OBJECTIVE: To observe the effects of electroacupuncture (EA) on improving motor function and regulating microglial activation based on Notch receptor 1 (Notch1)/Hes family bHLH transcription factor 1 (Hes1) pathway in mice with Parkinson's disease (PD). METHODS: Thirty-six male C57BL/6 mice were randomly divided into a control group, a model group and an EA group, 12 mice in each group. PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days in the model group and the EA group. From the 1st day of modeling, EA was applied at "Baihui" (GV20) and bilateral "Shenshu" (BL23) in the EA group, with continuous wave, in frequency of 2 Hz and current of 2 mA, 15 min a time, once a day for 14 days continuously. The behavioral performance was evaluated by gait test, pole climbing test and hanging test, the number of positive cells of tyrosine hydroxylase (TH) and the co-expression positive cells of Notch1/ionized calcium binding adaptor molecule 1 (Iba-1) in the substantia nigra of midbrain was assessed by immunofluorescence, the protein expression of TH, α-synuclein (α-syn), Notch1, Hes1, Iba-1, inducible nitric oxide synthase (iNOS), Arginase-1 (ARG1), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10 was detected by Western blot, the mRNA expression of Notch1 and Hes1 was detected by real-time PCR. RESULTS: Compared with the control group, in the model group, the stride frequency was accelerated (P<0.001) and the stride length was shortened (P<0.001) for the four limbs, the pole climbing test time was prolonged (P<0.01) and the grip level was reduced (P<0.01); in the substantia nigra of midbrain, the number of positive cells of TH was decreased (P<0.001), the number of co-expression positive cells of Notch1/Iba-1 was increased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-1βand IL-6 was increased (P<0.01, P<0.05, P<0.001), the protein expression of TH, ARG1 and IL-10 was decreased (P<0.01, P<0.001), the mRNA expression of Notch1 and Hes1 was increased (P<0.01). Compared with the model group, in the EA group, the stride frequency was decelerated (P<0.001) and the stride length was increased (P<0.05, P<0.01, P<0.001) for the four limbs, the pole climbing test time was shortened (P<0.05) and the grip level was increased (P<0.05); in the substantia nigra of midbrain, the number of positive cells of TH was increased (P<0.01), the number of co-expression positive cells of Notch1/Iba-1 was decreased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-6 and IL-1β was decreased (P<0.05, P<0.01), the protein expression of TH, ARG1 and IL-10 was increased (P<0.05, P<0.001, P<0.01), the mRNA expression of Notch1 and Hes1 was decreased (P<0.05). CONCLUSION EA can improve the behavioral performance and protect the dopaminergic neurons in PD mice, its mechanism may relate to the inhibition of Notch1/Hes1-mediated neuroinflammation, thus inhibiting the microglial activation.
Animals ; Electroacupuncture ; Microglia/metabolism* ; Male ; Receptor, Notch1/metabolism* ; Parkinson Disease/physiopathology* ; Transcription Factor HES-1/metabolism* ; Mice ; Mice, Inbred C57BL ; Humans ; Signal Transduction

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*

Objective To explore the mechanism of Yangxue Qingnao Granules(Siwu Decoction modified)in the treatment of hypertension based on network pharmacology and molecular docking.Methods The chemical composition analysis results of Yangxue Qingnao Granules in the early stage of the research group were used as the basis for the screening of active compounds.The oral bioavailability≥30%and drug-likeness≥0.18 were used as the screening conditions,and the blood components were supplemented in combination with the literature.TCMSP,chemical professional database and SWISS database were used to predict the targets of potential active compounds of Yangxue Qingnao Granules.Hypertension-related targets were obtained through GeneCards and DiGSeE databases.The intersection of the targets related to hypertension disease and the targets of the potential active compounds of Yangxue Qingnao Granules(common targets)is the potential target of Yangxue Qingnao Granules for the treatment of hypertension.The potential targets were matched with the potential active compounds of Yangxue Qingnao Granules to obtain the antihypertensive active compounds of Yangxue Qingnao Granules.PPI analysis was performed on the potential targets of serum brain granules in the treatment of hypertension through the STRING database,and the core targets were screened according to the degree value.The David database was used to analyze the GO function and KEGG pathway enrichment of the core targets.The core targets with the top six degrees were selected as the docking target proteins,and molecular docking verification was performed with the antihypertensive active compounds.Results A total of 32 potential active compounds,161 active compound targets and 1 539 hypertension-related targets were obtained.After intersection,88 potential targets(common targets)of Yangxue Qingnao Granules in the treatment of hypertension were obtained,involving 29 antihypertensive active compounds.PPI analysis screened 14 core targets:PPARG,ACHE,IL4,CCL2,JUN,NOS3,APP,IL1B,CAT,PTGS2,CASP3,TP53,TNF,IL6,involving 158 GO entries and 13 signaling pathways.Five key active ingredients,chlorogenic acid,rosmarinic acid,paeoniflorin catechinic acid and aloe emodin,were obtained by molecular docking,which were combined with PTGS2,CASP3,TNF,CAT,TP53 and IL6,respectively.Conclusion Yangxue Qingnao Granules may act on core targets such as PTGS2 and CASP3 through key active components such as chlorogenic acid and rosmarinic acid,regulate key pathways such as TNF signaling pathway,MAPK signaling pathway and Toll-like receptor signaling pathway,and play a role in the treatment of hypertension through anti-inflammatory effects.

