OBJECTIVE: To investigate the regulatory effect of electroacupuncture (EA) at "Neiguan" (PC6) on mitochondrial autophagy in rats with myocardial ischemia-reperfusion injury (MIRI) at different phases (ischemia and reperfusion phases), and to explore the bidirectional regulatory effects of EA at "Neiguan" (PC6) and its potential mechanism. METHODS: Forty-five male SD rats were randomly divided into 6 groups according to the random number table method, namely, sham-operation group (n=9), model-A group (n=6), model-B group (n=9), EA-A1 group (n=6), EA-B1 group (n=6), and EA-B2 group (n=9). Except the rats in the sham-operation group, the MIRI model was established in the other groups with the physical ligation and tube pushing method. In the model-A group, the samples were collected directly after ligation, and in the model-B group, the samples were collected after ligation and reperfusion. In the EA-A1 group, EA was delivered while the ligation was performed, and afterwards, the samples were collected. In the EA-B1 group, while the ligation was performed, EA was operated at the same time, and after reperfusion, the samples were collected. In the EA-B2 group, during ligation and the opening of the left anterior descending branch of the coronary artery, EA was delivered, and after reperfusion, the samples were collected. EA was performed at bilateral "Neiguan" (PC6), with a disperse-dense wave, a frequency of 2 Hz/100 Hz, a current of 1 mA, and a duration of 30 min. HE staining was employed to observe the morphology of cardiomyocytes, TUNEL was adopted to detect the apoptosis of cardiomyocytes, transcriptome sequencing was to detect the differentially expressed genes in the left ventricle, JC-1 flow cytometry was to detect the mitochondrial membrane potential (MMP) of cardiomyocytes, Western blot was to detect the protein expression of phosphatase and tensin homolog-induced kinase 1 (Pink1), Parkin and p62 in the left ventricle of rats, and ELISA was to detect the levels of serum creatine kinase isoenzyme (CK-MB) and cardiac troponin I (cTn-I) in the rats. RESULTS: Compared with the sham-operation group, the cardiomyocytes of rats in the model-B group were severely damaged, with disordered arrangement, unclear boundaries, broken muscle fibers, edema and loose distribution; and the cardiomyocytes in the EA-B2 group were slightly damaged, the cell structure was partially unclear, the cells were arranged more regularly, and the intact cardiomyocytes were visible. Compared with the sham-operation group, the apoptosis of cardiomyocytes increased in the model-B group (P<0.001); and when compared with the model-B group, the apoptosis alleviated in the EA-B2 group (P<0.001). The differentially expressed genes among the EA-B2 group, the sham-operation group and the model-B group were closely related to cell autophagy and mitochondrial autophagy. Compared with the sham-operation group, MMP of cardiomyocytes was reduced (P<0.001), the protein expression of Pink1, Parkin, and p62 of the left ventricle and the levels of serum CK-MB and cTn-I were elevated in the model B group (P<0.001). In comparison with model-A group, the MMP of cardiomyocytes and the levels of serum CK-MB and cTn-I were reduced (P<0.001, P<0.05), and the protein expression of Pink1 in the left ventricle rose in the EA-A1 group (P<0.01). Compared with the model-B group, MMP of cardiomyocytes increased (P<0.001), the protein expression of Pink1, Parkin, and p62 of the left ventricle, and the levels of serum CK-MB and cTn-I decreased (P<0.001) in the EA-B1 group and the EA-B2 group. When compared with the EA-A1 group, MMP of cardiomyocytes increased (P<0.001), and the protein expression of Pink1, Parkin, and p62 of the left ventricle, and the levels of serum CK-MB and cTn-I decreased in the EA-B1 group (P<0.01). CONCLUSION EA at "Neiguan" (PC6) can ameliorate MIRI in rats, which may be achieved through the Pink1/Parkin-mediated mitochondrial autophagy pathway. EA can alleviate myocardial injury by enhancing mitochondrial autophagy at the ischemia phase, and it can reduce reperfusion injury by weakening mitochondrial autophagy at the reperfusion phase.
Animals ; Electroacupuncture ; Male ; Myocardial Reperfusion Injury/metabolism* ; Rats, Sprague-Dawley ; Rats ; Acupuncture Points ; Autophagy ; Humans ; Mitochondria/genetics*

