ParaCPI: A Parallel Graph Convolutional Network for Compound-Protein Interaction Prediction.

Identifying compound-protein interactions (CPIs) is critical in drug discovery, as accurate prediction of CPIs can remarkably reduce the time and cost of new drug development. The rapid growth of existing biological knowledge has opened up possibilities for leveraging known biological knowledge to predict unknown CPIs. However, existing CPI prediction models still fall short of meeting the needs of practical drug discovery applications. A novel parallel graph convolutional network model for CPI prediction (ParaCPI) is proposed in this study. This model constructs feature representation of compounds using a unique approach to predict unknown CPIs from known CPI data more effectively. Experiments are conducted on five public datasets, and the results are compared with current state-of-the-art (SOTA) models under three different experimental settings to evaluate the model's performance. In the three cold-start settings, ParaCPI achieves an average performance gain of 26.75%, 23.84%, and 14.68% in terms of area under the curve compared with the other SOTA models. In addition, the results of the experiments in the case study show ParaCPI's superior ability to predict unknown CPIs based on known data, with higher accuracy and stronger generalization compared with the SOTA models. Researchers can leverage ParaCPI to accelerate the drug discovery process.

Influences of elevational gradient on flower size and number of Gentiana lawrencei var. farreri.

Plants can adapt to environmental changes by adjusting their functional traits and biomass allocation. The size and number of flowers are functional traits related to plant reproduction. Life history theory predicts that there is a trade-off between flower size and number, and the trade-off can potentially explain the adaptability of plants. Elevation gradients in mountains provide a unique opportunity to test how plants will respond to climate change. In this study, we tried to better explain the adaptability of the alpine plant Gentiana lawrencei var. farreri in response to climate change. We measured the flower size and number, individual size, and reproductive allocation of G. lawrencei var. farreri during the flowering period along an elevation gradient from 3200 to 4000 m, and explored their relationships using linear mixed-effect models and the structural equation model. We found that with elevation increasing, individual size and flower number decreased and flower size increased, while reproductive allocation remained unchanged. Individual size positively affected flower number, but was not related to flower size; reproductive allocation positively affected flower size, but was not related to flower number; there is a clear trade-off between flower size and number. We also found that elevation decreased flower number indirectly via directly reducing individual size. In sum, this study suggests that G. lawrencei var. farreri can adapt to alpine environments by the synergies or trade-offs among individual size, reproductive allocation, flower size, and flower number. This study increases our understanding of the adaptation mechanisms of alpine plants to climate change in alpine environments.

The transversus abdominis plane block in conjunction with intrathecal morphine use after cesarean section in women with severe pre-eclampsia: a randomized controlled trial.

BACKGROUND: The transversus abdominis plane (TAP) block in conjunction with intrathecal morphine has been demonstrated to provide more superior postcesarean analgesia to intrathecal morphine alone. However, the analgesia efficacy of their conjunction has not been demonstrated in patients with severe pre-eclampsia. The study aimed to compare the postcesarean analgesia of TAP block in conjunction with intrathecal morphine versus intrathecal morphine alone in women with severe pre-eclampsia. METHODS: Pregnant women with severe pre-eclampsia undergoing planned cesarean section were randomly allocated into 2 groups to receive TAP block with 20 ml of 0.35% Ropivacaine (TAP group) or with the same volume of 0.9% saline (Sham group) after undergoing elective cesarean section under spinal anaesthesia with 15 mg of 0.5% Ropivacaine plus 0.1 mg of morphine. The outcomes for this analysis include the visual analog scale (VAS) pain score at rest and with movement at 4,8,12,24 h after TAP block was performed, times of use of intravenous patient-controlled analgesia (PCA) within 12 h after anesthesia, the occurrence of maternal side effects, maternal satisfaction, and Apgar score at 1 and 5 min of newborns. RESULTS: 119 subjects receive TAP block with 0.35% Ropivacaine (n = 59)or 0.9% saline (n = 60). At 4,8, 12 h after TAP block, the TAP group reported lower VAS score at rest [at 4 h: 1(0,1) vs. 1(1,2), P < 0.001; at 8 h:1(1,1) vs. 1(1.5,2),P < 0.001; at 12 h:1(1,2) vs. 2(1,2),P = 0.001] and higher satisfaction [53(89.9%) vs.45(75.0%), P < 0.05]. There were no differences between groups in VAS score at 24 h at rest and at all time points above with movement, times of use of PCA within 12 h after anesthesia, maternal side-effect, and Apgar score at 1 and 5 min of newborns. CONCLUSIONS: In conclusion, The TAP block performed in conjunction with intrathecal morphine may not reduce opioid consumption, but it could reduce VAS scores at rest in the first 12 h after cesarean section in women with severe pre-eclampsia, and improve maternal satisfaction, which is worthy of clinical promotion. TRIAL REGISTRATION: Registered at Chinese Clinical Trial Registry( http://www.chictr.org.cn ) on 13/12/2021: ChiCTR2100054293.

