Studies Related to the Involvement of EsA in Improving Intestinal Inflammation in Acute Pancreatitis via the NF-κB Pathway.

Background: Acute pancreatitis (AP) is a clinically frequent acute abdominal condition, which refers to an inflammatory response syndrome of edema, bleeding, and even necrosis caused by abnormal activation of the pancreas's own digestive enzymes. Intestinal damage can occur early in the course of AP and is manifested by impaired intestinal mucosal barrier function, and inflammatory reactions of the intestinal mucosa, among other factors. It can cause translocation of intestinal bacteria and endotoxins, further aggravating the condition of AP. Therefore, actively protecting the intestinal mucosal barrier, controlling the progression of intestinal inflammation, and improving intestinal dynamics in the early stages of AP play an important role in enhancing the prognosis of AP. Methods: The viability and apoptosis of RAW264.7 cells treated with Esculentoside A (EsA) and/or lipopolysaccharide were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry, respectively. The expression of apoptosis-related proteins and NF-κB signaling pathway-related proteins were detected by western blot (WB). An enzyme-linked immunosorbent assay was used to measure TNF-α and IL-6 secretion. Results: In vitro experiments demonstrated that EsA not only promoted the apoptosis of inflammatory cells but also reduced the secretion of TNF-α and IL-6 in a dose-dependent manner. Additionally, it inhibited the activation of the NF-κB signaling pathway by decreasing the expression of phosphorylated-p65(p-p65) and elevating the expression of IκBα. Similarly, in vivo experiments using a rat AP model showed that EsA inhibited the expression of p-p65 elevating the expression of IκBα in the intestinal tissues of the rat AP model and promoting the apoptosis of inflammatory cells in the intestinal mucosa in vivo experiments, while improving the pathological outcome of the pancreatic and intestinal tissues. Conclusion: Our results suggest that EsA can reduce intestinal inflammation in the rat AP model and that EsA may be a candidate for treating intestinal inflammation in AP and further arresting AP progression.

Esculentoside A Alleviates Intestinal Dysmotility in Ulcerative Colitis by Regulating H2S/CSE and NO/nNOS Systems.

Background: Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that commonly affects the health of many individuals. Esculentoside A (EsA), a saponin extracted from the roots of Phytolacca esculenta, has antioxidative and anti-inflammatory effects against various diseases. Nonetheless, its role in UC is undetermined. Hence, in this study, we examined the therapeutic effects of EsA in UC. Methods: Primary intestinal neuronal cells (in vitro) were treated with lipopolysaccharide (LPS) to induce inflammatory injury. An in vivo UC rat model was created by the administration of dextran sulfate sodium (DSS) to rats, which were subsequently treated with different doses of EsA. The effects of EsA on intestinal motility, histological score, inflammatory response, hydrogen sulfide (H2S)/cystathionine γ-lyase (CSE) system, NO/neuronal nitric oxide synthase (nNOS) system, and LPS-induced primary intestinal neuronal cell viability loss, proliferation inhibition, and apoptosis were detected. Results: In vitro, EsA treatment increased the number of DSS-inhibited bowel movements and body weight, improved the histological score of colitis, and inhibited the inflammatory response by reducing IL-6 and TNF-α levels in rats. More importantly, EsA reduced the NO and H2S levels in serum and CSE, CBS, and nNOS expressions in the colon tissue. In vivo, EsA treatment eased the viability loss, proliferation inhibition, and apoptosis of LPS-stimulated primary intestinal neuronal cells, as well as inhibited the expressions of IL-6, TNF-α, CSE, CBS, and nNOS in cells. Conclusion: EsA improved intestinal motility and suppressed inflammatory response in DSS-induced UC, which may be mediated by H2S/CSE and NO/nNOS systems.

Mitochondrion-Localized SND1 Promotes Mitophagy and Liver Cancer Progression Through PGAM5.