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

OBJECTIVES: To investigate the mechanism underlying the therapeutic effect of electroacupuncture (EA) on post-traumatic stress disorder (PTSD) in rats. METHODS: Forty male SD rats were randomized equally into blank control group, PTSD model group, sham-acupuncture group, paroxetine group, and EA group. In the latter 3 groups, the rat models of PTSD, induced by continuous single-prolonged stress and plantar electrical stimulation, were treated with EA at GV20, GV24, BL18 and BL23 acupoints for 15 min (5 times a week for 3 weeks), sham-acupuncture without electrical stimulation, or gavage with paroxetine suspension on the same schedule. Behavioral changes of the rats were evaluated using open field test (OFT) and elevated plus maze (EPM) test. Hippocampal pathologies and neuronal changes were examined with HE and Nissl staining, and mitochondrial ultrastructure was examined using electron microscopy. The mRNA and protein expression levels of Bcl-2, Bax, and caspase-3 were detected by RT-qPCR and immunofluorescence staining. RESULTS: The rat models of PTSD showed significantly reduced total distance traveled in OFT and distance and time spent in the open arms of the EPM, with decreased hippocampal neurons, obvious neuronal and mitochondrial pathologies, decreased hippocampal expression of Bcl-2, and increased Bax and caspase-3 expressions. Treatments with paroxetine and EA both significantly improved behavioral changes of the rat models, increased the number of Nissl-stained neurons, obviously alleviated pathologies in the hippocampal neurons and mitochondrial ultrastructure, increased hippocampal Bcl-2 expression, and lowered caspase-3 expressions. Paroxetine showed significantly better effect than EA for improving performance of the rats in EPM test, whereas sham-acupuncture did not produce any significant improvement. CONCLUSIONS EA alleviates PTSD in rats possibly by upregulating Bcl-2 and downregulating Bax and caspase-3, thereby ameliorating hippocampal mitochondrial damage.
Animals ; Electroacupuncture ; Stress Disorders, Post-Traumatic/metabolism* ; Hippocampus/pathology* ; Rats, Sprague-Dawley ; Male ; Rats ; Mitochondria/pathology* ; Signal Transduction ; bcl-2-Associated X Protein/metabolism* ; Caspase 3/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Disease Models, Animal

Objective Bevacizumab has been clinically used in colorectal cancer,ovarian cancer,cervical cancer,non-small cell lung cancer and other tumor diseases.Common adverse reactions during bevacizumab treatment include albuminuria,thrombosis,bleeding,gastrointestinal perforation and hypertension,among which the incidence of hypertension is as high as 19％-47％.The occurrence of hypertension affects the quality of life of patients,hinds the normal development of tumor treatment,and even induces serious cardiovascular diseases and increases the risk of death,which requires clinical attention.In this paper,the mechanism,influencing factors,prognosis and related treatment of bevacizumab associated hypertension were reviewed,so as to provide reference for clinical rational drug use.

Objective:To investigate the clinical effect of three-dimensional(3D) flap model accurately designed before the operation in repairing irregular wounds of limbs with anterolateral thigh(ALT) perforator flap.Methods:The data of patients with ALT flaps designed with 3D printing technology to repair irregular soft tissue defects of limbs in Suzhou Ruihua Orthopedic Hospital from January to October 2022 were retrospectively analyzed. After the wound was scanned by 3D scanner before surgery, the wound model was printed. The ALT flap was precisely designed and harvested for covering the wound according to the body surface projection of the perforator vessel in the anterolateral femoral region located by color Doppler ultrasound before surgery. The survival of the flap, the healing of the donor and recipient sites and the occurrence of complications were observed and followed up after the operation. The effect of wound repair was evaluated by the comprehensive efficacy evaluation scale of the skin flap. The total score was 100 points, which was divided into excellent (90-100 points), good (75-89 points), fair (60-74 points) and poor (< 60 points).Results:A total of 34 patients were enrolled, including 26 males and 8 females, aged 18-75 years, with an average age of 45.5 years. Injury sites: wrist in 17 cases, foot in 10 cases, ankle in 7 cases. The operation time was 2.0-4.5 h (mean 3.3 h), and all donor sites were sutured directly. Vascular crisis occurred in 2 cases after skin flap transplantation. After surgical exploration, the transplanted skin flap survived, and the other skin flaps survived successfully. All 34 patients were followed up for 6 to 10 months, with an average of 8 months. All the donor sites of the skin flap healed primarily, and the wound healing time of the recipient site was 10-44 days, with an average of 20 days. At the last follow-up, the skin flap was good in color and texture, and the sensation returned to S1 and S2 grades. There were scars left in the donor site, no cicatricial contracture, pain and other discomfort, and no other serious complications. The results of flap evaluation were 80-91 points, with an average of 86 points. Among them, 25 cases were excellent, 6 cases were good, 3 cases were fair, and the excellent and good rate was 91%(31/34).Conclusion:The application of 3D printing technology assisted the design of ALT perforator flap to repair irregular wounds of limbs can significantly reduce the intraoperative design time of the flap, which is in line with the concept of precise design and incision of the flap, and has good clinical effect, and can effectively reduce the trauma and complications of the donor site.