The Effect of Propofol plus Remifentanil for PostoperativePain and Heart Rate Management in Patients Undergoing Abdominal Hysterectomy.

Purpose: To explore the effect of propofol plus remifentanil for postoperative pain and heart rate management in patients undergoing abdominal hysterectomy. Methods: In this prospective randomized controlled study, 96 patients who underwent abdominal hysterectomy in an affiliated hospital of Fujian Medical University from April 2016 to April 2017 were recruited and randomized into the study group (n = 48) and control group (n = 48) via the random number table method. The control group received remifentanil for anesthesia, and the study group was given propofol plus remifentanil. The postoperative pain and heart rates of patients were compared between the two groups. Results: No significant difference was observed in the heart rate and adrenaline values between the two groups before anesthesia, and the study group had significantly lower adrenaline values and heart rates intraoperatively and 15 min after operation than the control group. Patients in the study group showed shorter time-lapse before independent breathing recovery, extubation, and resuscitation compared to those in the control group. The study group received less patient-controlled intravenous analgesia (PCIA) as compared to the study group within 48 h after operation. In the study group, the numeric rating scale (NRS) scores within 1 h, 2 h, 6 h, 8 h, and 12 h after operation were significantly lower than those in the control group (P < 0.001). Propofol plus remifentanil offer a viable alternative for postoperative pain management and stress alleviation after abdominal hysterectomy with a high safety profile. Further clinical trials are, however, required prior to clinical promotion.

Risk factors associated with reintubations in children undergoing foreign body removal using flexible bronchoscopy: a single-center retrospective cross-sectional study.

BACKGROUND: Reintubation is a severe complication during foreign body (FB) removal that uses flexible bronchoscopy. OBJECTIVE: To investigate the incidence and risk factors for reintubations in children undergoing FB extraction by flexible bronchoscopy in a single center. DESIGN: A retrospective cross-sectional study. SETTING: All children with foreign body aspiration at Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University from January 2015 to December 2020. PATIENTS: Children with FB removal using a flexible bronchoscopy were enrolled in the trial according to the inclusion criteria. MEASUREMENTS: Both multivariable and logistic regression analyses were used to analyze the association between characteristic data and reintubations. The results were presented as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: In total, 244 patients met with the inclusion criteria and were included in the analysis. Among those participants, 28 children (11.5%) underwent reintubations after FB removal by flexible bronchoscopy. Independent factors associated with reintubations were identified as operative time ≥ 60 min [OR: 3.68, 95% CI (1.64-8.82)] and ASA ≥ III [OR: 5.7, 95% CI (1.23-26.4)]. CONCLUSIONS: Children undergoing FB removal by a flexible bronchoscopy may encounter with a high incidence of postoperative reintubations. Both long operative duration and a severe physical status cause a growing risk of reintubations.

Developmental Cardiotoxicity and Hepatotoxicity of Flurbiprofen Axetil to Zebrafish Embryo.