Staphylococcal nuclease domain-containing protein 1 (SND1) is an evolutionarily conserved multifunctional protein that functions mainly in the nucleus and cytoplasm. However, whether SND1 regulates cellular activity through mitochondrial-related functions remains unclear. Herein, we demonstrate that SND1 is localized to mitochondria to promote phosphoglycerate mutase 5 (PGAM5)-mediated mitophagy. We find that SND1 is present in mitochondria based on mass spectrometry data and verified this phenomenon in different liver cancer cell types by performing organelle subcellular isolation. Specifically, The N-terminal amino acids 1-63 of SND1 serve as a mitochondrial targeting sequence (MTS), and the translocase of outer membrane 70 (TOM 70) promotes the import of SND1 into mitochondria. By immunoprecipitation-mass spectrometry (IP-MS), we find that SND1 interacts with PGAM5 in mitochondria and is crucial for the binding of PGAM5 to dynamin-related protein 1 (DRP1). Importantly, we demonstrate that PGAM5 and SND1-MTS are required for SND1-mediated mitophagy under FCCP and glucose deprivation treatment as well as for SND1-mediated cell proliferation and tumor growth both in vitro and in vivo. Aberrant expression of SND1 and PGAM5 predicts poor outcomes in hepatocellular carcinoma (HCC) patients. Taken together, these findings establish a previously unappreciated role of SND1 and the association of mitochondrion-localized SND1 with PGAM5 in mitophagy and tumor progression.

[IL-6 inhibits colonic longitudinal muscle contraction by inactivating L-type calcium channel in rats with pancreatitis].

The aim of this study was to investigate the effect of interleukin 6 (IL-6) on the contraction of colon longitudinal muscle strips in rats with acute pancreatitis (AP) and its underlying mechanism. Rat AP model was established by combined injection (i. p.) of ceruletide and lipopolysaccharide. The effect of IL-6 on spontaneous contraction of longitudinal smooth muscle strips of rat colon was observed by biological function experiment system. The level of serum IL-6 was detected by ELISA, the expression and distribution of IL-6 in colon were observed by histochemical staining, and the effect of IL-6 on L-type calcium channel in colon smooth muscle cells was observed by whole cell patch clamp technique. The results showed that, compared with the control group, AP group exhibited reduced contractile amplitude and longer contraction cycle of colon smooth muscle strips. IL-6 prolonged the contraction cycle of colon smooth muscle strips, but did not affect their spontaneous contraction amplitude. Serum IL-6 concentration in AP group was significantly higher than that in control group (P > 0.05). IL-6 was diffusely distributed in the colon of the control group, but the expression of IL-6 was significantly up-regulated in the colon gland, mucosa and submucosa of the AP group. IL-6 significantly decreased the peak current density of L-type calcium channel in rat colon smooth muscle cells. These results suggest that the colon motility of AP rats is weakened, and the mechanism may be that up-regulated IL-6 inactivates L-type voltage-dependent calcium channels, and then inhibits the contraction of colon longitudinal smooth muscle.

Oxidative stress and antioxidant status in a lizard Phrynocephalus vlangalii at different altitudes or acclimated to hypoxia.

Oxidative stress is a major challenge for the survival of animals living on plateaus; however, lifelong exposure to high altitudes could generate certain adaptabilities which make them more tolerant to these environments. The aim of the present study was to compare the oxidative stress and antioxidant status between low altitude (LA, 2900m) and high altitude (HA, 4200m) populations of Phrynocephalus vlangalii. The results showed that malondialdehyde levels in the HA populations decreased significantly in the brain, but markedly increased in the muscle and had no significant difference in the liver compared to LA populations. The activity of catalase in the brain was much higher in HA than LA. Except for total antioxidant capacity and glutathione reductase, other antioxidants were similar between the two populations in livers. By contrast, the levels of most antioxidants in muscle decreased markedly with elevation. We also explored the effects of hypoxia on oxidative damage and antioxidant defenses in P. vlangalii. The lizards were acclimated in a simulated hypoxic chamber (15% O2 and 8% O2) for 6weeks. The results showed that in the 8% O2 group, the levels of malondialdehyde, catalase, glutathione and total antioxidant capacity in the brain, and malondialdehyde, catalase and superoxide dismutase in the liver were significantly higher than the 15% O2 group. These findings indicate that in this species the oxidative stress and antioxidant capacity are subject to altitude and hypoxia and this lizard may have acquired some ability to deal with the oxidative stress.

[Low-dose ketamine combined with fentanyl for intravenous postoperative analgesia in elderly patients].

