TRIM45 aggravates microglia pyroptosis via Atg5/NLRP3 axis in septic encephalopathy.

BACKGROUND: Neuroinflammation mediated by microglial pyroptosis is an important pathogenic mechanism of septic encephalopathy (SAE). It has been reported that TRIM45 is associated with tumours and inflammatory diseases. However, the role of TRIM45 in SAE and the relationship between TRIM45 and microglial pyroptosis are unknown. In this study, we found that TRIM45 played an important role in regulating microglial pyroptosis and the molecular mechanism. METHODS: SAE was induced by intraperitoneal injection of LPS in WT and AAV-shTRIM45 mice. BV2 cells were treated with LPS/ATP in vitro. Cognitive function was assessed by the Morris water maze. Nissl staining was used to evaluate histological and structural lesions. ELISA was used to dectect neuroinflammation. qPCR was used to detect the mRNA levels of inflammatory cytokines, NLRP3, and autophagy genes. Western blotting and immunofluorescence analysis were used to analyse the expression of the proteins. Changes in reactive oxygen species (ROS) in cells were observed by flow cytometry. Changes in mitochondrial membrane potential in BV2 cells were detected by JC-1 staining. Peripheral blood mononuclear cells were extracted from blood by density gradient centrifugation and then used for qPCR, western blotting and flow detection. To further explore the mechanism, we used the overexpression plasmids TRIM45 and Atg5 as well as siRNA-TRIM45 and siRNA-Atg5 to analyse the downstream pathway of NLRP3. The protein and mRNA levels of TRIM45 in peripheral blood mononuclear cells from sepsis patients were examined. RESULTS: Knocking down TRIM45 protected against neuronal damage and cognitive impairment in septic mice. TRIM45 knockdown inhibited microglial pyroptosis and the secretion of inflammatory cytokines in vivo and in vitro, which was mediated by NLRP3/Gsdmd-N activation. Overexpression of TRIM45 could activate NLRP3 and downstream proteins. Further examination showed that TRIM45 regulated the activation of NLRP3 by altering Atg5 and regulating autophagic flux. It was also found that overexpression and knockdown of TRIM45 affected the changes in ROS and mitochondrial membrane potential. Thus, knocking down TRIM45 could reduce microglial pyroptosis, the secretion of proinflammatory cytokines, and neuronal damage and improve cognitive function. In addition, the level of TRIM45 protein in septic patients was increased. There was a positive linear correlation between APACHE II score and TRIM45, between SOFA score and TRIM45. Compared to group GCS > 9, level of TRIM45 were increased in group GCS ≤ 8. CONCLUSION: TRIM45 plays a key role in neuroinflammation caused by LPS, and the mechanism may involve TRIM45-mediated exacerbation of microglial pyroptosis via the Atg5/NLRP3 axis.

Analysis of preoperative sleep quality and related influencing factors in cancer patients.

PURPOSE: The sleep disturbance in cancer patients is more prevalent, and it significantly affects these patients' recovery after the operation. However, the clinical characteristics regarding sleep quality are scarce. This study aimed to evaluate the quality of preoperative sleep quality and its risk factors in different cancer patients requiring elective surgery. PATIENTS AND METHODS: Cancer patients who were scheduled for elective surgery were selected. The demographic data, basic preoperative diseases, and factors related to the preoperative hospital environment were also recorded. Self-made questionnaires (such as gender, age, and personal history), and the Anxiety Self-Assessment Scale were used to assess the patient's underlying condition. The modified Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the preoperative sleep status. RESULTS: A total of 297 patients completed the investigation. The incidence of preoperative sleep disturbance in cancer patients was 47.8%. Multiple logistic regression showed that patients with PSQI ≥ 7 were associated with females (odds ratios [95% confidence intervals]): 1.815 [1.031-3.193], p = 0.039), and the ward space was confined (3.127 [1.016-9.625], p = 0.047), which increased the possibility of sleep disturbance in cancer patients. Meanwhile, increased anxiety levels (1.323 [1.261-1.439], p < 0.001) significantly increased the likelihood of sleep disorders in cancer patients. CONCLUSION: 47.8% of sleep disturbance in cancer patients before surgery. Female patients, preoperative anxiety, and confined ward environment were independent risk factors of subjective sleep disturbance.