Flurbiprofen axetil (FA) is a nonsteroidal targeted analgesic and widely used for postoperative analgesia and cancer analgesia. Extensive works have been done in the evaluation of FA's clinical analgesic effect on adults. Along with the increase of FA usage, the potential toxicity and molecular mechanism in embryo development need to be better understood. In this article, multiple embryonic development indexes of zebrafish were introduced to evaluate the FA toxicity to provide clinical guidance for gravidas medicine. We performed a zebrafish embryo toxicity (ZFET) test by exposing embryos to a series of concentration gradients of FA medium starting from 24 hours postfertilization (hpf). The mortality rate, hatching rate, and malformation rate of drug-treated zebrafish were assessed at 72, 96, and 120 hpf. Effects of ≤10% lethal concentration (LC10) of FA on embryogenesis were evaluated by eye area, body length, and yolk sac area. A 0.5 µg/mL or fewer FA treatment did not show any adverse effects, but the LC10 FA significantly caused zebrafish malformation. Organ disorders, including slow heart rate, enlarged pericardium, and liver atrophy, were found in the dysplasia individuals when compared with control. TUNEL assay suggested that apoptotic cells in malformation embryos were produced by FA and the increasing dosage exacerbated apoptosis. Quantitative real-time polymerase chain reaction revealed that expressions of cardiac development-associated transcription factors, liver development-related genes, and apoptosis regulating genes were aberrant. These results indicate that the ZFET can be applied in the FA toxicity test, and a low lethal dose of FA is harmful to zebrafish embryogenesis, especially in embryo carcinogenesis and hepatogenesis.

Nanoparticles Isolated From Porcine Bone Soup Ameliorated Dextran Sulfate Sodium-Induced Colitis and Regulated Gut Microbiota in Mice.

Daily foods contain a great number of self-assembled nanoparticles (NPs) which were incidentally produced during food processing. These food incidental NPs can directly access the human gastrointestinal tract in high frequency and large quantities. Limited reports were focused on whether and how these food incidental NPs affected the gastrointestinal tissues and gut microbiota. In the present study, bone soup and its NPs both significantly ameliorated colitis symptoms in dextran sulfate sodium (DSS)-induced mice and inhibited the release of pro-inflammatory cytokines. They also restored intestinal microbiota dysbiosis by improving the diversity and richness of intestinal microbiota and regulating community composition, such as a remarkable increase in Muribaculaceae, Alistipes, and Alloprevotella, and a decrease in Helicobacter. Moreover, the correlation analysis showed that pro-inflammatory cytokines were negatively correlated with Muribaculaceae, Alloprevotella, and Alistipes, but positively correlated with Helicobacter. These findings suggest that the food incidental NPs can influence human health through regulating the inflammation of the gastrointestinal tissues and the gut microbiota.

Effects of valerate on intestinal barrier function in cultured Caco-2 epithelial cell monolayers.

BACKGROUND: Short-chain fatty acids (SCFAs) are a group of microbial metabolites of undigested dietary fiber, protein and unabsorbed amino acids in the colon, well-known for their gut health promoting benefits. A relatively high intestinal level of valerate was found in the healthy human subjects. However, the intestinal protection effects and the underlying mechanism of valerate are waiting to be verified and elucidated. METHODS AND RESULTS: In the present study, valerate, a SCFAs mainly converted from proteins or amino acids, was demonstrated to promote intestinal barrier function at its physiological concentrations of 0-4 mM in the Caco-2 cell monolayer model of intestinal barrier using transepithelial electrical resistance (TEER) assay and paracellular permeability assay. Valerate achieved the maximum increase in the TEER at 2 mM and reduced the paracellular permeability. Its intestinal barrier function promoting activity is similar to that of butyrate, with a broader range of effective concentrations than the later. Through western blot analysis, this activity is linked to the valerate-induced AMPK activation and tight junctions (TJs) assembly, but not to the reinforced expression of TJs related proteins. CONCLUSIONS: It provides direct experimental evidence supporting valerate's function in intestinal health, implying the once under-valued function of valerate and its amino acid precursors. The valerate's role in regulating intestine homeostasis and its possible synergetic effects with other SCFAs warranted to be further investigated.

Use of intravenous lidocaine for dose reduction of propofol in paediatric colonoscopy patients: a randomised placebo-controlled study.