Objective:To investigate the application value of laparoscopic natural orifice specimen extraction surgery (NOSES) based on purse-string suture for sigmoid colon and upper rectal cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 14 patients undergoing laparoscopic NOSES based on purse-string suture for sigmoid colon and upper rectal cancer in The First Affiliated Hospital of Sun Yat-sen University from October 2022 to June 2023 were collected. There were 8 males and 6 females, aged (56±10)years. Observation indicators: (1) surgical conditions; (2) postoperative conditions; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD. Count data were described as absolute numbers. Results:(1) Surgical conditions. All patients underwent laparoscopic NOSES based on purse-string suture for sigmoid colon and upper rectal cancer successfully, without conversion to open surgery. The operation time of 14 patients was (162±32)minutes, and the volume of intraoperative blood loss was (22±12)mL. (2) Postoperative conditions. Time to postoperative first out-of-bed activity, time to postoperative first flatus, time to postoperative first drinking, time to postoperative initial liquid food intake, duration of postoperative hospital stay of 14 patients were (1.6±0.7)days, (2.1±0.6)days, (2.4±0.6)days, (3.8±1.0)days, (6.0±0.9)days, respectively. None of patient had perioperative complications such as postoperative anastomotic leakage and bleeding. (3) Follow-up. All 14 patients were followed up for (9.7±1.9)months. There was no postoperative recurrence, metastasis or death in 14 pati-ents.Conclusion:The laparoscopic NOSES based on purse-string suture can be used for sigmoid colon and upper rectal cancer, which is safe and feasible.

Objective To compare therapeutic efficacy of anticoagulation alone and combining with intervention for treating severe cerebral venous thrombosis(CVT).Methods Data of 65 severe CVT patients were retrospectively analyzed.The patients were divided into anticoagulation group(n=32)or combined group(n=33)according to therapeutic methods.The modified Rankin scale(mRS)score at admission and discharge,the prognosis of patients,vascular recanalization rate as well as incidence of complications during follow-up period were compared between groups.Results No significant difference of mRS scores at admission was found between groups(P＞0.05),while mRS scores of combined group were lower than of anticoagulation group at discharge(P＜0.05).The rate of good prognosis at discharge(84.85%vs.59.38%),6 months after discharge(87.88%vs.65.63%)and 12 months after discharge(93.94%vs.75.00%)in combined group were all higher than those in anticoagulation group(all P＜0.05).The vascular recanalization rate in combined group was higher than that in anticoagulant group(100%vs.75.00%,P＜0.05).At the end of follow-up,no significant difference of complication incidence was found between groups(15.15%vs.18.75%,P＞0.05).Conclusion For patients with severe CVT,anticoagulation combined with interventional therapy could significantly alleviate clinical symptoms and improve prognosis compared with anticoagulation alone.

Objective To observe the value of stent implantation for treating idiopathic intracranial hypertension(IIH)complicated with venous sinus stenosis(VSS).Methods Data of 54 patients with IIH complicated with VSS who underwent stent implantation were retrospectively analyzed.The papillary edema grade,lumbar puncture-opening pressure(LP-OP)and trans-stenotic pressure gradient of venous sinus(ΔP)before and after stent implantation were compared,and the symptom improvement and treatment-related complications during the follow-up period were recorded.Results Totally 60 stents were successfully implanted in 54 patients.Before stent implantation,the papillary edema grade was 3(3,3),LP-OP was(391.39±92.62)mmH2O and the ΔP was 18.50(15.00,25.00)mmHg,which decreased to 1(0,1),(208.80±62.31)mmH2O and 1.25(0.88,2.55)mmHg after stent implantation,respectively,all with significant differences(all P＜0.001).Clinical symptoms improved after stent implantation in all 54 patients.At the end of follow-up,disappearance of headache,papillary edema,visual disorder,abducent nerve paralysis and tinnitus were noticed in 30(30/37,81.08%),38(38/45,84.44%),41(41/45,91.11%),8(8/10,80.00%)and 9 cases(9/10,90.00%),respectively.Treatment-related complications occurred in 4 cases(4/54,7.41%),all improved after intervention.Conclusion Stent implantation was effective and safe for treating IIH complicated with VSS.