JNK-IN-8, a c-Jun N-terminal kinase inhibitor, improves functional recovery through suppressing neuroinflammation in ischemic stroke.

C-Jun N-terminal kinase (JNK) is a pivotal MAPK (mitogen-activated protein kinase), which activated by ischemia brain injury and plays a fairly crucial function in cerebral ischemic injury. Emerging studies demonstrated that JNK-IN-8 (a JNK inhibitor with high specificity) regulates traumatic brain injury through controlling neuronal apoptosis and inflammation. However, the function of JNK-IN-8 in ischemic stroke and the mechanisms underlying of JNK-IN-8 about neuroprotection are not well understood. In this work, male rats were treated with JNK-IN-8 after transient middle cerebral artery occlusion, and then the modified improved neurological function score (mNSS), the foot-fault test (FFT), interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α) levels were assessed. We found that JNK-IN-8-treated rats with MCAO exerted an observable melioration in space learning as tested by the improved mNSS, and showed sensorimotor functional recovery as measured by the FFT. JNK-IN-8 also played anti-inflammatory roles as indicated through decreased activation of microglia and decreased IL-6, IL-1ß, and TNF-α expression. Furthermore, JNK-IN-8 suppressed the activation of JNK and nuclear factor-κB (NF-κB) signaling as indicated by the decreased level of phosphorylated-JNK and p65. All data demonstrate that JNK-IN-8 inhibits neuroinflammation and improved neurological function by inhibiting JNK/NF-κB and is a promising agent for the prevention of ischemic brain injury.

Electroacupuncture Attenuates CFA-Induced Inflammatory Pain by Regulating CaMKII.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a multifunctional serine/threonine kinase that is ubiquitously distributed in the central and peripheral nervous systems. Moreover, its phosphorylated protein (P-CaMKII) is involved in memory, mood, and pain regulation in the anterior cingulate cortex (ACC). Electroacupuncture (EA) is a traditional Chinese therapeutic technique that can effectively treat chronic inflammatory pain. However, the CaMKII-GluA1 role in EA analgesia in the ACC remains unclear. This study investigated the role of P-CaMKII and P-GluA1 in a mouse model of inflammatory pain induced by complete Freund's adjuvant (CFA). There were increased P-CaMKII and P-GluA1 levels in the ACC. We found that intracerebroventricular injection of KN93, a CaMKII inhibitor, as well as EA stimulation, attenuated complete Freund's adjuvant-induced pain behavior. Further, EA increased pCaMKII-PICK1 complex (abbreviated as C-P complex) levels. Our findings demonstrate that EA inhibits inflammatory pain by inhibiting CaMKII-GluA1 phosphorylation. P-CaMKII is involved in EA analgesia as the pCaMKII-PICK1 complex.

PICK1 Deficiency Induces Autophagy Dysfunction via Lysosomal Impairment and Amplifies Sepsis-Induced Acute Lung Injury.

Sepsis is a systemic inflammatory reaction caused by infection. Multiple organ failure ultimately leads to high morbidity and mortality. Unfortunately, therapies against these responses have been unsuccessful due to the insufficient underlying pathophysiological evidence. Protein interacting with C-kinase 1 (PICK1) has received considerable attention because of its important physiological functions in many tissues. However, its role in sepsis-induced acute lung injury (ALI) is unclear. In this study, we used cecal ligation and puncture (CLP) to establish a septic model and found that decreased microtubule-associated protein-1light chain 3 (LC3)-II/LC3-I in PICK1-/- septic mice was caused by autophagy dysfunction. Consistently, the transmission electron microscopy (TEM) of bone marrow-derived macrophages (BMDMs) from PICK1-/- mice showed the accumulation of autophagosomes as well. However, more serious damage was caused by PICK1 deficiency indicating that the disrupted autophagic flux was harmful to sepsis-induced ALI. We also observed that it was the impaired lysosomal function that mediated autophagic flux blockade, and the autophagy progress was relevant to PI3K-Akt-mTOR pathway. These findings will aid in the potential development of PICK1 with novel evidence of autophagy in sepsis treatment and prevention.

The Effect of Transcutaneous Electrical Acupoint Stimulation on Inflammatory Response in Patients Undergoing Limb Ischemia-Reperfusion.

Reperfusion after tourniquet use can induce inflammation and cause remote organ injury. We evaluated the therapeutic effect of transcutaneous electrical acupoint stimulation (TEAS) on inflammatory mediators and lung function in patients receiving lower limb tourniquets. Forty patients undergoing unilateral lower extremity surgery with tourniquet were randomly assigned to two groups: the TEAS group and ischemia-reperfusion (I/R) group. The C-C motif chemokine ligand 2 (CCL2), C-X-C motif chemokine ligand 8 (CXCL8), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and arterial blood gas analysis were measured preoperatively and 6 h after tourniquet removal. The levels of CXCL8, IL-1, IL-6, TNF-α, and CCL2 were significantly increased compared to baseline values in both groups, but the increase was significantly smaller in the TEAS group. In the TEAS group, the partial pressure of oxygen and arterial-alveolar oxygen tension ratio were significantly decreased, and the alveolar-arterial oxygen tension difference and respiratory index were significantly increased, compared to those in the I/R group at 6 h after reperfusion. In conclusion, TEAS diminished the upregulation of proinflammatory factors in response to lower limb ischemia-reperfusion and improved pulmonary gas exchange.

Prevention of propofol injection-related pain using pretreatment transcutaneous electrical acupoint stimulation

Background/aim: This study aimed to study the effect of pretreatment transcutaneous electrical acupoint stimulation (TEAS) in preventing propofol injection-related pain. Materials and methods: A total of 360 patients who were to undergo elective hysteroscopy surgery were randomly divided into the following three groups of 120 patients each: control (Group C), sham TEAS (Group F), and TEAS (Group T). Patients in Group C did not undergo any treatment before surgery; 30 min before the induction of anesthesia, patients in Groups F and T underwent electrical stimulation of the bilateral LI4-PC6 acupoint. Patients in Group F were subjected to 'feeling flow', while those in Group T were subjected to 'tolerance flow.' The stimulation frequency was 2/100 Hz and the duration of stimulation was 30 min. After the induction of anesthesia, propofol injection-related pain scores, hemodynamic parameters, and adverse reactions were recorded. Results: Of the 360 patients, 324 completed the study. There were significant differences among the groups in terms of the incidence of moderate-to-severe pain. In terms of the four-point scaling method, the end of the radial vein, the cubital vein, and the 'back of the hand' vein differed significantly among the three groups (P = 0.05). Finally, using a numerical rating scale, a significant difference was observed among the three groups in terms of the pain scores in the different veins. Conclusions: Pretreatment TEAS effectively reduces the incidence and severity of propofol injection-related pain, the incidence of postoperative nausea and vomiting, and patient postoperative pain scores.

Flurbiprofen Axetil Enhances Analgesic Effects of Sufentanil and Attenuates Postoperative Emergence Agitation and Systemic Proinflammation in Patients Undergoing Tangential Excision Surgery.

OBJECTIVE: Our present study tested whether flurbiprofen axetil could reduce perioperative sufentanil consumption and provide postoperative analgesia with decrease in emergency agitation and systemic proinflammatory cytokines release. METHODS: Ninety patients undergoing tangential excision surgery were randomly assigned to three groups: (1) preoperative dose of 100 mg flurbiprofen axetil and a postoperative dose of 2 µg/kg sufentanil and 10 mL placebo by patient-controlled analgesia (PCA) pump, (2) preoperative dose of 100 mg flurbiprofen axetil and a postoperative dose of 2 µg/kg sufentanil and 100 mg flurbiprofen axetil by PCA pump, and (3) 10 mL placebo and a postoperative dose of 2 µg/kg sufentanil and 10 mL placebo by PCA pump. RESULTS: Preoperative administration of flurbiprofen axetil decreased postoperative tramadol consumption and the visual analog scale at 4, 6, 12, and 24 h after surgery, which were further decreased by postoperative administration of flurbiprofen axetil. Furthermore, flurbiprofen axetil attenuated emergency agitation score and Ramsay score at 0, 5, and 10 min after extubation and reduced the TNF-α and interleukin- (IL-) 6 levels at 24 and 48 h after the operation. CONCLUSION: Flurbiprofen axetil enhances analgesic effects of sufentanil and attenuates emergence agitation and systemic proinflammation in patients undergoing tangential excision surgery.

Risk factors for postoperative delirium in elderly patients undergoing heart valve surgery with cardiopulmonary bypass.

BACKGROUND: The aim of this study was to identify the risk factors for postoperative delirium (POD) in elderly patients undergoing heart valve surgery with cardiopulmonary bypass (CPB). METHODS: Elderly patients undergoing elective heart valve surgery with CPB in The First Affiliated Hospital of Wenzhou Medical University between March 2022 and March 2023 were selected for this investigation. They were divided into a POD group and a non-POD group. Their baseline information was collected and recorded, and the patients were subjected to neurocognitive function assessment using the Mini-Mental State Examination and the Montreal Cognitive Assessment scales before surgery. We also recorded their intraoperative indicators such as duration of surgery, duration of CPB, duration of aortic cross-clamp, blood transfusion, and postoperative indicators such as duration of mechanical ventilation, postoperative 24-hour drainage volume, and pain score. Regional cerebral oxygen saturation was monitored intraoperatively by near-infrared spectroscopy based INVOS5100C Regional Oximeter. Patients were assessed for the occurrence of POD using Confusion Assessment Method for the Intensive Care Unit, and logistic regression analysis of risk factors for POD was performed. RESULTS: The study finally included 132 patients, with 47 patients in the POD group and 85 ones in the non-POD group. There were no significant differences in baseline information and preoperative indicators between the two groups. However, marked differences were identified in duration of surgery, duration of CPB, duration of aortic cross-clamp, duration of postoperative mechanical ventilation, postoperative length of stay in cardiac intensive care unit, postoperative length of hospital stay, intraoperative blood transfusion, postoperative pain score, and postoperative 24-hour drainage volume between the two groups (p < 0.05). Additionally, the two groups had significant differences in rScO2 at each intraoperative time point and in the difference of rScO2 from baseline at each intraoperative time point (p < 0.05). Multivariate logistic regression analysis showed that duration of surgery > 285 min (OR, 1.021 [95% CI, 1.008-1.035]; p = 0.002), duration of postoperative mechanical ventilation > 23.5 h (OR, 6.210 [95% CI, 1.619-23.815]; p = 0.008), and postoperative CCU stay > 3.5 d (OR, 3.927 [95% CI, 1.046-14.735]; p = 0.043) were independent risk factors of the occurrence of POD while change of rScO2 at T1>50.5 (OR, 0.832 [95% CI 0.736-0.941]; p = 0.003) was a protective factor for POD. CONCLUSION: Duration of surgery duration of postoperative mechanical ventilation and postoperative CCU stay are risk factors for POD while change of rScO2 at T1 is a protective factor for POD in elderly patients undergoing heart valve surgery with CPB.

[Local adenosine A1 receptors of baihui acupoint mediate cerebral ischemia tolerance induced by Electroacupuncture].

OBJECTIVE: To investigate whether local A1R of Baihui acupoint mediate cerebral ischemia tolerance induced by electro-acupuncture (EA). METHODS: Sixty SD rats were randomly divided into five groups, i.e., the sham-operation (S) group, the model group (M), the electroacupuncture (E) group, the CCPA group and the DMSO group. The focal cerebral ischemia/reperfusion model was established by middle cerebral artery occlusion (MCAO) in rats. Rats in the E group were received EA pretreatment baihui acupoint at 2 h before established MCAO. The rats in DMSO group and the CCPA group were injected with DMSO (20 µl) and CCPA (0.1 mmol/L) 20 µl into Baihui, respectively, at 2 h before established MCAO. After 24 h reperfusion, the rats' behavior, cerebral infarct volume, the cerebral Bcl-2 protein expression were assessed. RESULTS: Compared with M group, the rats' behavior was improved, the cerebral infarct volume was decreased and the Bcl-2 protein expression was up-regulated (P < 0.05) in the E group. Compared with M and DMSO group, the rats' behavior was improved, the cerebral infarct volume was decreased and the Bcl-2 protein expression was up-regulated (P < 0.05) in the CCPA group. There were no statistical differences between CCPA and E group. CONCLUSIONS: EA induced cerebral ischemia tolerance. Local A1R of Baihui acupoint possible mediate cerebral ischemia tolerance induced by Electroacupuncture.

[Effect of transcutaneous acupoint electrical stimulation on stress in brain surgery with propofol target controlled infusion general anesthesia].

OBJECTIVE: To study the effect of transcutaneous acupoint electrical stimulation (TAES) on stress who received propofol target controlled infusion (TCI) general anesthesia in brain surgery. METHODS: Totally 40 neurosurgical patients of I-II grade (ASA grading) in our hospital were randomly divided into the TAES group (T group) and the control group (C group), 20 in each group. All patients received intravenous anesthesia by propofol TCI. The TAES intervention was adopted in those of C group. Electrodes were only applied to corresponding acupoints without electric stimulation. The arterial blood was withdrawn before TAES (T0), before anesthesia (T1), before cutting (T2), at 60 min after encephalic incision (T3), immediately after incisions suture (T4), at about 10 min after removing tracheal catheters (T5) to detect beta-endorphin (beta-EP), cortisol (COR), adrenalin (E), blood sugar (Glu). The heart rate (HR) and mean arterial pressure (MAP) were recorded. The total time of surgery, anesthesia, total infusion amount, blood lost amount, and urine amount were recorded. RESULTS: In both groups, HR, MAP, COR, and E at T2 were lower than at T0 significantly (P < 0.05). beta-EP in group C at T2 was lower than at T0 significantly (P < 0.05). HR, MAP, COR in group C at T3 were higher than at T0 significantly (P < 0.05). HR, MAP, E, and Glu in group C at T4 and T5 were higher than at T0 significantly (P < 0.05). beta-EP in group T at T1 and T3 were higher than at T0 significantly (P < 0.05). HR, COR, E, Glu, and beta-EP in group T at T4 and T5 were higher than at T0 significantly (P < 0.05). Between groups, comparing with the time point T0, the amplitude of variation of MAP, COR, and E at T2 in group C were significantly less (P < 0.05); the amplitude of variation of HR, MAP, and COR at T3 in group C were less significantly, when compared with the time point T0 (P < 0.05); the amplitude of variation of HR, MAP, COR, E, and Glu at T4 and T5 in group C were less significantly, when compared with the time point T0 (P < 0.05). When comparing the two groups, the amplitude of variation of beta-EP at time points of T1, T3, T4, and T5 in group T were larger than at T0 in group C (P < 0.05). CONCLUSION: TAES could reduce stress and stabilize the internal environment when used in brain surgery with propofol TCI general anesthesia.

[The role of adenosine deaminase in the electroacupuncture preconditioning induced rapid tolerance to focal cerebral ischemia].

OBJECTIVE: To observe the electroacupuncture (EA) pretreatment at Baihui (GV20) on the concentration of adenosine deaminase (ADA) and adenosine, and to evaluate its effects on the neurologic function score and the infarction volume after middle cerebral artery occlusion (MCAO) ischemia/reperfusion (I/R), thus exploring its mechanisms for relieving the ischemia/reperfusion injury. METHODS: Totally 54 male SD rats were randomly divided into 3 groups, the sham-EA group, the EA group, and the control group, 18 in each group. Rats in the control group were not intervened after anesthesia. Rats in the EA group were needled at Baihui (GV20) for 30 min. Rats in the sham-EA group received the same procedure as those performed in the EA group without electricity connected. The changes of adenosine and ADA contents were detected at 30, 60, and 120 min after EA respectively. The I/R model was established. Totally 48 male SD rats were randomly divided into 6 groups, i.e., the model group (Group A), the EA group (Group B), the EA +8-Cyclopentyl-1,3-dipropylxanthine (DPCPX) group (Group C), the EA + DMSO group (Group D), the Deoxycoformycin (Deo) group (Group E), and the normal saline group (Group F). Rats in Group B, C, and D received EA for 30 min before modeling. Rats in Group C and D were peritoneally injected with DPCPX (1 mg/kg) and DMSO (1 mL/kg) at 30 min before EA. The neurologic function score was evaluated and the infarct volumes were detected after 24-h reperfusion. RESULTS: Compared with the sham-EA group, there was no statistical difference in the contents of the adenosine or ADA in the control group at each time point (P > 0.05). Compared with the control group at the same time point, the content of ADA significantly decreased at 60 min in the EA group [(315.0 +/- 22.9 U/L), P < 0.05], and restored to the normal level at 120 min after EA. The content of adenosine increased in the EA group at 120 min [(20.4 +/- 2.2) ng/microL, P < 0.05]. Compared with the model group, the neurologic function score decreased (P < 0.05) and the infarct volumes were obviously reduced (P < 0.01) in Group B, D and E. There was no statistical difference in the neurologic function score or the infarct volumes in other groups, when compared with the model group (P > 0.05) CONCLUSION: EA at Baihui (GV20) showed protective effects on the cerebral I/R rats, which might be achieved through lowering the ADA concentration and elevating the adenosine content, and further activating adenosine A1 receptor.

Glycogen synthase kinase-3ß mediates toll-like receptors 4/nuclear factor kappa-B-activated cerebral ischemia-reperfusion injury through regulation of fat mass and obesity-associated protein.

BACKGROUND: Glycogen synthase kinase-3ß (GSK3ß), fat mass and obesity-associated protein (FTO), and toll-like receptors 4 (TLR4) take on critical significance in different biological processes, whereas their interactions remain unclear. The objective was the investigation of the interaction effect in cerebral ischemia-reperfusion (I/R) injury. METHODS: The function of the cerebral cortex in the mouse middle cerebral artery occlusion (MCAO) model (each group n = 6) and P12 cells oxygen-glucose deprivation/reoxygenation (OGD/R) model was analyzed using short hairpin GSK3ß lentivirus and overexpression of FTO lentivirus (in vitro), TLR4 inhibitor (TAK242), and LiCl to regulate GSK3ß, FTO, TLR4 expression, and GSK3ß activity, respectively. RESULTS: After GSK3ß knockdown in the OGD/R model of PC12 cells, the levels of TLR4 and p-p65 were lower than in the control, and the level of FTO was higher than in the control. Knockdown GSK3ß reversed the OGD/R-induced nuclear factor kappa-B transfer to the intranuclear nuclei. As indicated by the result, TLR4 expression was down-regulated by overexpressed FTO, and TLR4 expression was up-regulated notably after inhibition of FTO with the use of R-2HG. After the inhibition of the activity of GSK3ß in vivo, the reduction of FTO in mice suffering from MCAO was reversed. CONCLUSIONS: Our research shows that GSK3ß/FTO/TLR4 pathway contributes to cerebral I/R injury.

Gender differences and risk factors for acute kidney injury following cardiac surgery: A single center retrospective cohort study.

Background: We studied AKI incidence and prognosis in cardiac surgery patients under and over 60 years old. Methods: We studied AKI in patients who underwent cardiac surgery at the First Affiliated Hospital of Wenzhou Medical University between Jan 2020 and Dec 2021, using improved global prognostic criteria for diagnosis. Results: After analyzing 781 patients (402 males, 379 females), AKI incidence after surgery was 30.22 %. Adjusting for propensity scores revealed no significant difference in AKI incidence between young males (24.1 %) and females (19.3 %). However, young females had higher AKI stages. Among older patients, AKI incidence was comparable between males (43.4 %) and females (42.2 %), but females had longer intubation times. Independent risk factors for AKI included age, male gender, and BMI, while intraoperative hemoglobin level was protective. Conclusions: No gender gap in AKI frequency for <60 years old and ≥60 years old post-cardiac surgery, yet women display increased AKI severity and extended intubation duration.

Study on the relationship among typhoon, climate change, and acute Stanford type A aortic dissection in southern of Zhejiang in China.

BACKGROUND: The aim of this study was to investigate the relationship between typhoon, climate change, and acute Stanford type A aortic dissection (TAAD) in southern of Zhejiang Province in China. METHOD: 371 patients with TAAD were admitted to three hospitals (the aortic dissection center) in southern of Zhejiang Province, China from January 2015 to December 2020, and data were retrospectively collected, the data included (1) the number of patients admitted in different months and seasons, (2) daily meteorological data in southern of Zhejiang Province, and (3) typhoon information were retrospectively analyzed. RESULTS: The number of TAAD occurred in winter was the highest and in summer was the lowest. The incidence of TAAD was correlated with minimum temperature, maximum wind speed, mean wind speed, and water vapor pressure (P < 0.05). Maximum wind speed (RR 0.37; 95% CI 0.17 to 0.80, P = 0.01) and water vapor pressure (RR 0.96; 95% CI 0.92 to 1, P = 0.03) were the protective factor. The occurrence incidence of TAAD under the influence of typhoon climate was less than that during the period not affected by typhoon (P < 0.05). CONCLUSION: There was a correlation between typhoon, climate change, and the occurrence of TAAD in southern Zhejiang Province. Wind speed, vapor pressure, and typhoon may be protective factors.

The Effect of Transcutaneous Electrical Acupoint Stimulation on High-Risk Patients with PONV Undergoing Laparoscopic Gynecologic Surgery: A Randomized Controlled Trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) is one of the most common complications after general anesthesia. The traditional comprehensive management of PONV usually uses one or two drugs, but this regimen fails to meet the requirements of the latest version of PONV guidelines. The purpose of this study was to evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on high-risk PONV patients who are undergoing laparoscopic gynecological surgery. METHODS: In total, 162 high-risk PONV patients were randomly divided into an experimental group (n = 81) and a control group (n = 81). Both groups were injected with 4 mg of dexamethasone and 0.25 mg of palonosetron. In the experimental group, Nei-guan (PC6) and He-gu (LI4) were stimulated by a transcutaneous acupoint electrical stimulation instrument (HANS200E) 30 min before the surgery. The control group also received electrodes but no stimulation. Variance analysis and rank sum test were used to compare the differences between the two groups. RESULTS: The results of the incidence of postoperative nausea, vomiting, NRS score, degree of abdominal distension, and time to first flatus in the experimental group were lower than those in the control group. Nursing satisfaction of the experimental group was higher than that of the control group. CONCLUSIONS: The study demonstrates that TEAS combined with dexamethasone and palonosetron can effectively prevent PONV, reduce postoperative abdominal distension and postoperative pain, and shorten the first postoperative flatus time in high-risk patients with PONV. At the same time, it can improve nursing satisfaction.

SILENCING M 6 A READER YTHDC1 REDUCES INFLAMMATORY RESPONSE IN SEPSIS-INDUCED CARDIOMYOPATHY BY INHIBITING SERPINA3N EXPRESSION.

ABSTRACT: Sepsis-induced cardiomyopathy (SIC) is one of the most common complications of infection-induced sepsis. An imbalance in inflammatory mediators is the main factor leading to SIC . N 6 -methyladenosine (m 6 A) is closely related to the occurrence and development of sepsis. N 6 -methyladenosine reader YTH domain containing 1 (YTHDC1) is an m 6 A N 6 -methyladenosine recognition protein. However, the role of YTHDC1 in SIC remains unclear. Herein, we demonstrated that YTHDC1-shRNA inhibits inflammation, reduces inflammatory mediators, and improves cardiac function in a LPS-induced SIC mouse model. Based on the Gene Expression Omnibus database analysis, serine protease inhibitor A3N is a differential gene of SIC. Furthermore, RNA immunoprecipitation indicated that serine protease inhibitor A3N (SERPINA3N) mRNA can bind to YTHDC1, which regulates the expression of SERPINA3N. Serine protease inhibitor A3N-siRNA reduced LPS-induced inflammation of cardiac myocytes. In conclusion, the m 6 A reader YTHDC1 regulates SERPINA3N mRNA expression to mediate the levels of inflammation in SIC. Such findings add to the relationship between m 6 A reader YTHDC1 and SIC, providing a new research avenue for the therapeutic mechanism of SIC.

Transcutaneous electrical acupoint stimulation in adult patients receiving gastrectomy/colorectal resection: A randomized controlled trial.

BACKGROUND: Acupuncture promotes the recovery of gastrointestinal function and provides analgesia after major abdominal surgery. The effects of transcutaneous electrical acupoint stimulation (TEAS) remain unclear. AIM: To explore the potential effects of TEAS on the recovery of gastrointestinal function after gastrectomy and colorectal resection. METHODS: Patients scheduled for gastrectomy or colorectal resection were randomized at a 2:3:3:2 ratio to receive: (1) TEAS at maximum tolerable current for 30 min immediately prior to anesthesia induction and for the entire duration of surgery, plus two 30-min daily sessions for 3 consecutive days after surgery (perioperative TEAS group); (2) Preoperative and intraoperative TEAS only; (3) Preoperative and postoperative TEAS only; or (4) Sham stimulation. The primary outcome was the time from the end of surgery to the first bowel sound. RESULTS: In total, 441 patients were randomized; 405 patients (58.4 ± 10.2 years of age; 247 males) received the planned surgery. The time to the first bowel sounds did not differ among the four groups (P = 0.90; log-rank test). On postoperative day 1, the rest pain scores differed significantly among the four groups (P = 0.04; Kruskal-Wallis test). Post hoc comparison using the Bonferroni test showed lower pain scores in the perioperative TEAS group (1.4 ± 1.2) than in the sham stimulation group (1.7 ± 1.1; P = 0.04). Surgical complications did not differ among the four groups. CONCLUSION: TEAS provided analgesic effects in adult patients undergoing major abdominal surgery, and it can be added to clinical practice as a means of accelerating postoperative rehabilitation of these patients.

Unloading the infarcted heart affect MMPs-TIMPs axis in a rat cardiac heterotopic transplantation model.

Ventricular assist devices may function as a bridge to recovery or heart transplantation, however, little is known about its mechanisms. This study examined the role of matrix metalloproteinases (MMP)-tissue inhibitors of metalloproteinases (TIMP) axis in the process of recovery after unloading in a rat ischemic-induce heart failure (HF) model. Myocardial infarction model was created with the coronary artery ligation. The infarcted rats hearts were unloaded by heterotopic cardiac transplantation (n=14). 2 weeks later, the function of normal and infarcted hearts with or without loading was evaluated by Langendorff perfusion model. The hearts were then harvested and prepared for the study of expression of MMPs and TIMPs. Developed pressure in the unloading group was higher than the loading group (P=0.0074). Unloading increased the ratio of TIMP-1-MMP-1(1.38±0.11 vs. 0.76±0.09, P<0.05), TIMP-2-MMP-2 (1.06±0.10 vs. 0.33±0.07, P<0.01), TIMP-3-MMP-9(1.07±0.08 vs. 0.59±0.06, P<0.05). Although MMP-1, 2, 9 were downregulated (P<0.01, 0.01, 0.05, respectively), TIMP-2 and TIMP-3 upregulated (P<0.01, 0.05, respectively), MMP-7 and TIMP-1 was not affected significantly. The infarcted cardiac function could be improved by unloading. It was attributed to downregulation of MMP-1, 2 and 9, and upregulation of TIMP-2 and -3, and furthermore, the ratio of TIMPs to MMPs was increased, which might be more sensitive than sole MMPs or TIMPs for the judgment of myocardial matrix homeostasis.

Gut Flora Mediates the Rapid Tolerance of Electroacupuncture on Ischemic Stroke by Activating Melatonin Receptor through Regulating Indole-3-Propionic Acid.

Electroacupuncture (EA) is commonly used to treat cerebrovascular diseases. This study aimed to clarify the mechanisms of action of treatments of cerebral ischemic stroke from the perspective of gut microecology. We used a mouse model and cell cultures to investigate the effects of EA on the intestinal microflora in mice models of middle cerebral artery occlusion (MCAO) and the mechanisms underlying the antioxidant activities of metabolites. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota. Metabolomic analysis was performed to characterize the metabolic profile differences between the mice in the EA + MCAO and MCAO groups. Gavaging with feces relieved brain damage in mice that received EA (EA mice) more than in mice that did not (non-EA [NEA] mice). The gut microbial composition and metabolic profiles of the EA and NEA mice were different. In particular, the microbiota from the mice in the EA or EA-FMT groups generated more indole-3-propionic acid (IPA) than the microbiota from the mice in the MCAO or NEA-FMT groups. We confirmed that IPA binds to specific melatonin receptors (MTRs) in target cells and exerts antioxidant effects by adding MTR inhibitors or knocking out the MTR1 gene in vivo and in the oxygen and glucose deprivation/reperfusion models of N2a cell experiments. EA can prevent ischemic stroke by improving the composition of intestinal microbiota in MCAO mice. Moreover, this study reveals a new mechanism of intestinal flora regulation of stroke that differs from inflammation/immunity, namely gut microbiota regulates stroke by affecting IPA levels.