BACKGROUND: Propofol, a widely used sedative in endoscopic procedures, sometimes causes cardiopulmonary complications. Intravenous lidocaine can diminish visceral pain and decrease the dose of propofol. The purpose of this study was to assess the efficacy and safety of intravenous lidocaine in reducing propofol dosage during paediatric colonoscopy. METHODS: Forty children who underwent colonoscopy were divided into two groups. Lidocaine hydrochloride (1.5 mg/kg induction and 2 mg/kg/h maintenance) was given intravenously to the lidocaine group, and the same amount of saline was given to the control group after they received lidocaine induction. Propofol initial plasma concentration of 5 µg/mL was targeted, and the procedure was performed after the bispectral index value reached 55. The primary outcome was propofol requirement. RESULTS: The propofol requirement in the lidocaine group was decreased by 35.5% (128.6 ± 30.4 mg vs. 199.4 ± 57.6 mg; p < 0.001; 95%CI: - 100.60, - 41.02). The incidence of involuntary body movements was significantly lower in the lidocaine group (p = 0.028; OR = 0.17; 95%CI: 0.03, 0.92). The awakening time (p < 0.001; 95%CI: - 7.67, - 5.13) and recovery times (p < 0.001; 95%CI: - 7.45, - 4.35) were significantly lower in the lidocaine group. Pain was significantly less at 30 min and 60 min after the procedure in the lidocaine group (0 [0-4] vs. 3 [0-5], p < 0. 001; 0 [0-2] vs. 1 [0-3], p = 0.001). There was no difference in the incidence of bradycardia, hypotension, or hypoxia between the two groups. CONCLUSIONS: For colonoscopy procedures in paediatric patients, intravenous lidocaine reduces the amount of propofol needed, provides better sedation and postprocedural pain management, as well as a reduction in recovery time. TRIAL REGISTRATION: The trial was registered on November 6, 2020 at China Clinical Trials Registration Center ( www.chictr.org.cn ) ref.: ChiCTR 2,000,039,706.

Comparison between pressure-controlled ventilation with volume-guaranteed mode and volume-controlled mode in one-lung ventilation in infants undergoing video-assisted thoracoscopic surgery.

BACKGROUND: The appropriate ventilation mode for one-lung ventilation (OLV) in infants undergoing video-assisted thoracoscopic surgery (VATS) remains controversial. Here we investigated the effect of ventilatory mode "pressure-controlled ventilation-volume guaranteed" (PCV-VG) on the airway pressures and oxygenation parameters by comparing it with volume-controlled ventilation (VCV). METHODS: We retrospectively analyzed the clinical data of infants aged 2 to 12 months who underwent extratracheal bronchial blockage for OLV in our center between January 2017 and August 2020. The infants were divided into two groups according to the OLV pattern: group G (n=30, receiving PCV-VG) and group V (n=28, receiving VCV). Mean arterial pressure (MAP), heart rate (HR), maximum inspiratory pressure (Ppeak), mean airway pressure (Pmean), dynamic compliance (Cdyn), partial arterial pressure of oxygen (PaO2) was measured and compared between these two groups 10 min before OLV (T1), 30 min after the onset of OLV (T2) and 15 min after OLV (T3). The possible occurrence of hypoxemia and hypotension during OLV was monitored. RESULTS: Compared to group V, group G had significantly higher PaO2and Cdyn (both P<0.05) and significantly lower Ppeak and Pmean (both P<0.05) in T2. However, all indicators did not show significant differences between these two groups at T1 and T3 (all P>0.05). The incidence of hypoxemia was significantly higher in group V than in group G (P<0.05), while the difference in the incidence of hypotension was not statistically significant (P>0.05). CONCLUSIONS: Mechanical ventilation using the PCV-VG mode is possible in infants when performing OLV during VATS. Compared to VCV, PCV-VG can offer lower Ppeak and Pmean, improve lung compliance, and achieve better oxygenation.

Intervention of WeChat Group Guidance in Rapid Rehabilitation after Gynecological Laparoscopic Surgery.