OBJECTIVE: To investigate the clinical efficacy of and complications arising from low-dose ketamine combined with fentanyl for intravenous postoperative analgesia in comparison with the exclusive use of fentanyl in elderly patients. METHODS: Eighty elderly patients were randomized into two equal groups following thoracoabdominal surgery, and received intravenous analgesia with the combination of 0.5 mg/ml ketamine, 5.0 microg/ml fentanyl and 50 microg/ml midazolam (KF group) and with 7.5 microg/ml fentanyl plus 50 microg/ml midazolam (FT group), respectively. The drugs used were diluted in 200 ml normal saline. For analgesic administration, a loading dose (2-4 ml) was given followed by a background infusion (2.5-3.5 ml), with patient-controlled bolus doses of 2.0-3.0 ml with lock-out time of 20 min via PCA pump (Automedical, Korea). The static pain score (VAS), sedation score, and incidences of nausea, vomiting, pruritus and hallucinations were recorded during the initial 48 h after the surgery. RESULTS: The total analgesic dosage and PCA dosage in the two groups were similar (P>0.05). With similar VAS in the two groups (P>0.05), the sedative effect in KF group was much better than that in FT group (P<0.05) during the initial 48 h postoperatively. The incidences of nausea, vomiting and itching were lower in KF group than in FT group (P<0.05), and no illusion was reported in two groups during the initial 48 h. CONCLUSION: For producing comparable postoperative analgesic effect, low-dose ketamine combined with fentanyl can markedly reduce fentanyl requirement in the elderly patients and lowers the incidences of nausea, vomiting and itching in comparison with the exclusive use of fentanyl.

[Effects of penehyclidine hydrochloride or atropine combined with neostigmine for antagonizing residual neuromuscular block on patient's hemodynamics].

OBJECTIVE: To investigate the effects of penehyclidine hydrochloride(PH)/atropine combined with neostigmine for antagonizing residual neuromuscular block on the hemodynamics. METHODS: Eighty patients with elective upper abdominal surgery were randomized equally into PH group and atropine group. Five minutes after the completion of surgery, PH 0.02 mg/kg (in PH group) or atropine 0.02 mg/kg (in atropine group) in combination with neostigime 0.03 mg/kg were given intravenously to reverse the residual neuromuscular block. The heart rate (HR), mean arterial pressure (MAP) and end-tidal CO(2) pressure (P(ET)CO(2)) were recorded 5 min before anesthesia induction, 1 min before injection and 2, 5, 10, and 15 min after injection, respectively. RESULTS: During the investigation, HR in PH group did not undergo conspicuous changes (P>0.05). HR after the injection was markedly faster than that before the injection in atropine group (P<0.01) and did not recover till 15 min after the injection (P>0.05). MAP and P(ET)CO(2) showed no evident changes and no significant difference was observed between the two groups during the investigation (P>0.05). CONCLUSION: Compared with atropine, PH does not obviously affect HR and BP, but atropine may accelerate HR.

[Management of hyperkalemia-induced cardiac arrest in anhepatic stage of orthotopic liver transplantation without venovenous bypass: report of 3 cases].

The causes of high serum potassium-induced cardiac arrest in anhepatic stage of orthotopic liver transplantation were analyzed in 3 cases without venovenous bypass, and the effectiveness of insulin was evaluated in correcting hyperkalemia during the anhepatic stage. To improve the survival rate of patients with such cardiac arrest, early cardiopulmonary resuscitation and timely defibrillation should be performed.

[Changes of oxygen cost of breathing in children and adult during anesthesia and surgery].

OBJECTIVE: To investigate the changes of oxygen cost of breathing (OCB) in children and adult during general anesthesia and surgery. METHODS: This study included 12 elective surgical children and 12 adult patients receiving cerebral surgery. Mechanical ventilation was given during general anesthesia and surgery, and the indices of hemodynamics and respiratory function were measured at 5 min before induction, 1 min before the start of surgery, 30, 60, 120 and 180 min after the start of surgery and at the end of surgery, respectively. RESULTS: Mean arterial pressure (MAP) in the 2 groups did not undergo any conspicuous changes during general anesthesia and surgery (P>0.05), and the heart rate in child group was markedly faster than that in adult group during the whole course (P<0.01). Oxygen consumption (VO2) in 2 groups at 1 min before the start of surgery and 30 min after the start of surgery was significantly higher than that at 5 min before induction (P<0.01), and at these two time points after induction, child group had much higher VO2 (P<0.05) but evidently lower OCB (P<0.01) than in adult group, the latter index remained low till 60 and 120 min after the start of surgery (P<0.05). CONCLUSION: During anesthesia and surgery, VO2 in child group can be much greater than that in Adult group, while OCB markedly lower.

[Ropivacaine or its combination with fentanyl for postoperative patient-controlled epidural analgesia].

OBJECTIVE: To investigate the pain-relieving effects of ropivacaine or its combination with fentanyl in postoperative patient-controlled epidural analgesia. METHODS: Sixty patients (ASA class I to II) scheduled for elective upper abdominal surgery were randomly divided into 4 groups (15 in each group) to receive 2.0 mg/ml ropivacaine (group R), 1.25 mg/ml ropivacaine plus 1.0 microg/ml fentanyl (group RF1), 1.0 mg/ml ropivacaine plus 2.0 microg/ml fentanyl (group RF2), and 1.0 mg/ml ropivacaine plus 4.0 microg/ml fentanyl (group RF4) respectively for patient-controlled analgesia. The bolus injection was set at 3.0 ml, lockout interval at 20 min, and background epidural infusion at 5.0 ml/h. Before and at 0, 6, 12, 24 and 48 h after the surgeries, the data including mean arterial pressure (MAP), heart rate (HR), cumulative consumption volume (CCV) of analgesic solution and visual analog scale (VAS) scores were recorded, observed and the adverse effects such as vomiting, nausea, pruritus, as well as the time of first excretion of intestinal gas. RESULTS: Compared with group R, significantly smaller CCV occurred in groups RF2, RF4 (P<0.01), and RF1 (P<0.05) at each time points postoperatively. No significant differences were noted between the groups in VAS scores. CONCLUSION: The 4 preparations are comparable in terms of analgesic efficacy and adverse effects, but in groups RF2 and RF4, the smaller doses have sufficed the needs.

[Anesthetic management during resection of intratracheal tumor: report of 23 cases].

OBJECTIVE: To summarize our experience in anaesthetic management during the resection of intratracheal tumor. METHODS: A retrospective analysis of the anaesthetic management was conducted in 23 cases of intratracheal tumor resection. The anaesthetic methods were determined according to the location of tumor, the degree of tracheal obstruction and the surgical procedures. RESULTS: No severe complications occurred in relation to the anesthetic procedures. During the operation, the saturation of pulse oxygen (SpO(2)) transiently decreased to below 90 % in 5 cases (21.7 %) but recovered to normal level by aspiration of airway secretions and/or lung inflation. Seventeen patients (73.9 %) were extubated after the operation and returned to the ward safely, while another 6 (26.1 %) were sent to intensive care unit and extubated within 24 h. CONCLUSION: Case-specific anaesthetic plan is necessary before the operation, and it is crucial to maintain good ventilation without interfering with the surgical procedures during the operation.

Effect of patient-controlled epidural analgesia for pain relief after thymectomy in patients with myasthenia gravis.

OBJECTIVE: To evaluate the effect of patient-controlled epidural analgesia (PCEA) with ropivacaine or bupivacaine in relieving pain after thymectomy in patients with myasthenia gravis. METHODS: Twenty adult ASA I-II patients with myasthenia gravis were randomized to receive either 0.125% ropivacaine (Group R, n=10) or 0.125% bupivacaine (Group B, n=10) with a PCEA device after transsternal thymectomy. PCEA (continuous infusion at 1 ml/h, bolus dose of 4 ml and lockout time of 30 min) was implemented via an epidural catheter inserted in the T3-4 intervertebral space. The vital signs and visual analogue scale (VAS), together with cumulative consumption (CC) of ropivacaine or bupivacaine were recorded within 48 h postoperatively. RESULTS: The vital signs, including systolic and diastolic blood pressure, heart rate, SpO2, pH and PaCO2, did not show any significant differences between the 2 groups. The CC of the local anesthetic was significantly higher in group R than that in group B at 24 and 48 h postoperatively, but VAS were not significantly different between the 2 groups which was less than 4 in both groups. CONCLUSIONS: PCEA with low concentration of ropivacaine or bupivacaine may provide effective and safe analgesia after transsternal thymectomy.