Objective:To explore the effects of phased goal directed fluid therapy (GDFT) during anesthesia surgery on tissue perfusion and cognitive function in patients undergoing radical lung cancer surgery.Methods:A total of 108 lung cancer patients were prospectively selected and randomly divided into a control group and a study group using a random number table method. The control group received classical restrictive liquid therapy, while the study group received staged GDFT. We compared the surgical time, intraoperative blood loss, colloid fluid dosage, crystalloid fluid dosage, total output, and urine volume between two groups of patients; Two groups of patients were compared in terms of oxygenation index (OI), respiratory index (RI), central venous oxygen saturation (ScvO 2), lactate (Lac), central venous arterial carbon dioxide partial pressure difference (Pcv-aCO 2), oxygen supply index (DO 2I), and oxygen uptake rate (O 2ERe) before anesthesia induction (T 0), before single lung ventilation (T 1), 1 hour of single lung ventilation (T 2), immediate resumption of dual lung ventilation (T 3), 30 minutes of dual lung ventilation (T 4), and after surgery (T 5); The Mini Mental State Examination (MMSE) was used to evaluate the cognitive function scores of two groups of patients 1 day before surgery and 1 and 3 days after surgery, while recording the incidence of cognitive dysfunction (POCD) and pulmonary complications (including pulmonary infection, acute lung injury, pulmonary embolism, pulmonary edema, atelectasis, etc.) within 3 days after surgery. Results:The amount of crystal fluid and urine output in the research group was significantly lower than that in the control group, while the amount of colloidal fluid was significantly higher than that in the control group (all P<0.05). The OI of the study group T 1-T 5 was significantly higher than that of the control group, while the RI of T 2-T 5 was significantly lower than that of the control group (all P<0.05). The ScvO 2 of the study group T 1 to T 5 was significantly higher than that of the control group, and the Lac was significantly lower than that of the control group (all P<0.05); The MMSE scores of both groups of patients were significantly lower than those before surgery on day 1 and 3 after surgery, and the MMSE scores of the study group were significantly higher than those of the control group on day 1 and 3 after surgery (all P<0.05). The incidence of POCD within 3 days after surgery in the study group was 16.67%(9/54), lower than 37.04%(20/54) in the control group (χ 2=5.704, P=0.017); The incidence of pulmonary complications in the study group was lower than that in the control group (5.56% vs 22.22%, χ 2=4.955, P=0.026). Conclusions:The application of staged GDFT during anesthesia in patients undergoing radical lung cancer surgery can further improve tissue perfusion, improve microcirculation and oxygen supply-demand balance of systemic organs and tissues, including the brain, alleviate perioperative brain function damage, and reduce the occurrence of postoperative POCD compared to conventional liquid therapy.

Objective:To investigate the impact of a pain management model based on clinical pathway (CP) refinement on postoperative pain relief, recovery, and cognitive function in patients undergoing orthopedic joint surgery.Methods:A total of 150 orthopedic joint surgery patients admitted to Handan Central Hospital from February 2018 to January 2021 were selected. They were randomly divided into an observation group (treated with a pain management model based on CP refinement) and a control group (treated with conventional pain management) using a random number table method, with 75 patients in each group. We compared the differences in pain relief, recovery, cognitive function, and postoperative complication rates between two groups of patients.Results:The Visual Analogue Scale (VAS) scores of the observation group patients at 2, 6, 12, and 24 hours after surgery were lower than those of the control group, and the differences were statistically significant (all P<0.05). 24 hours after surgery, the Japanese Orthopaedic Association (JOA) scores of both groups of patients decreased compared to before treatment, and the angle of straight leg elevation test increased compared to before treatment (all P<0.05). In addition, the JOA scores of the observation group were lower than those of the control group, and the angle of straight leg elevation test was greater than that of the control group, with statistical significance (all P<0.05). 24 hours after surgery, the Mini-mental State Examination (MMSE) scores of both groups of patients increased (all P<0.05), and the MMSE scores of the observation group were higher than those of the control group, with statistical significance (all P<0.05). The incidence of postoperative nausea and vomiting in the observation group was significantly lower than that in the control group, and the difference was statistically significant (all P<0.05). Conclusions:The analgesic model based on CP refined management has improved the postoperative analgesic effect, recovery, and cognitive function of patients undergoing orthopedic joint surgery. It is recommended to promote it clinically.