Gynecological laparoscopic surgery is the current routine treatment. Although the injury is relatively small, it is still a traumatic operation and also increases the recovery speed of patients. This paper mainly explores the intervention effect of rapid rehabilitation after gynecological laparoscopic surgery by means of WeChat group guidance based on the information adoption model and UTAUT model. Gynecological patients who underwent laparoscopic surgery and met the inclusion and exclusion conditions in a provincial maternal and child health hospital were selected as the research objects. The WeChat intervention group was compared with the nonintervention group, and the oral description score (VRS), comfort score (BCS), and 40-item recovery quality rating scale (QoR-40) were used as the scoring criteria. The results showed that the postoperative VRS and BCS scores in the WeChat intervention group were significantly lower than those in the nonintervention group. The total score of QoR-40 in both groups decreased compared with that before operation, reached the lowest on the first day after operation, and began to rise from the second day. This result is consistent with the patient's postoperative recovery process. After operation, the total score of the WeChat intervention group on days 1 and 2 was higher than that of the non-WeChat intervention group. By comparing the results of the patient's postoperative oral description score (VRS), comfort score (BCS), 40-item recovery quality score scale (QoR-40), etc., it can be shown that the overall recovery quality of the WeChat intervention group was better during these two days. In each section, the oral description score (VRS) and the 40-item recovery quality score scale (QoR-40) indicated that the pain sensation and emotional state scores of patients in the WeChat intervention group were higher than those in the nonintervention group, while the comfort score (BCS) was lower, indicating better comfort in the WeChat intervention group.

General versus general anaesthesia combined with caudal block in laparoscopic-assisted Soave pull-through of Hirschsprung disease: a retrospective study.

BACKGROUND: Caudal block is one of the most preferred regional anesthesia for sub-umbilical region surgeries in the pediatric population. However, few studies are available on caudal block performed in laparoscopic-assisted Soave pull-through of Hirschsprung disease (HD). We aimed to compare general anesthesia (GA) and general anesthesia combined with caudal block (GA + CA) in laparoscopic-assisted Soave pull-through of HD. METHODS: A retrospective review was performed in children with HD operated in our hospital between 2017 and 2020. Patients were divided into the GA and GA + CA group. The primary outcome was the duration of operation, and secondary outcomes included intraoperative hemodynamic changes, the Face, Legs, Activity, Cry, Consolability (FLACC) scale, dose of anesthetics, and incidence of side effects. RESULTS: A total of 47 children with HD were included in the study, including 20 in the GA group and 27 in the GA + CA Group. The two groups were similar in age, gender, weight and type of HD (P > 0.05). The GA + CA group had significantly shorter duration of operation (especially the transanal operation time) (median 1.20 h vs. 0.83 h, P < 0.01) and recovery time (mean 18.05 min vs. 11.89 min, P < 0.01). The mean doses of sufentanil and rocuronium bromide during the procedure and FLACC scores at 1 h and 6 h after surgery were also lower in the GA + CA group (p < 0.01). The hemodynamic changes in the GA + CA group were more stable at time of t2 (during transanal operation) and t3 (10 min after transanal operation), but there was no significant difference in the incidence of postoperative side effects between the two groups (P = 1.000). CONCLUSION: General anesthesia combined with caudal block can shorten the duration of operation, and provide more stable intraoperative hemodynamics and better postoperative analgesia.

A randomized trial of the dural puncture epidural technique combined with programmed intermittent epidural boluses for labor analgesia.

BACKGROUND: Continuous epidural infusion (CEI) can provide analgesia during labor. The dural puncture epidural (DPE) technique is used to accelerate the onset of neuraxia anesthesia. The primary objective of this study was to compare the percentage of patients that received adequate labor analgesia following an injection of 0.08% epidural ropivacaine via the DPE and CEI techniques combined with the PIEB mode of maintenance. METHODS: Patients who were laboring were randomly allocated to receive either CEI + PIEB or DPE + PIEB. Subjects indicated a VAS score immediately prior to epidural placement, and parturients with a VAS score of ≤50 mm were excluded. A 25-gauge needle was used for dural puncture. Analgesia was provided with 10 mL of 0.08% ropivacaine and 0.4 µg/mL of sufentanil, and was maintained at 10 mL/h in both groups with the same solution. All pumps were programmed for patient-controlled epidural analgesia (PCEA) boluses of 5 mL with a 20-minute lockout. VAS measurements were collected at 2-minute intervals for up to 20 minutes after initiation of the epidural bolus. The median time to adequate analgesia was analyzed using Kaplan-Meier curves and Cox proportional hazard models. RESULTS: Data were collected and analyzed from 200 participants (n=100 per group). Adequate analgesia at 10 minutes was higher in the DPE + PIEB group compared to the CEI + PIEB group (DPE + PIEB =58.4% vs. CEI + PIEB =41.6%; P=0.007). The DPE + PIEB group also had a shorter median time to adequate analgesia [median (95% confidence interval (CI), 8 minutes (7-9 minutes) vs. 12 minutes (10-14 minutes)] compared to the CEI + PIEB group [hazard ratio (HR) =1.488; 95% CI, 1.105-2.002; P=0.002]. CONCLUSIONS: The percentage of parturients with adequate analgesia at 10 minutes was higher with DPE + PIEB compared to CEI + PIEB. Furthermore, the DPE + PIEB mode was associated with a faster time to a VAS score ≤30 mm.

Propofol suppresses cell viability, cell cycle progression and motility and induces cell apoptosis of ovarian cancer cells through suppressing MEK/ERK signaling via targeting circVPS13C/miR-145 axis.

BACKGROUND: Propofol is a kind of common intravenous anaesthetic agent that plays an anti-tumor role in a variety of cancers, including ovarian cancer. However, the working mechanism of Propofol in ovarian cancer needs further exploration. METHODS: The viability and metastasis of ovarian cancer cells were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays. Flow cytometry was used to evaluate the cell cycle and apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the abundance of circular RNA vacuolar protein sorting 13 homolog C (circVPS13C) and microRNA-145 (miR-145). The target relationship between miR-145 and circVPS13C was predicted by circinteractome database and verified by dual-luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and RNA-pull down assay. Western blot assay was used to detect the levels of phosphorylated extracellular regulated MAP kinase (p-ERK), ERK, p-MAP kinse-ERK kinase (p-MEK) and MEK, in ovarian cancer cells. RESULTS: Propofol treatment suppressed the viability, cell cycle and motility and elevated the apoptosis rate of ovarian cancer cells. Propofol up-regulated miR-145 in a dose-dependent manner. Propofol exerted an anti-tumor role partly through up-regulating miR-145. MiR-145 was a direct target of circVPS13C. Propofol suppressed the progression of ovarian cancer through up-regulating miR-145 via suppressing circVPS13C. Propofol functioned through circVPS13C/miR-145/MEK/ERK signaling in ovarian cancer cells. CONCLUSION: Propofol suppressed the proliferation, cell cycle, migration and invasion and induced the apoptosis of ovarian cancer cells through circVPS13C/miR-145/MEK/ERK signaling in vitro.

Autophagic Network Analysis of the Dual Effect of Sevoflurane on Neurons Associated with GABARAPL1 and 2.

BACKGROUND: Sevoflurane is commonly used as a general anesthetic in neonates to aged patients. Preconditioning or postconditioning with sevoflurane protects neurons from excitotoxic injury. Conversely, sevoflurane exposure induces neurotoxicity during early or late life. However, little is known about the underlying mechanism of the dual effect of sevoflurane on neurons. Autophagy is believed to control neuronal homeostasis. We hypothesized that autophagy determined the dual effect of sevoflurane on neurons. METHODS: DTome was used to identify the direct protein target (DPT) of sevoflurane. The STRING database was employed to investigate the proteins associated with the DPTs. Protein-protein interaction was assessed using Cytoscape. WebGestalt was used to analyze gene set enrichment. The linkage between candidate genes and autophagy was identified using GeneCards. RESULTS: This study found that 23 essential DPTs of sevoflurane interacted with 77 proteins from the STRING database. GABARAPL1 and 2, both of which are DPT- and autophagy-associated proteins, were significantly expressed in the brain and enriched in GABAergic synapses. CONCLUSIONS: Taken together, our findings showed that the network of sevoflurane-DPT-GABARAPL1 and 2 is related to the dual effect of sevoflurane on neurons.