (↑IL-1ß, ↑TNF-α), and significant (P < 0.05) decreased antioxidative status (↑MDA, ↓total thiol) in comparison with the sham group. These changes were reversed following C. Spinosa treatment. C. Spinosa alleviates neuropathic pain by exhibiting antioxidative and anti-inflammatory effects. The responsible components for these effects are possibly the flavonoid compounds in C. Spinosa extract.

Shunxin decoction improves diastolic function in rats with heart failure with preserved ejection fraction induced by abdominal aorta constriction through cyclic guanosine monophosphate-dependent protein kinase Signaling Pathway.

OBJECTIVE: To determine whether Shunxin decoction improves diastolic function in rats with heart failure with preserved ejection fraction (HFpEF) by regulating the cyclic guanosine monophosphate-dependent protein kinase (cGMP-PKG) signaling pathway. METHODS: Except for control group 8 and sham surgery group 8, the remaining 32 male Sprague-Dawlay rats were developed into HFpEF rat models using the abdominal aorta constriction method. These rats in the HFpEF model were randomly divided into the model group, the Shunxin high-dose group, the Shunxin low-dose group, and the Qiliqiangxin capsule group. The three groups received high-dose Shunxin decoction, low-dose Shunxin decoction, and Qiliqiangxin capsule by gavage, respectively, for 14 d. After the intervention, the diastolic function of each rat was evaluated by testing E/A, heart index, hematoxylin-eosin staining, Masson, myocardial ultrastructure, and N-terminal pro-brain natriuretic peptide (NT-proBNP). The Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) software was used to predict targets for which Shunxin decoction acts on the cGMP-PKG pathway. Natriuretic peptide receptor A (NPRA) and guanylate cyclase (GC) were detected by immunohistochemistry, and eNOS, phosphodiesterase 5A (PDE5A), and cGMP-dependent protein kinase 1(PKG I) were determined by Western blotting. RESULTS: Compared to the model group, the thickness of the interventricular septum at the end of diastole (IVSd) and the thickness of the posterior wall at the end of diastole (PWd) of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group were all significantly reduced ( < 0.01). Furthermore, Shunxin decoction high-dose group E/A value was decreased ( < 0.01). Compared to the model group, the expression of NPRA and GC increased in the Shunxin decoction low-dose group and the Qiliqiangxin capsule group ( < 0.01). Compared to the model group, the expressions of eNOS and PKG I increased ( < 0.05) in the Shunxin decoction high-dose group. The expression of PDE5A expression decreased in the myocardium of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group compared to the model group ( < 0.01). CONCLUSIONS: Shunxin decoction can improve diastolic function in rats with HFpEF. It increases the expression of NPRA, GC, and eNOS in the myocardial cell cGMP-PKG signaling pathway, upregulates cGMP expression, decreases PDE5A expression to reduce the cGMP degradation. Thus, the cGMP continually stimulates PKG I, reversing myocardial hypertrophy and improving myocardial compliance in HFpEF rats.

Analgesic effect of nobiletin against neuropathic pain induced by the chronic constriction injury of the sciatic nerve in mice.

Neuropathic pain is chronic pain resulting from central or peripheral nerve damage that remains difficult to treat. Current evidence suggests that nobiletin, isolated from Citrus reticulata Blanco, possesses analgesic and neuroprotective effects. However, its effect on neuropathic pain has not been reported. This study evaluated the analgesic effect of nobiletin on neuropathic pain induced by chronic constriction injury (CCI) in mice. In vivo, mice were intragastrically administered with nobiletin (30, 60, 120 mg/kg) for eight consecutive days, respectively. Our study indicated that nobiletin ameliorated mechanical allodynia, cold allodynia and thermal hyperalgesia on CCI mice at doses that do not induce significant sedation. Moreover, nobiletin could ameliorate axonal and myelin injury of the sciatic nerve and further restore abnormal sciatic nerve electrical activity on CCI mice. In vitro studies indicated that nobiletin could suppress the proteins and mRNA expression of the IRF5/P2X4R/BDNF signalling pathway in fibronectin-induced BV2 cells. Overall, our results indicated that nobiletin might exert an analgesic effect on CCI-induced neuropathic pain in mice by inhibiting the IRF5/P2X4R/BDNF signalling pathway in spinal microglia. This study provided a novel potential therapeutic drug for neuropathic pain and new insights into the pharmacological action of nobiletin.

Co-Combination of Pregabalin and Withaniacoagulans-Extract-Loaded Topical Gel Alleviates Allodynia and Hyperalgesia in the Chronic Sciatic Nerve Constriction Injury for Neuropathic Pain in Animal Model.

The current study reports the fabrication of co-combination gel using Pregabalin and Withania coagulans fruit extract to validate its effectiveness for neuropathic pain in chronic constriction injury (CCI) rat models. Three topical gels were prepared using Carbopol 934 through a pseudo-ternary phase diagram incorporating the Pregabalin (2.5%), Withania coagulans extract (2%), and co-combination of both Pregabalin (2.5%) and Withania coagulans extract (2%). Gels were characterized. FTIR showed a successful polymeric network of the gel without any interaction. The drug distribution at the molecular level was confirmed by XRD. The AFM images topographically indicated the rough surface of gels with a size range from 0.25 to 330 nm. DSC showed the disappearance of sharp peaks of the drug and extract, showing successful incorporation into the polymeric network of gels. The in vitro drug release of co-combination gel was 73% over 48 h. The mechanism of drug release by combination gel was Higuchi+ fickian with values of n (0.282) and R2 (0.947). An in vivo study for pain assessment via four methods: (i) heat hyperalgesia, (ii) cold allodynia, (iii) mechano-hyperalgesia, and (iv) dynamic mechano-allodynia, confirmed that topical treatment with co-combination gel reduced the pain significantly as indicated by the p value: R1 (p < 0.001), R2 (p < 0.001), R3 (p < 0.015), and R4 (p < 0.0344). The significance order was R2 (****) > R1 (***) > R3 (**) > R4 (*) > R5 (ns).

Hyperoxia evokes pericyte-mediated capillary constriction.

Oxygen supplementation is regularly prescribed to patients to treat or prevent hypoxia. However, excess oxygenation can lead to reduced cerebral blood flow (CBF) in healthy subjects and worsen the neurological outcome of critically ill patients. Most studies on the vascular effects of hyperoxia focus on arteries but there is no research on the effects on cerebral capillary pericytes, which are major regulators of CBF. Here, we used bright-field imaging of cerebral capillaries and modeling of CBF to show that hyperoxia (95% superfused O2) led to an increase in intracellular calcium level in pericytes and a significant capillary constriction, sufficient to cause an estimated 25% decrease in CBF. Although hyperoxia is reported to cause vascular smooth muscle cell contraction via generation of reactive oxygen species (ROS), endothelin-1 and 20-HETE, we found that increased cytosolic and mitochondrial ROS levels and endothelin release were not involved in the pericyte-mediated capillary constriction. However, a 20-HETE synthesis blocker greatly reduced the hyperoxia-evoked capillary constriction. Our findings establish pericytes as regulators of CBF in hyperoxia and 20-HETE synthesis as an oxygen sensor in CBF regulation. The results also provide a mechanism by which clinically administered oxygen can lead to a worse neurological outcome.

[Influence of umbilical cord milking versus delayed cord clamping on the early prognosis of preterm infants with a gestational age of <34 weeks: a Meta analysis]. / 脐带挤压与延迟断脐对胎龄<34周早产儿早期预后影响的Meta分析.

OBJECTIVES: To study the influence of umbilical cord milking versus delayed cord clamping on the early prognosis of preterm infants with a gestational age of <34 weeks. METHODS: PubMed, Web of Science, Embase, the Cochrane Library, CINAHL, China National Knowledge Infrastructure, Wanfang Data, Weipu Database, and SinoMed were searched for randomized controlled trials on umbilical cord milking versus delayed cord clamping in preterm infants with a gestational age of <34 weeks published up to November 2021. According to the inclusion and exclusion criteria, two researchers independently performed literature screening, quality evaluation, and data extraction. Review Manger 5.4 was used for Meta analysis. RESULTS: A total of 11 articles were included in the analysis, with 1 621 preterm infants in total, among whom there were 809 infants in the umbilical cord milking group and 812 in the delayed cord clamping group. The Meta analysis showed that compared with delayed cord clamping, umbilical cord milking increased the mean blood pressure after birth (weighted mean difference=3.61, 95%CI: 0.73-6.50, P=0.01), but it also increased the incidence rate of severe intraventricular hemorrhage (RR=1.83, 95%CI: 1.08-3.09, P=0.02). There were no significant differences between the two groups in hemoglobin, hematocrit, blood transfusion rate, proportion of infants undergoing phototherapy, bilirubin peak, and incidence rates of complications such as periventricular leukomalacia and necrotizing enterocolitis (P>0.05). CONCLUSIONS: Compared with delayed cord clamping, umbilical cord milking may increase the risk of severe intraventricular hemorrhage in preterm infants with a gestational age of <34 weeks; however, more high-quality large-sample randomized controlled trials are needed for further confirmation.

Differential effects of delayed cord clamping on bilirubin levels in normal and diabetic pregnancies.

The purpose of the study is to investigate the effects of delayed cord clamping on bilirubin levels and phototherapy rates in neonates of diabetic mothers. This was a prospective study that enrolled pregnant women without pregnancy complications and those with diabetes. Their neonates were randomized in a 1:1 ratio to delayed cord clamping. The main outcomes were the neonatal transcutaneous bilirubin values on 2-4 days postpartum and the rate of requiring phototherapy in infants. A total of 261 pregnant women were included in the final analysis (132 women with diabetic pregnancies and 129 women with normal pregnancies). In diabetic pregnancies, neonatal bilirubin levels on the 2-4 days postpartum and phototherapy rates were significantly higher in the delayed cord clamping group than in the immediate cord clamping group (7.65 ± 1.83 vs 8.25 ± 1.96, P = 0.039; 10.35 ± 2.23 vs 11.54 ± 2.56, P = 0.002; 11.54 ± 2.94 vs 12.83 ± 3.07 P = 0.024, 18.2% vs 6.3%, P = 0.042), while in normal pregnancies, there was no statistical difference in bilirubin values and phototherapy rates between the delayed cord clamping group and the immediate cord clamping group (P > 0.05). After receiving delayed cord clamping, bilirubin levels on the third postnatal day and the rate of requiring phototherapy in infants were higher in the diabetic pregnancy group than in the normal pregnancy group (10.35 ± 2.23 vs 11.54 ± 2.56, P = 0.013). CONCLUSION: Delayed cord clamping increased the risk of jaundice in newborns born to diabetic mothers, but had no effect in newborns from mothers with normal pregnancies. DCC may be a risk factor for increased bilirubin in infants of diabetic mothers. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04369313; date of registration: April 27, 2020 (retrospectively registered). WHAT IS KNOWN: • Delayed cord clamping had significant benefits for newborns by increasing neonatal hemoglobin levels and reducing the risk of neonatal anemia, etc. • Delayed cord clamping may lead to neonatal hyperemia, erythrocytosis, and hyperbilirubinemia, which increases the risk of neonatal jaundice. WHAT IS NEW: • Our trial focused on the differential effects of delayed cord clamping on jaundice in full-term newborns between diabetic pregnancies and normal pregnancies. And newborns of diabetic mothers who received delayed cord clamping had a significantly increased risk of jaundice compared to newborns with normal pregnancy. • Delayed cord clamping may be a risk factor for increased bilirubin levels in neonates of diabetic mothers.

Therapeutic effect of paeoniflorin on chronic constriction injury of the sciatic nerve via the inhibition of Schwann cell apoptosis.

Therapeutic drugs of chronic neuralgia have a high risk of addiction, making it crucial to identify novel drugs for chronic neuralgia. This study aimed to explore the therapeutic effect of paeoniflorin on chronic sciatica via inhibiting Schwann cell apoptosis. 28 SD rats were randomly divided into four groups, including the sham operation group, chronic constriction injury (CCI) group, mecobalamin group, and paeoniflorin group. The therapeutic effect and mechanism of paeoniflorin were evaluated via rat and cell experiments. Mechanical, hot, or cold hyperalgesia was induced in the rats after CCI operation, while paeoniflorin relieved chronic neuralgia. Besides, paeoniflorin decreased the levels of IL1, IL6, TNF-α, CRP, and LPS and increased the level of IL10 in serum. As for the sciatic nerve, the number of inflammatory cells was decreased, and Schwann cells were present after paeoniflorin treatment, and paeoniflorin promoted the recovery of nerve structure. In cell experiments, LPS induced Schwann cell apoptosis via the TLR4/NF-kB pathway. And paeoniflorin attenuated LPS-induced Schwann cell apoptosis by decreasing the levels of TLR4, p-NF-kB, caspase3, cleaved-caspase3, and cleaved-caspase7. Overall, these results suggest that paeoniflorin alleviates chronic sciatica by decreasing inflammatory factor levels and promotes the repair of damaged nerves by reducing Schwann cell apoptosis.

Practices and attitudes about delayed umbilical cord clamping for term infants: a descriptive survey among midwives.

The aim of this study was to assess variations in midwives' practices of cord clamping (early versus delayed) and to identify factors potentially associated with delayed clamping. This was a descriptive cross-sectional survey by self-administered online questionnaire among French midwives working in delivery rooms from March to July 2018. We obtained complete responses from 350 midwives. Only 120 (34.3%) reported always or sometimes performing delayed cord clamping at one minute or more after birth. Delayed cord clamping was significantly associated with midwives' experience (adjusted OR 3.99; 95% confidence interval [CI] 2.10, 7.83 for experience >10 years), maternity unit written protocol (adjusted OR (aOR) 5.17; 95% CI 1.88, 16.00), knowledge of guidelines (aOR 3.33; 95% CI 1.98, 5.71) and neonatal care level 1 (aOR 2.95; 95% CI 1.53, 5.78).Impact StatementWhat is already know on this subject? Despite benefits and the safety of delayed cord clamping, many newborns likely had their umbilical cords clamped immediately after delivery as part of routine care or because providers were not convinced of the benefits of delayed clamping.What do the results of this study add? Most of the midwives surveyed did not systematically delay cord clamping. Individual and organisational factors were associated with adherence to guidelines regarding delayed cord clamping.What are the implications of these findings for clinical and/or further research? A protocol should be implemented in every maternity unit with information about the benefits and risks of delayed cord clamping to reduce variations in practice and improve the safety of care.

Effects of delayed cord clamping on neonatal hyperbilirubinemia in pre-gestational diabetes at term.

OBJECTIVE: To evaluate the effects of delayed cord clamping on neonatal hyperbilirubinemia in infants born to patients diagnosed with pre-gestational diabetes (type I or type II). METHODS: In January 2016, our institution implemented an organization-wide thirty-second delayed cord clamping protocol. This retrospective cross-sectional study represents infants of mothers diagnosed with pre-gestational diabetes who delivered before and after protocol implementation. The study period was from October 2014 to August 2017. The primary outcome was peak neonatal transcutaneous bilirubin (mg/dL) level during neonatal hospital stay. The secondary outcomes included neonatal serum bilirubin (mg/dL), jaundice requiring phototherapy, hypoglycemia, polycythemia, respiratory distress, and neonatal intensive care unit (NICU) admission. A subgroup analysis for outcomes stratified by type of pre-gestational diabetes was also performed. RESULTS: 145 patients were included in the final analysis. The mean peak neonatal transcutaneous bilirubin level was 10.1 mg/dL ± 3.4 mg/dL for immediate cord clamping and 9.5 mg/dL ± 3.4 mg/dL for delayed cord clamping (p = .25). There were no significant differences between groups for neonatal jaundice requiring phototherapy, hypoglycemia, polycythemia, respiratory distress, or NICU admission. No differences were observed in neonatal outcome by subgroup analysis of pre-gestational diabetes type. CONCLUSION: In our study, there was no significant increase in peak neonatal transcutaneous bilirubin in term (≥37 week) infants of mothers with pre-gestational diabetes after undergoing thirty-seconds of delayed cord clamping. In the absence of contraindications, we advocate for continued use of delayed cord clamping for these infants.

Effects of co-administration of vitamin E and lithium chloride on chronic constriction injury-induced neuropathy in male Wistar rats: Focus on antioxidant and anti-inflammatory mechanisms.

OBJECTIVES: This study investigated the antinociceptive effects of co-administration of lithium chloride (LiCl) and vitamin E (Vit E) on chronic constriction injury (CCI)-induced peripheral neuropathy in male Wistar rats. It further explored the anti-inflammatory and neuroprotective properties of LiCl and Vit E, which may be complementary to the antinociceptive effects of the two substances. METHODS: Thirty-six male Wistar rats, 190.00 ± 10.00 g of body weight were randomly assigned to 6 experimental groups and administered with normal saline, Vit E, LiCl, or their combination, once daily for 21 days. CCI was used to induce neuropathic pain (NP) and mechanical allodynia was assessed using von Frey filaments and pinprick test. Open field maze (OFM) was used to assess the exploratory behavior. Biochemical parameters were assessed in the dorsal root ganglion after 21 days of treatment. RESULTS: Mechanical allodynia was developed in rats following CCI. Co-administration of LiCl and Vit E synergistically reduced mechanical hyperalgesia in rats which were significantly different compared with the single administration of either Vit E or LiCl. Combined doses of Vit E and LiCl significantly increases the explorative behavior in the OFM. CCI increased malondialdehyde (MDA), tumor necrotic factor-alpha (TNF-α), calcitonin gene-related polypeptide, calcium ion (Ca2+ ), and reduced superoxide dismutase (SOD) activities. Co-administration of LiCl and Vit E significantly reduced MDA, TNF-α, but increased SOD compared with ligated control. DISCUSSION: The findings revealed that the synergistic effects of the co-administration of Vit E and LiCl in ameliorating NP are mediated by their anti-inflammatory and antioxidant properties.

Effects of Placental Transfusion on Late Preterm Infants Admitted to a Mother-Baby Unit.

OBJECTIVE: Well-appearing late preterm infants admitted to a mother baby unit may benefit from either delayed cord clamping (DCC) or umbilical cord milking (UCM). However, there are concerns of adverse effects of increased blood volume such as polycythemia and hyperbilirubinemia. The purpose of this study is to examine the short-term effects of placental transfusion on late preterm infants born between 350/7 and 366/7 weeks of gestation. STUDY DESIGN: In this pre- and postimplementation retrospective cohort study, we compared late preterm infants who received placental transfusion (161 infants, DCC/UCM group) during a 2-year period after guideline implementation (postimplementation period: August 1, 2017, to July 31, 2019) to infants who had immediate cord clamping (118 infants, ICC group) born during a 2-year period before implementation (preimplementation period: August 1, 2015, to July 31, 2017). RESULTS: The mean hematocrit after birth was significantly higher in the DCC/UCM group. Fewer infants had a hematocrit <40% after birth in the DCC/UCM group compared with the ICC group. The incidence of hyperbilirubinemia needing phototherapy, neonatal intensive care unit (NICU) admissions, or readmissions to the hospital for phototherapy was similar between the groups. Fewer infants in the DCC/UCM group were admitted to the NICU primarily for respiratory distress. Symptomatic polycythemia did not occur in either group. Median hospital length of stay was 3 days for both groups. CONCLUSION: Placental transfusion (DCC or UCM) in late preterm infants admitted to a mother baby unit was not associated with increased incidence of hyperbilirubinemia needing phototherapy, symptomatic polycythemia, NICU admissions, or readmissions to the hospital for phototherapy. KEY POINTS: · Placental transfusion was feasible in late preterm infants.. · Placental transfusion resulted in higher mean hematocrit after birth.. · Placental transfusion did not increase the need for phototherapy.. · Fewer admissions to the NICU for respiratory distress were noted in the placental transfusion group..

Effect of delayed cord clamping on jaundice and hypoglycemia in the neonates of mothers with gestational diabetes mellitus.

OBJECTIVE: To study the effect of delayed cord clamping (DCC) on the bilirubin levels and hypoglycemia in neonates with diabetic mothers (NDMs). METHODS: This is a comparison between a prospective cohort and a historical control cohort. Women with gestational diabetes mellitus who performed DCC were enrolled into the prospective cohort (n = 156), and those who performed early cord clamping (ECC) were enrolled into the historical control cohort (n = 161). RESULTS: NDMs who received DCC had higher transcutaneous bilirubin than those in the ECC group whether maternal glycemic control was good or poor. DCC increased the rate of neonatal hyperbilirubinemia and phototherapy when maternal blood glucose was well controlled but not when it was poorly controlled. No differences were found in initial blood glucose levels on days 1 to 3 of life between the two groups. CONCLUSION: Delayed cord clamping increased bilirubin levels, the risk of neonatal hyperbilirubinemia, and phototherapy in IDMs without improved initial blood glucose levels. Therefore, DCC was not recommended in NDMs.