Objective:To investigate the clinical effect of three-dimensional(3D) flap model accurately designed before the operation in repairing irregular wounds of limbs with anterolateral thigh(ALT) perforator flap.Methods:The data of patients with ALT flaps designed with 3D printing technology to repair irregular soft tissue defects of limbs in Suzhou Ruihua Orthopedic Hospital from January to October 2022 were retrospectively analyzed. After the wound was scanned by 3D scanner before surgery, the wound model was printed. The ALT flap was precisely designed and harvested for covering the wound according to the body surface projection of the perforator vessel in the anterolateral femoral region located by color Doppler ultrasound before surgery. The survival of the flap, the healing of the donor and recipient sites and the occurrence of complications were observed and followed up after the operation. The effect of wound repair was evaluated by the comprehensive efficacy evaluation scale of the skin flap. The total score was 100 points, which was divided into excellent (90-100 points), good (75-89 points), fair (60-74 points) and poor (< 60 points).Results:A total of 34 patients were enrolled, including 26 males and 8 females, aged 18-75 years, with an average age of 45.5 years. Injury sites: wrist in 17 cases, foot in 10 cases, ankle in 7 cases. The operation time was 2.0-4.5 h (mean 3.3 h), and all donor sites were sutured directly. Vascular crisis occurred in 2 cases after skin flap transplantation. After surgical exploration, the transplanted skin flap survived, and the other skin flaps survived successfully. All 34 patients were followed up for 6 to 10 months, with an average of 8 months. All the donor sites of the skin flap healed primarily, and the wound healing time of the recipient site was 10-44 days, with an average of 20 days. At the last follow-up, the skin flap was good in color and texture, and the sensation returned to S1 and S2 grades. There were scars left in the donor site, no cicatricial contracture, pain and other discomfort, and no other serious complications. The results of flap evaluation were 80-91 points, with an average of 86 points. Among them, 25 cases were excellent, 6 cases were good, 3 cases were fair, and the excellent and good rate was 91%(31/34).Conclusion:The application of 3D printing technology assisted the design of ALT perforator flap to repair irregular wounds of limbs can significantly reduce the intraoperative design time of the flap, which is in line with the concept of precise design and incision of the flap, and has good clinical effect, and can effectively reduce the trauma and complications of the donor site.

Ketamine,an antagonist of the glutamate N-methyl-D-aspartate(NMDA)receptor,is cur-rently one of the most widely abused psychoactive substances.Prolonged abuse can result in damages to various systems in the body,making it crucial to investigate the regulatory mechanism of ketamine addic-tion and screening related biomarkers.In this study,zebrafish embryos/larvae were initially exposed a-cutely to ketamine.Then,a ketamine addiction model was established in 6-month-old zebrafish through conditioned place preference(CPP)experiments.The zebrafish brain transcriptome was analyzed using RNA-seq,while qPCR and Western blotting were employed to detect the expression of key genes.Results revealed significant reductions in the spontaneous tail coiling,embryo hatching rate,and survival rate of zebrafish embryos in the ketamine-treated group compared to the control group.The distance moved also decreased significantly,from 1904.2 mm in the control group to 319.0 mm in the high dose of ketamine group(300 μmol/L).Conditional positional preference experiments demonstrated that the control ze-brafish did not exhibit significant changes in activity in the CPP tank.In contrast,the ketamine-treated group increased their activity time in the light zone of the tank from 385.2 s before training to 706.4 s af-ter training,representing a 26.8％increase(***P＜0.001).This suggests a preference for ketamine stimulation in zebrafish.KEGG analysis indicated enrichment of differentially expressed genes in the neu-roactive ligand-receptor interaction pathway in the ketamine-treated samples.GSEA analysis further re-veals a significant upregulation of the glutamatergic synapse pathway(NES=1.5).In addition,compared with the control group,the mRNA levels of Grin2b and Gria2 in the ketamine group increased by 4.6 and 1.4 times,respectively,while the protein levels increased by 2.0 and 1.4 times,respectively.These findings suggest that ketamine can induce addiction in zebrafish,potentially through upregulation of the glutamatergic synaptic pathway.