Objective:To compare the effects of transverse abdominis plane block and incision infiltration anesthesia on the early postoperative recovery in the patients undergoing thoracoscopic lung resection with general anesthesia.Methods:Eighty American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ patients, regardless of gender, aged 50-78 yr, with body mass index of 18-30 kg/m 2, scheduled for elective thoracoscopic lung resection under general anesthesia, were divided into 2 groups ( n=40 each) using a random number table method: incision local infiltration group (group D) and transverse abdominis plane block group (group E). In group E, the patients were changed to the lateral position after completion of anesthesia induction, ultrasound-guided transverse abdominis plane block was performed on the affected side, with 0.25% ropivacaine hydrochloride 30 ml injected. In group D, infiltration anesthesia with 0.25% ropivacaine hydrochloride was performed before incision. Postoperative patient-controlled intravenous analgesia was carried out, and flurbiprofen axetil was intravenously injected for rescue analgesia when the numerical rating scale score at rest >3 or numerical rating scale score≥6 while coughing. Quality of Recovery-15 scale scores were assessed at 1 day before surgery and 24 and 48 h after surgery. Plasma concentrations of interleukin-6 (IL-6) and IL-1β were measured by enzyme-linked immunosorbent assay before incision, at the end of surgery, and at 24 h after surgery. The amount of remifentanil used during surgery, the number of effective pressing times of patient-controlled analgesia within 48 h after surgery, requirement for rescue analgesia, first ambulation time after surgery, time to first flatus, length of hospital stay, and occurrence of nausea and vomiting and pulmonary infection within 48 h after surgery were recorded. Results:Compared with group D, Quality of Recovery-15 scale scores were significantly increased, the amount of remifentanil used during surgery and the number of effective pressing times of patient-controlled analgesia were reduced, the rate of rescue analgesia was decreased, the time to first rescue analgesia was prolonged, and the time to first flatus was shortened in group E ( P<0.05). There were no significant differences in the plasma concentrations of IL-6 and IL-1β at various time points, time to first ambulation after surgery, length of hospital stay, and incidence of nausea and vomiting and pulmonary infection between the two groups ( P>0.05). Conclusions:Compared with incision infiltration anesthesia, transverse abdominis plane block can reduce intraoperative consumption of opioids, alleviate postoperative pain, and promote early postoperative recovery when used for thoracoscopic lung resection under general anesthesia.

Objective To investigate the effect of asiatic acid(AA)on the apoptosis of HT-22 cells induced by sevoflurane(SEVO)by regulating phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)signaling pathway.Methods Different concentrations of AA(0,5,10,15,20,30 μmol/L)were used to treat HT-22 cells induced by sevoflurane for 24 hours,and CCK-8 was used to detect HT-22 cell viability;HT-22 cells were divided into control group,sevoflurane(SEVO)group,AA low concentration(AA-L,10 μmol/L)group,AA medium concentration(AA-M,15 μmol/L)group,AA high concentration(AA-H,20 μmol/L)group,and AA high concentration+PI13K pathway inhibitor LY294002(AA-H+LY294002,20 μmol/L AA+5 μmol/L LY294002)group.Inverted microscopy was applied to observe changes of cell morphology,ELISA was applied to detect the levels of inflammatory factors TNF-α and IL-6,oxidative stress indicators SOD,GSH-Px,and MDA,ROS detection kit was applied to detect ROS levels,TUNEL kit was applied to detect HT-22 apoptosis,JC-1 method was applied to detect mitochondrial membrane potential,ATP content detection kit was applied to detect ATP content,and Western blot was applied to detect the expressions of Bcl-2,Bax,Caspase-3,p-PI3K,PI3K,p-AKT,and AKT proteins.Results Compared with 0 μmol/L,the activity of HT-22 cells treated with 5-30 μmol/L AA increased in a concentration-dependent manner(P<0.05),concentrations of 10 μmol/L,15 μmol/L,and 20 μmol/L of AA were selected for subsequent experiments.Compared with the SEVO group,the levels of TNF-α,IL-6,MDA,ROS,cell apoptosis rate,and expressions of Bax and Caspase-3 proteins in the AA-L,AA-M,and AA-H groups were reduced,the levels of SOD and GSH-Px,red/green JC-1 fluorescence ratio,content of ATP,the expression of Bcl-2 protein,the phosphorylation levels of PI3K and AKT were increased(P<0.05),and were concentration dependent.LY294002 was able to reverse the protective effect of AA on HT-22 cell damage induced by sevoflurane(P<0.05).Conclusion AA protects HT-22 cells from damage induced by sevoflurane by activating the PI3K/AKT signaling pathway,which provides a theoretical reference for the development of novel drugs to reduce sevofluran-induced neurotoxicity.

Objective:To evaluate the efficacy and safety of Xiao′er Huangjin Zhike Granules in the treatment of cough caused by acute bronchitis in children, which is defined in TCM terms as a syndrome of phlegm-heat obstructing the lung.Methods:This was a block-randomized, double-blind, placebo-controlled, multicenter clinical trial.From January 2022 to September 2023, 359 children aged 3 to 7 years old diagnosed as acute bronchitis (lung-obstructing phlegm-heat syndrome) were enrolled from 21 participating hospitals and randomly assigned to the experimental group and placebo group in a 3︰1 ratio, and respectively treated with Xiao′er Huangjin Zhike Granules and its matching placebo.Cough resolution/general resolution rate after 7 days of treatment was used as the primary efficacy outcome for both groups.Results:(1)On the seventh day of treatment, the rate of cough disappearance/basically disappearance in the experimental group and placebo group were 73.95% and 57.61% retrospectively, which had statistically significance ( P=0.001).(2)After 7 days of treatment, the median duration of cough disappearance/basic disappearance were 5 days and 6 days in the two groups , with a statistically significant difference ( P=0.006).The area under the curve of cough symptom severity time was 7.20 ± 3.79 in the experimental group and 8.20±4.42 in the placebo group.The difference between the two groups was statistically significant ( P=0.039).(3) After 7 days of treatment, the difference between TCM syndrome score and baseline was -16.0 (-20.0, -15.0) points in the experimental group and -15.0 (-18.0, -12.0) points in the placebo group, with significant difference between the two groups ( P=0.004).In the experimental group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 49.04%, 28.35%, 16.48% and 6.13% severally; and in the placebo group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 38.04%, 26.09%, 29.35%, and 6.52% separately, which had statistically significant ( P=0.014).(4) There was no significant difference in the incidence of adverse events or adverse reactions during the trial between both groups.Moreover, while adverse reactions in the form of vomiting and diarrhea were occasionally reported, no serious drug-related adverse event or adverse reaction was reported.(5)The tested drug provided good treatment compliance, showing no statistically significant difference from the placebo in terms of compliance rate. Conclusions:Based on the above findings, it can be concluded that Xiao′er Huangjin Zhike Granules provides good safety, efficacy, and treatment compliance in the treatment of cough caused by acute bronchitis, and lung-obstructing phlegm-heat syndrome, in children.

Objective To investigate the effect of erector spinae plane block on ultrasound-based hemodynamic parameters of the arteries of the four limbs and biochemical stress indicators in patients with thoracoscopic lobectomy. Methods A total of 120 patients with thoracoscopic lobectomy were randomly divided into study group and control group, with 60 cases in each group.The study group received erector spinae plane block during surgery, while the control group received conventional anesthesia measures.Pulmonary function indicators[peak expiratory flow rate (PEFR), forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁)], ultrasound-based hemodynamic parameters of the arteries of the four limbs (maximum systolic velocity, minimum diastolic velocity, mean velocity, arterial pulsatility index, and arterial resistance index), stress indicators[cortisol (Cor), norepinephrine (NE), angiotensin Ⅱ(Ang Ⅱ), and adrenocorticotropic hormone (ACTH)], and analgesic effect were compared between the two groups at different time points[before anesthesia induction (T₀), after extubation (T₁), and after drainage tube removal (T₂)]. Results FEV₁, FVC and PEFR in both groups were significantly lower at T₁ and T₂ than at T₀, and FEV₁, FVC and PEFR in the study group were significantly higher than those in the control group at T₁ and T₂(P < 0.05).The maximum systolic velocity and arterial resistance index in both groups were significantly lower at T₁ and T₂ than at T₀, while the minimum diastolic velocity, mean velocity and arterial pulsatility index were significantly higher at T₁ and T₂ than at T₀(P < 0.05).The maximum systolic velocity and arterial resistance index in the study group were significantly higher than those in the control group at T₁ and T₂, but the minimum diastolic velocity, mean velocity and arterial pulsatility index were significantly lower than those in the control group (P < 0.05).Cor, ACTH, Ang Ⅱ and NE in both groups were significantly higher at T₂ than at T₀, and Cor, ACTH, Ang Ⅱ and NE in the study group were significantly lower than those in the control group at T₂(P < 0.05).The Prince-Henry pain score, effective compression times, and actual compression times in the study group were significantly lower than those in the control group (P < 0.05). Conclusion Application of erector spinae plane block in thoracoscopic lobectomy causes smaller fluctuations in hemodynamic parameters of the arteries of four limbs and biochemical stress indicators, with a better anesthetic effect.

Objective To investigate the effects of esketamine on hypoxic-ischemic myocardial injury in neonatal rats based on glycogen synthase kinase-3β/NOD-like receptor thermal protein domain-containing protein 3 (GSK-3β/NLRP3) pathway. Methods Thirty neonatal rats were randomly divided into sham operation group, model group and esketamine group, with 10 rats in each group. The rats in the sham operation group underwent a median incision in the neck to expose the bilateral common carotid arteries; the rats in the model group and the esketamine group underwent ligation of the common carotid arteries combined with a hypoxic environment to establish a model ofischemia and hypoxia; the rats in the esketamine group were given esketamine intervention (50 mg/kg). Left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), serum creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI), lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β levels, myocardial injury, myocardial cell apoptosis and apoptosis protein caspase 1/3/9 levels, neutrophil infiltration in myocardial tissue, and changes in GSK-3β and NLRP3 protein levels in myocardial tissue were detected in each group. Results Compared with the sham operation group, the LVEF and LVFS were significantly decreased and the LVEDD and LVESD were significantly increased in the model group, while the LVEF and LVFS were significantly higher and the LVEDD and LVESD were significantly lower in the esketamine group than in the model group (P < 0.05). The serum levels of CK-MB, cTnI, LDH, TNF-α, IL-6, IL-1β, myocardial injury and apoptosis, caspase 1/3/9 protein levels in myocardial tissue sections, neutrophil counts, and GSK-3β and NLRP3 protein levels were significantly increased in the model group, and these indicators were significantly lower in the esketamine group than in the model group (P < 0.05). Conclusion Esketamine improves hypoxic-ischemic myocardial injury in neonatal rats by inhibiting inflammation, and its mechanism of action is related to the GSK-3β/NLRP3 pathway.

Objective To investigate the effects of perioperative goal-directed fluid therapy (GDFT) on hemodynamics, postoperative recovery, and complications in elderly patientswith gastric cancer radical surgery complicated by hypertension. Methods A total of 88 elderly patients with gastric cancer radical surgery complicated by hypertension were enrolled and randomly divided into treatment group and control group, with 44 patients in each group. The treatment group received GDFT during the perioperative period, while the control group received conventional fluid therapy. The mean arterial pressure, heart rate, and central venous oxygen saturation (ScvO₂) at different time points, as well as postoperative exhaust time, postoperative hospital stay, and postoperative complication rates were compared between the two groups. Results The time effects (F=60.488, 49.789, 39.423), intergroup effects (F=17.317, 12.969, 10.101), and interaction effects (F=26.415, 22.546, 17.294) of mean arterial pressure, heart rate, and ScvO₂ in the two groups showed statistically significant difference(P < 0.05). After surgery, the mean arterial pressure, heart rate, and ScvO₂ in the treatment group were higher than those before anesthesia and the control group (P < 0.05). The postoperative exhaust time and hospital stay in the treatment group were (2.25±0.61) and (10.29±1.96) days, respectively, which were shorter than (2.82±0.71) and (12.36±2.29) days in the control group (P < 0.05). The total incidence of postoperative complications in the treatment group was lower than that in the control group (11.36% versus 29.54%, P < 0.05). Conclusion Applying GDFT during the perioperative period for elderly patients with gastric cancer radical surgery complicated by hypertension can provide a more stable hemodynamic environment, improve tissue perfusion, accelerate postoperative recovery, and reduce postoperative complications.

OBJECTIVES: To investigate the role of mitochondrial autophagy disorder caused by deletion of E3 ubiquitin ligase Parkin in neuroinflammation in a mouse model of MPTP-induced Parkinson's disease (PD). METHODS: Wild-type (WT) male C57BL/6 mice and Parkin^-/- mice were given intraperitoneal injections with MPTP or PBS for 5 consecutive days, and the changes in motor behaviors of the mice were observed using open field test. The effects of Parkin deletion on PD development and neuroinflammation were evaluated using immunofluorescence and Western blotting. The changes of the PINK 1/Parkin signaling pathway in the midbrain substantia nigra of the mice were examined to explore the molecular mechanism of Parkin-mediated regulation of mitochondrial autophagy and its effect on neuroinflammation in PD mice. RESULTS: Compared with their WT counterparts, the Parkin^-/- mice with MPTP injections exhibited significant impairment of motor function with decreased TH⁺ neurons, increased α-synuclein (α-syn) accumulation, and increased numbers of GFAP⁺ and I-ba1⁺ cells in the midbrain substantia nigra. Parkin deletion obviously affected PINK1/Parkin-mediated mitochondrial autophagy to result in significantly increased mtDNA and upregulated expressions of STING and NLRP3 inflammatosomes in the midbrain substantia nigra of MPTP-treated transgenic mice. CONCLUSIONS Parkin deletion causes mitochondrial autophagy disorder to accelerate PD progression and exacerbates neuroinflammation in mice by affecting the PINK1/Parkin signaling pathway, suggesting the important role of Parkin in early pathogenesis of PD.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Mice ; Mice, Inbred C57BL ; Male ; Parkinson Disease/genetics* ; Protein Kinases/genetics* ; Mitochondria/metabolism* ; Disease Models, Animal ; Autophagy ; Signal Transduction ; Neuroinflammatory Diseases/metabolism* ; Mice, Knockout ; alpha-Synuclein/metabolism* ; Substantia Nigra/metabolism* ; Mitophagy ; Disease Progression

Macropinocytosis, an evolutionarily conserved, actin-dependent form of endocytosis, is involved in various physiological processes, including nutrient absorption, antigen presentation, and cell signaling transduction and migration. Oncogene activation and tumor suppressor inactivation induce macropinocytosis in tumors in the digestive system, involved in tumorigenesis and progression, whereas the inhibition of macropinocytosis slows the aggressive phenotype of digestive system tumors and improves the efficacy of anti-tumor drugs. Macropinocytosis can also be used as a delivery route for anti-tumor drugs. Therefore, macropinocytosis has been widely studied to develop new methods for the treatment of digestive system tumors.This paper reviews the role of macropinocytosis in the body, the regulation of macropinocytosis-related signaling pathway, as well as the mechanism of macropinocytosis in colorectal cancer, pancreatic ductal adenocarcinoma, liver cancer and other digestive system tumors, to provide reference for related researches.