Real-time analgesic efficacy and factors determining drug requirements of combined spinal-epidural analgesia for labor: a prospective cohort study.

PURPOSE: Combined spinal-epidural analgesia (CSEA) is effective but not sufficient for labor pain. This study was conducted to assess the real-time analgesic efficacy, side effects of anesthetic drug dosage, and maternal satisfaction in labor to provide reference for the optimization of labor analgesia. METHODS: This was a prospective, cohort, single-center study that included 3020 women who received CSEA for labor analgesia. The visual analogue scale (VAS) for labor pain, real-time anesthetic drug dosage, side effects, adverse labor outcomes, factors influencing average drug dosage, and maternal satisfaction with CSEA were assessed. RESULTS: Overall, the VAS labor pain score was lowest at the first hour after the anesthesia was given. After 4 h for primiparas and 3 h for multiparas, the VAS score was greater than 3 but the anesthetic drug dosage did not reach the maximum allowed dosage at the same time. The average anesthetic drug dosage was positively correlated with fever, urinary retention, uterine atony, prolonged active phase, prolonged second stage, assisted vaginal delivery, and postpartum hemorrhage. The average anesthetic drug dosage was the highest in women ≤ 20 years old, those with a body mass index (BMI) ≥ 24.9 kg/m2, and those with a primary or secondary education level. CONCLUSION: Appropriate age guidance and emphasis on education of labor analgesia, weight management during pregnancy, and real-time anesthetic dosage adjustment during labor based on VAS pain score may have positive effects on the satisfaction of labor analgesia. CLINICAL TRIAL NUMBER AND REGISTRY: Clinicaltrials.gov (ChiCTR2100051809).

Tumor microenvironment activation amplify oxidative stress promoting tumor energy remodeling for mild photothermal therapy and cuproptosis.

Tumor metabolic reprogramming requires high levels of adenosine triphosphate (ATP) to maintain treatment resistance, which poses major challenges to chemotherapy and photothermal therapy. Especially, high levels of ATP promote copper ion efflux for limiting the curative effect of cuproptosis. Here, an H2S-responsive mesoporous Cu2Cl(OH)3-loading chemotherapeutic cisplatin (CDDP) was synthesized, and the final nanoparticle, CDDP@Cu2Cl(OH)3-CDs (CDCuCDs), was encapsulated by electrostatic action with carbon dots (CDs). CDCuCDs reacted with overproduction H2S in colon tumor to produce photothermic copper sulfide for photothermal therapy. CDDP was released by lysis to achieve chemotherapeutic effects. Importantly, CDDP elevated H2O2 levels in cells through a cascade reaction and continuously transforms H2O2 into highly cytotoxic •OH through chemodynamic therapy between H2O2 and Cu+, which enables nanoparticles to generate •OH and improve the chemotherapeutic efficacy. Highly toxic •OH disrupts mitochondrial homeostasis, prohibiting it from performing normal energy-supplying functions. Down-regulated ATP inhibits heat shock protein expression, which promotes the therapeutic effect of mild photothermal therapy and reduces the efflux of intracellular copper ions, thus improving the therapeutic effect of cuproptosis. Our research provides a potential therapeutic strategy using overproduction H2S responses in tumors, allowing tumor microenvironment-activated •OH nanogenerators to promote tumor energy remodeling for cancer treatment.

Risk factors analysis and multidisciplinary team first-aid simulation training for umbilical cord prolapse can improve neonatal outcomes.

OBJECTIVE: In the present study, we sought to identify risk factors for umbilical cord prolapse (UCP) and adapt the multidisciplinary team (MDT) first-aid simulation training for UCP patients. We evaluated the usefulness of the MDT first-aid simulation by comparing delivery outcomes for UCP patients before and after its implementation. MATERIAL AND METHODS: A retrospective review was conducted on 149 UCP cases (48 overt and 101 occult) and 298 control deliveries that occurred at the Third Affiliated Hospital of Sun Yat-sen University from January 1998 to December 2022. Patient data were compared between the groups. One-way analysis of variance (ANOVA) was used for means comparison, and the chi-square test was used for categorical data. Univariate and multivariate logistic regression analyses were performed to identify factors significantly associated with UCP. RESULTS: Overt UCP was strongly associated with all adverse delivery outcomes. Both univariate and multivariate analyses identified multiparity, breech presentation, polyhydramnios, and low birth weight as independent risk factors for overt UCP (all odds ratios [OR] > 1; all p < 0.05). Preterm labor and abnormal placental cord insertion were identified as independent risk factors for occult UCP (all OR > 1; all p < 0.05). After 2014, when obstetrical staff received MDT first-aid simulation training, patients with overt UCP experienced shorter decision-to-delivery intervals due to more timely cesarean sections. They also had higher Apgar scores at 1, 5, and 10 min, and lower admission rates to the neonatal intensive care unit compared to patients before 2014 (all p < 0.05). CONCLUSION: MDT first-aid simulation training for overt UCP can improve neonatal outcomes. However, medical simulation training efforts should initially focus on the early identification of risk factors for both overt and occult UCP.

Overt umbilical cord prolapse (UCP) is an obstetric emergency that can lead to adverse delivery outcomes. Early identification of risk factors for both overt and occult UCP is beneficial for facilitating early interventions. Multidisciplinary team first-aid simulation training specifically for overt UCP has been shown to effectively improve neonatal outcomes.