To compare the efficacy, safety and economic cost of endoscopic ultrasound (EUS)-guided puncture sclerotherapy and laparoscopic decapitation decompression for the renal cysts in the upper pole, data of patients with renal cysts in the upper pole who received EUS-guided puncture sclerotherapy (the EUS group, n=9) or laparoscopic decapitation decompression (the laparoscopy group, n=16) in the Second Affiliated Hospital of Soochow University from January 2021 to August 2022 were analyzed retrospectively. The effective rate, operation time, intraoperative blood loss, incidence of complications, hospital stay and treatment cost of the EUS group and the laparoscopy group were compared. Results showed that the effective rate was comparable in the EUS group and laparoscopy group (9/9 VS 14/16, P=0.520). The operation time was shorter (29.8±4.8 min VS 70.1±11.1 min, t=10.207, P<0.001), intraoperative blood loss less (0 mL VS 26.1±5.9 mL, t=13.089, P<0.001), postoperative hospital stay shorter (3.5±0.7 days VS 5.4±2.0 days, t=2.663, P=0.014), and total cost lower (10 547.85±2 388.19 yuan VS 15 316.09±5 352.45 yuan, t=2.517, P=0.019) in the EUS group compared with those in the laparoscopy group. There was no significant difference in the total hospital stay (8.1±2.0 days VS 9.3±3.1 days, t=1.019, P=0.319) or operation cost (3 946.79±490.82 yuan VS 3 860.18±857.42 yuan, t=-0.277, P=0.784) between the EUS group and laparoscopy group. There was 1 case of puncture bleeding, 1 case of hematuria, and 1 case of lumbago in the laparoscopy group, while no complication occurred in the EUS group. In conclusion, it is preliminarily believed that EUS-guided puncture sclerotherapy for renal cysts in the upper pole has similar clinical effects with higher safety, shorter postoperative hospital stay and lower total hospitalization cost compared with those of laparoscopic decapitation decompression, which is worth of clinical promotion.

Objective:To investigate the safety and effectiveness of emergency one-stop hybrid operation in ruptured and hemorrhagic high-grade brain arteriovenous malformations (BAVMs).Methods:Twelve patients with ruptured and hemorrhagic high-grade BAVMs who underwent emergency one-stop hybrid operation were chosen. The clinical data and efficacy of these patients were analyzed retrospectively.Results:All patients completed surgery successfully. Embolization combined with BAVMs resection was performed in 4 patients, BAVMs resection under digital subtraction angiography (DSA) was performed in 4 patients, embolization combined with balloon-assisted BAVMs resection was performed in 1 patient, balloon-assisted BAVMs resection under DSA was performed in 1 patient, embolization combined with BAVMs resection and aneurysm clipping was performed in 1 patient, and BAVMs resection combined with aneurysm clipping under DSA was performed in 1 patient. Intraoperative DSA showed residual vascular malformation in 1 patient and complete resection in other 11 patients. No surgical complications occurred. Two patients presented symptoms of delayed epilepsy after discharge. Six months after operation, 8 patients had good prognosis (Glasgow Outcome Scale [GOS] scores≥4), 4 had poor prognosis (GOS scores of 1-3), and no death occurred. CTA or DSA in all patients 6 months after operation found no residual or recurrent vascular lesions.Conclusion:Emergency one-stop hybrid operation has high complete occlusion rate and low surgical complication incidence in ruptured and hemorrhagic high-grade BAVMs, which is worthy of clinical application.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis