Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

OBJECTIVE: To investigate the effects of gene of phosphate and tension homology (PTEN)-induced putative kinase 1 (PINK1)/Parkin pathway on hippocampal mitophagy and cognitive function in mice with sepsis-associated encephalopathy (SAE) and its possible mechanism. METHODS: A total of 80 male C57BL/6J mice were randomly divided into Sham group, cecal ligation puncture (CLP) group, PINK1 plasmid transfection pretreatment groups (p-PINK1+Sham group, p-PINK1+CLP group), empty vector plasmid transfection control group (p-vector+CLP group), with 16 mice in each group. The mice in CLP groups were treated with CLP to reproduce SAE models. The mice in the Sham groups were performed laparotomy only. Animals in the p-PINK1+Sham and p-PINK1+CLP groups were transfected with PINK1 plasmid through the lateral ventricle at 24 hours before surgery, while mice in the p-vector+CLP group were transfected with the empty plasmid. Morris water maze experiment was performed 7 days after CLP. The hippocampal tissues were collected, the pathological changes were observed under a light microscope after hematoxylin-eosin (HE) staining, and the mitochondrial autophagy was observed under a transmission electron microscopy after uranyl acetate and lead citrate staining. The expressions of PINK1, Parkin, Beclin1, interleukins (IL-6, IL-1β) and microtubule-associated protein 1 light chain 3 (LC3) were detected by Western blotting. RESULTS: Compared with the Sham group, CLP group mice in Morris water maze experiment had longer escape latency, shorter target quadrant residence time, and fewer times of crossing the platform at 1-4 days. Under the light microscope, the hippocampal structure of the mouse was injured, the neuronal cells were arranged in disorder, and the nuclei were pyknotic. Under the electron microscope, the mitochondria appeared swollen, round, and wrapped by bilayer or multilayer membrane structures. Compared with the Sham group, CLP group had higher expressions of PINK1, Parkin, Beclin1, LC3II/LC3I ratio, IL-6 and IL-1β in hippocampus, indicating that sepsis induced by CLP could activated inflammatory response and caused PINK1/Parkin-mediated mitophagy. Compared with the CLP group, p-PINK1+CLP group had shorter escape latencies, spent more time in the target quadrant and had more number of crossings in the target quadrant at 1-4 days. Under the light microscope, the hippocampal structures of mice was destroyed, the neurons were arranged disorderly, and the nuclei were pyknotic. Under transmission electron microscope, swollen and rounded mitochondria and mitochondrial structure wrapped by double membrane or multilayer membrane structure were observed. Compared with the CLP group, the levels of PINK1, Parkin, Beclin1 and LC3II/LC3 ratio in the p-PINK1+CLP group were significantly increased [PINK1 protein (PINK1/β-actin): 1.95±0.17 vs. 1.74±0.15, Parkin protein (Parkin/β-actin): 2.06±0.11 vs. 1.78±0.12, Beclin1 protein (Beclin1/β-actin): 2.11±0.12 vs. 1.67±0.10, LC3II/LC3I ratio: 3.63±0.12 vs. 2.27±0.10, all P < 0.05], while the levels of IL-6 and IL-1β were significantly decreased [IL-6 protein (IL-6/β-actin): 1.69±0.09 vs. 2.00±0.11, IL-1β protein (IL-1β/β-actin): 1.11±0.12 vs. 1.65±0.12, both P < 0.05], suggesting that overexpression of PINK1 protein could further activate mitophagy and reduce the inflammatory response caused by sepsis. There was no statistically significant difference in the above pathological changes and related indicators between Sham group and p-PINK1+Sham group, CLP group and p-vector+CLP group. CONCLUSIONS PINK1 overexpression can further activate CLP-induced mitophagy by upregulating Parkin, thereby inhibiting inflammation response and alleviate cognitive function impairment in SAE mice.
Male ; Animals ; Mice ; Mice, Inbred C57BL ; Sepsis-Associated Encephalopathy ; Phosphates ; Actins ; Beclin-1 ; Interleukin-6 ; Autophagy ; Ubiquitin-Protein Ligases ; Cognitive Dysfunction ; Sepsis ; Mitochondria ; Protein Kinases

Objective:To explore the clinical effect of different flow rates of transnasal humidified rapid-insufflation ventilatory exchange (Thrive) on hypoxic events during painless gastroscopy.Methods:Patients who underwent painless gastroscopy in Nanjing First Hospital from April to July 2020 were randomly selected by random number table method and assigned to Thrive groups of 30 L/min ( n=52), 50 L/min ( n=55) and 70 L/min ( n=54). The incidences of different degree of hypoxic events (including subclinical respiratory depression, hypoxia and severe hypoxia) and adverse events related to Thrive were recorded. Results:The total incidence of hypoxic events in the 70 L/min group was 0 (0/54), which was significantly lower than that in the 30 L/min group (21.3%, 11/52, χ2=12.75, P<0.001) and 50 L/min group (12.7%, 7/55, P=0.007). There were no significant differences in subclinical respiratory depression [13.5% (7/52) VS 5.5% (3/55), χ2=1.19, P=0.194] or hypoxia [7.7% (4/52) VS 7.3% (4/55), P=0.610] between 30 L/min group and 50 L/min group. No severe hypoxia occurred in any group. The oxygenation of patients with hypoxemia in 30 L/min and 50 L/min groups was improved (SpO 2>95%) after opening the airway by mandibular support. In addition, there were no significant differences in the incidence of adverse events except hypoxemia among the three groups ( P>0.05). Conclusion:The flow rates of Thrive of 30 L/min, 50 L/min, and 70 L/min can prevent the occurrence of severe hypoxia during painless gastroscopy, and the flow rate of 70 L/min can further reduce the incidence of subclinical respiratory depression.

Objective:To compare the efficacy of different volume of ropivacaine for subomohyiod anterior suprascapular nerve block (aSSNB) in the patients undergoing arthroscopic shoulder surgery with general anesthesia.Methods:One hundred and thirty-five patients of either sex, aged 18-64 yr, with body mass index of 18-30 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, scheduled for elective arthroscopic shoulder surgery, were divided into 3 groups ( n=45 each) using a random number table method: 0.5% ropivacaine 5 ml group (L group), 10 ml group (M group), and 15 ml group (H group). Before induction, aSSNB was performed with 0.5% ropivacaine 5, 10 and 15 ml in L, M and H groups, respectively.Diaphragmatic excursion, occurrence and degree of diaphragmatic paralysis, decrease in SpO 2, dyspnea and Horner syndrome were recorded at 30 min after injection.The intraoperative consumption of remifentanil and cardiovascular events were recorded.The extubation time, length of post-anesthesia care unit stay, and duration of sensory block were recorded.Quality of Recovery-15 scale score and score for patient′s satisfaction with analgesia were recorded.The first pressing time of analgesic pump, effective pressing frequency of analgesic pump, requirement for rescue analgesia, nausea, vomiting and nerve block-related complications within 24 h after surgery were recorded. Results:Compared with group L, the incidence of diaphragmatic paralysis was significantly increased, the degree of diaphragmatic paralysis was aggravated, the first pressing time of analgesic pump and duration of sensory block were prolonged, the effective pressing times of analgesic pump was reduced, and the requirement for rescue analgesia was decreased in M and H groups, and the decrease in SpO 2 was significantly increased, and the introperative consumption of remifentanil was decreased in group H ( P<0.05). Compared with group M, the decrease in SpO 2 and incidence of diaphragmatic paralysis were significantly increased, the degree of diaphragmatic paralysis was aggravated, the first pressing time of analgesic pump and duration of sensory block were prolonged ( P<0.05), and no significant change was found in the introperative consumption of remifentanil, the effective pressing times of analgesic pump or requirement for rescue analgesia in group H ( P>0.05). There was no significant difference in the incidence of cardiovascular events, score for patient′s satisfaction with analgesia, incidence of dyspnea and extubation time, length of post-anesthesia care unit stay, Quality of Recovery-15 sacle score, and the incidence of nausea and vomiting among three groups ( P>0.05). There were no Horner syndrome and nerve block-related complications in the three groups. Conclusions:Subomohyoid aSSNB with 0.5% ropivacaine hydrochloride 10 ml provides optimal efficacy when used for subomohyiod anterior suprascapular nerve block in patients undergoing arthroscopic shoulder surgery with general anesthesia.

Sepsis associated encephalopathy (SAE) is a severe disease secondary to sepsis, which is associated with increased mortality and causes long-term cognitive deficits in survivors. Recently, an increasing body of evidence has shown that gut microbiota is closely related to the central nervous system, and could influence brain function via microbiota-gut-brain axis. Therefore, in the occurrence and development of SAE, cholinergic anti-inflammatory pathway is one of the mechanisms by which gut microbiota could improve cognitive function. Efferocytosis, a process of eliminating apoptotic cells in the body, has anti-inflammatory effects and provides organ protection in sepsis. On the other hand, it could be enhanced by some metabolites of gut microbiota, making it another potential mechanism for gut microbiota regulating SAE. This review summarizes the mutual regulation of gut microbiota, efferocytosis and SAE, to explore potential mechanisms and therapeutic targets of SAE.

Objective:To evaluate the efficacy of subomohyoid anterior suprascapular nerve block (SSNB) in the patients undergoing arthroscopic shoulder surgery with general anesthesia.Methods:Sixty patients of either sex, aged 18-64 yr, with body mass index of 18-30 kg/m 2, of American Society of Anesthesiologists physical status Ⅰor Ⅱ, scheduled for elective arthroscopic shoulder surgery, were divided into 2 groups ( n=30 each) using a random number table method: SSNB group (S group) and interscalene brachial plexus block group (I group). Before induction, 0.375% ropivacaine hydrochloride 15 ml was injected between C 5-C 6 nerve roots in group I and around the anterior suprascapular nerve in group S under ultrasound guidance.Diaphragmatic excursion, occurrence and degree of diaphragmatic paralysis, decrease in SpO 2, dyspnea, Horner syndrome and sensory block in the C 5-T 1 dermatomes were assessed at 30 min after injection.The intraoperative consumption of remifentanil, extubation time, and length of post-anesthesia care unit stay were recorded.Quality of Recovery-15 score for patient′s satisfaction with analgesia, effective pressing frequency of analgesic pump, requirement for rescue analgesia, nausea and vomiting and nerve block-related complications within 24 h after surgery were recorded. Results:Compared with group I, the incidence of diaphragmatic paralysis was significantly decreased, the degree of diaphragmatic paralysis was reduced, diaphragmatic excursion was increased, the amplitude of decrease in SpO 2 was reduced, the incidence of dyspnea and Horner syndrome was decreased, extubation time was shortened ( P<0.05), and no significant change was found in the incidence of sensory block in the C 5-T 1 dermatomes, intraoperative consumption of remifentanil, effective pressing frequency of analgesic pump, requirement for rescue analgesia, score for patient′s satisfaction with analgesia, incidence of nausea and vomiting, length of post-anesthesia care unit stay, or Quality of Recovery-15 score in group S ( P>0.05). Conclusions:The subomohyoid anterior SSNB not only provides reliable perioperative analgesia, but also reduces the risk of diaphragmatic paralysis when used in the patients undergoing arthroscopic shoulder surgery with general anesthesia.

Objective:To analyze the characteristics of sleep disordered breathing (SDB) in children with allergic rhinitis (AR), and improve the diagnosis and treatment at AR combined with obstructive sleep apnea (OSA).Methods:The clinical data of 120 patients with AR and OSA (AR and OSA group) admitted to the respiratory department at Shenzhen Children′s Hospital from May 2019 to December 2020 were retrospectively analyzed.A total of 120 children diagnosed with OSA and excluded AR during the same period were selected as control group.The SDB day and night symptoms, sleep structure characteristics and sleep breathing events were compared between two groups.Results:The average course of disease in children with AR and OSA was significantly longer than that in control group ( P=0.030). The main manifestations of children in AR and OSA group were mouth breathing (100.0%), snoring (99.2%), nasal obstruction (88.5%), and restless sleep (68.0%). There was no significant difference in sleep structure between two groups ( P>0.05), but the sleep efficiency of AR and OSA group was significantly lower than that of control group ( P=0.028). The respiratory events apnea hypopnea index, obstructive apnea index, obstructive apnea hypopnea index, hypopnea index and oxygen desaturation index of each sleep period in AR and OSA group were significantly higher than those in control group ( P<0.05). Among the children in AR and OSA group, moderate and severe OSA were the main manifestations, and the difference between two groups was statistically significant ( P<0.001). Conclusion:The combination of AR delayed the course of OSA in children.The main characteristics of sleep disordered breathing in children with AR are mouth opening, restless sleep, snoring and nasal obstruction.The sleep efficiency is decreased.Obstructive hypopnea and apnea are the most common respiratory events, and oxygen deficiency often occurs in rapid eye movement phase.Children with AR are more likely to have moderate or severe obstructive sleep apnea.

Objective:To compare the effects of five different types of videolaryngoscopes in patients with a simulated difficult airway.Methods:575 patients who needed endotracheal intubation in Nanjing Hospital Affiliated to Nanjing Medical University from May 2021 to September 2021 were randomly divided into 5 groups [UE videolaryngoscope group (U group), GlideScope videolaryngoscope group (G group), C-MAC videolaryngoscope group (C group), Airtraq videolaryngoscope group (A group) and A. P.advance videolaryngoscope group (AP group)], with 115 patients in each group. They all wore cervical collar to simulate difficult airway. The main observation index was the success rate of first endotracheal intubation. Secondary observation indicators included overall success rate, laryngoscope exposure field, intubation time, operator′s subjective score, cause of failure, adverse events, and complications of intubation.Results:The patients′ mouth opening degree was reduced from (46±6)mm to (24±4)mm ( P<0.05) after wearing the cervical collar; The success rate of the first endotracheal intubation were 96%(UE), 92%(C-MAC), 86%(GlideScope), 85%(Airtraq), and 60%(AP.Advance) respectively, with statistically significant difference ( P<0.05); Compared with AP group and G group, the incidence of soft tissue injury or bleeding in U group and C group were lower ( P<0.05); There were significant difference in the overall success rate of videolaryngoscopes, laryngoscope visual field exposure, intubation time, the subjective score of the operator and adverse events ( P<0.05); There was no significant difference in the complications of intubation among the groups ( P>0.05). Conclusions:Among 575 patients with a simulated difficult airway with limited neck mobility and limited mouth opening, there were significant differences in the use of five videolaryngoscopes. Among them, UE video laryngoscope had the highest first intubation success rate and lowest tissue trauma rate, C-MAC video laryngoscope, GlideScope video laryngoscope and Airtraq video laryngoscope followed in performance, while A. P.Advance video laryngoscope performed the worst.

Objective:To compare the efficacy of pericapsular nerve group (PENG) block combined with lateral femoral cutaneous nerve (LFCN) block versus fascia iliaca compartment block (FICB) in elderly patients undergoing total hip arthroplasty under general anesthesia.Methods:Fifty-eight patients of both sexes, aged 65-85 yr, with body mass index of 18-30 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ-Ⅲ, scheduled for elective direct anterior approach to total hip arthroplasty, were divided into 2 groups ( n=29 each) using a random number table method: PENG block plus LFCN block group (PL group) and FICB group (F group). In group PL, the mixture (20 ml) of 0.375% ropivacaine hydrochloride and dexamethasone 3.3 mg was injected around the nerve innervating the hip joint capsule under ultrasound guidance.In group F, the mixture (30 ml) of 0.375% ropivacaine hydrochloride and dexamethasone 5 mg was injected around the nerve innervating the fascia iliaca compartment under ultrasound guidance.All the patients received patient-controlled intravenous analgesia with oxycodone after surgery.When visual analogue scale scores≥4 points, oxycodone 1 mg was intravenously injected as rescue analgesic.The intraoperative consumption of remifentanil was recorded.First time to ambulation, discharge destination, length of hospital stay, and effective pressing times of analgesic pump, requirement for rescue analgesia and the incidence of quadriceps weakness, nausea and vomiting and nerve block related complications within 48 h after surgery were recorded. Results:Compared with F group, intraoperative consumption of remifentanil was significantly decreased, effective pressing times of analgesic pump and incidence of quadriceps weakness were decreased, first time to ambulation and length of hospital stay were shortened, and first discharge destination was prolonged ( P<0.05), and no significant change was found in the requirement for rescue analgesia and the incidence of nausea ( P>0.05) in group PL. Conclusion:PENG block combined with LFCN block can reduce intraoperative consumption of opioids, be helpful for inhibiting postoperative pain sensitivity, and improve early recovery than FICB when used for total hip arthroplasty under general anesthesia.

Objective:To evaluate the relationship between milk fat globular epidermal growth factor Ⅷ (MFG-E8)-mediated efferocytosis and sepsis-associated encephalopathy (SAE) in mice.Methods:Forty clean-grade healthy male C57BL/6 mice, aged 2-3 months, weighing 18-22 g, were divided into 4 groups ( n=10 each) using a random number table method: sham operation group (group Sham), cecal ligation and perforation (CLP) group (group CLP), sham operation+ phosphate buffer solution (PBS) group (group Sham+ PBS) and CLP+ recombinant mouse MFG-E8 group (group CLP+ rmMFG-E8). SAE was induced by CLP in anesthetized mice.PBS 1 μl and rmMFG-E8 1 μg were injected into the lateral cerebral ventricle in Sham+ PBS and CLP+ rmMFG-E8 groups after operation for 5 consecutive days.Novel object recognition test was performed at 6 days after operation, and the contextual fear conditioning test was performed at 7 and 8 days after operation.The percentage of time spent exploring a novel object, discrimination index and percentage of freezing time induced by condition were calculated.The animals were sacrificed after the end of behavioral tests, and the hippocampus was extracted for determination of the expression of MFG-E8 and GTP-Rac1 (by Western blot), the mRNA expression levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-1β (using real-time reverse transcription-polymerase chain reaction) and the apoptosis rate in hippocampus (by TUNEL). Results:Compared with group Sham, the percentage of time spent exploring a novel object, discrimination index and percentage of freezing time were significantly decreased, hippocamcal MFG-E8 expression was down-regulated, GTP-Rac1 expression was up-regulated, mRNA expression of IL-6, TNF-α and IL-1β was up-regulated, and apoptosis rate was increased in group CLP ( P<0.05). Compared with group CLP, the percentage of time spent exploring a novel object and discrimination index were significantly increased, freezing time was prolonged, hippocamcal MFG-E8 and GTP-Rac1 expression was up-regulated, mRNA expression of IL-6, TNF-α and IL-1β was down-regulated, and apoptosis rate was decreased in group CLP+ rmMFG-E8 ( P<0.05). Conclusion:The reduction of hippocampal MFG-E8-mediated efferocytosis may be involved in the pathophysiological mechanism of SAE in mice.