Ganoderic acid A mitigates dopaminergic neuron ferroptosis via inhibiting NCOA4-mediated ferritinophagy in Parkinson's disease mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum, a renowned tonic traditional Chinese medicine, is widely recognized for the exceptional activity in soothing nerves and nourishing the brain. It has been extensively employed to alleviate various neurological disorders, notably Parkinson's disease (PD). AIM OF THE STUDY: To appraise the antiparkinsonian effect of GAA, the main bioactive constituent of G. lucidum, and clarify the molecular mechanism through the perspective of ferritinophagy-mediated dopaminergic neuron ferroptosis. MATERIALS AND METHODS: PD mouse and cell models were established using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP+), respectively. Cell viability, behavioral tests and immunofluorescence analysis were performed to evaluate the neurotoxicity, motor dysfunction and dopaminergic loss, respectively. Biochemical assay kits were used to determine the levels of iron, lipid reactive oxygen species (ROS), malondialdehyde (MDA), total ROS and glutathione (GSH). Western blot and immunofluorescence were applied to detect the expressions of nuclear receptor co-activator 4 (NCOA4), ferritin heavy chain 1 (FTH1), p62 and LC3B. Additionally, NCOA4-overexpressing plasmid vector was constructed to verify the inhibitory effect of GAA on the neurotoxicity and ferroptosis-related parameters in PD models. RESULTS: GAA significantly mitigated MPP+/MPTP-induced neurotoxicity, motor dysfunction and dopaminergic neuron loss (p＜0.01 or p＜0.05). In contrast to MPP+/MPTP treatment, GAA treatment decreased the levels of iron, MDA, lipid and total ROS, while increasing the GSH level. GAA also reduced the levels of NCOA4 and LC3B, and enhanced the expressions of FTH1 and p62 in PD models (p＜0.01 or p＜0.05). However, the protective effect of GAA against the neurotoxicity, NCOA4-mediated ferritinophagy and ferroptosis in PD model was abolished by the overexpression of NCOA4 (p＜0.01). CONCLUSION: GAA exerted a protective effect on PD, and this effect was achieved by suppressing dopaminergic neuron ferroptosis through the inhibition of NCOA4-mediated ferritinophagy.

H2S-driven chemotherapy and mild photothermal therapy induced mitochondrial reprogramming to promote cuproptosis.

The elevated level of hydrogen sulfide (H2S) in colon cancer hinders complete cure with a single therapy. However, excessive H2S also offers a treatment target. A multifunctional cascade bioreactor based on the H2S-responsive mesoporous Cu2Cl(OH)3-loaded hypoxic prodrug tirapazamine (TPZ), in which the outer layer was coated with hyaluronic acid (HA) to form TPZ@Cu2Cl(OH)3-HA (TCuH) nanoparticles (NPs), demonstrated a synergistic antitumor effect through combining the H2S-driven cuproptosis and mild photothermal therapy. The HA coating endowed the NPs with targeting delivery to enhance drug accumulation in the tumor tissue. The presence of both the high level of H2S and the near-infrared II (NIR II) irradiation achieved the in situ generation of photothermic agent copper sulfide (Cu9S8) from the TCuH, followed with the release of TPZ. The depletion of H2S stimulated consumption of oxygen, resulting in hypoxic state and mitochondrial reprogramming. The hypoxic state activated prodrug TPZ to activated TPZ (TPZ-ed) for chemotherapy in turn. Furthermore, the exacerbated hypoxia inhibited the synthesis of adenosine triphosphate, decreasing expression of heat shock proteins and subsequently improving the photothermal therapy. The enriched Cu2+ induced not only cuproptosis by promoting lipoacylated dihydrolipoamide S-acetyltransferase (DLAT) heteromerization but also performed chemodynamic therapy though catalyzing H2O2 to produce highly toxic hydroxyl radicals ·OH. Therefore, the nanoparticles TCuH offer a versatile platform to exert copper-related synergistic antitumor therapy.

A study of forensic genetics: ITO index distribution and kinship judgment between two individuals.

According to Mendel's law of genetic separation, there must be a certain blood relationship between members of the same family, and two individuals with blood relations must have the following three situations, that is, there are two homologous genes (I denotes), one homologous gene (T denotes), and no homologous genes (O denotes), which is the ITO index for calculating the blood relationship between two individuals. The AGGU Expressmarker 22 kit, ABI 3500 genetic analyzer, and GeneMapper ID-X v1.5 software were used to statistically analyze the ITO index of the gene locus of 5 kinds of samples, 28 pairs of monozygotic twins (MT), 4,000 pairs of parent-offspring (PO), 392 pairs of full sibling (FS), 138 pairs of half-siblings (HS) (including grandchildren, uncles, and nephews) and 3,500 pairs of unrelated individuals (UI). Observing the median distribution of ITO index found that from MT, PO, FS, HS to UI, the more distant the kinship, the smaller the ITO index. Full sibling index (FSI)/half-sibling index (HSI) ≥ 1 can be used as the FS discriminant standard, FSI/HSI < 1 can be used as the HS discriminant standard. According to the distance of kinship, from the direction of MT, PO, FS, HS, and UI, the proportion of the maximum ITO index of the same type of sample in the true kinship index item showed a decreasing trend. ITO index is an important statistical means to identify the kinship between two individuals, according to which the ITO index can accurately determine the kinship between individuals, which has high application value. MT index is not 0 to identify relatives as MT, PO index is an important indicator to distinguish between relatives as PO and FS. The critical values of ITO index discriminant values for UI and HS need to be further studied.