OBJECTIVE To review the current research progress on pharmacoeconomics evaluation related to spinal muscular atrophy （SMA）， in order to provide valuable insights for clinical treatment， screening and medical insurance payment decision- making. METHODS A computerized search was conducted across multiple databases including PubMed， Web of Science， Embase， Scopus， Cochrane Library， EBSCOhost， CNKI， VIP， CBM and Wanfang database as well as other important health technology assessment （HTA） websites， such as National Institute for Health and Care Research，International Society of Technology Assessment in Health Care， Agency for Healthcare Research and Quality， etc. The pharmacoeconomics evaluation studies related to SMA were collected from the inception to December 31st， 2023. The literature/reports were rigorously screened based on predefined inclusion and exclusion criteria by two researchers， and the essential information from the included literature/ reports was extracted using Excel 2019. The quality of the included literature/reports was evaluated by Consolidated Health Economic Evaluation Reporting Standards 2022. RESULTS Finally， 9 articles and 15 HTA reports were included， with overall good quality of literature， but poor quality of HTA reports. There were a total of 24 studies on the pharmacoeconomics evaluation of SMA， including treatment options such as nusinersen sodium， sovaprevir， risperidone， and best supportive therapy.The review results showed that nusinersen sodium was not cost-effective in the treatment of SMA； there was no consensus on the economic viability of treatment options such as risperidone and sovaprevir； newborn/prenatal screening combined withmedication therapy was cost-effective. CONCLUSIONS newborn/prenatal screening combined with SMA medication therapy demonstrates economic advantages. It is suggested to further investigate the cost-effectiveness of new SMA drugs and SMA screening in China， taking localization parameters and medical insurance prices into account， and gradually incorporate SMA screening into the scope of neonatal genetic disease detection， in order to alleviate the financial burden of patients’ families and healthcare systems.

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

Objective:To investigate the clinical efficacy of oblique intervertebral fusion in the treatment of failed internal fixation of thoracolumbar fractures.Methods:A retrospective study was conducted to analyze the clinical data of 14 patients who had undergone revision surgery for failed internal fixation of thoracolumbar fracture at Department of Orthopedics, The First Hospital Affiliated to Zhengzhou University from January 2014 to December 2021. There were 6 men and 8 women with a mean age of 47.5 (42.0, 54.3) years. Fracture segments: T 12 in 2 cases, L 1 in 3 cases, L 2 in 4 cases, L 3 in 3 cases, and L 4 in 2 cases; AO classification: type A in 1 case, type B in 7 cases, and type C in 6 cases. Their prior surgical method was posterior internal fixation with pedicle screws. The revision surgery consisted of subtotal vertebral resection through the oblique lateral approach, bone column reconstruction and lateral screw-rod internal fixation for intervertebral fusion after posterior internal fixation reset. The operation time, intraoperative bleeding, postoperative hospital stay, and incidence of complications were recorded. Compared were visual analogue scale (VAS) and Oswestry disability index (ODI) scores for low back pain at preoperation, 3 days and 3 months postoperation, and the last follow-up, fusion at the last follow-up, and Frankel grading for neurological function at preoperation and postoperation. Results:All the 14 patients underwent surgery successfully and were followed up for 23 (18, 24) months. The operation time was (175.1±28.2) min, the intraoperative bleeding (300.4±122.6) mL, and the postoperative hospital stay 6 (6, 7) d. One case developed postoperative transient hip flexion weakness but was discharged after restoration of normal muscle strength by conservative treatment. Both VAS and ODI scores for low back pain at all postoperative time points were significantly improved compared with the preoperative values ( P<0.05), with a significant trend of 3 days postoperation >3 months postoperation > the last follow-up ( P<0.05). In the 12 patients with preoperative neurological damage, the Frankel grading rose by at least 1 level postoperatively ( Z=-3.110, P=0.002). The last follow-up revealed no loosening or fracture of the internal fixation. Complete bony fusion was visible in all CT sagittal reconstructions. Conclusion:For patients with thoracolumbar fracture undergoing failed internal fixation, oblique intervertebral fusion is an alternative minimally invasive surgical treatment due to its satisfactory overall outcomes.

Humans ; Female ; Deep Learning ; Ovarian Neoplasms/genetics* ; Carcinoma, Ovarian Epithelial/genetics* ; Neural Networks, Computer ; RNA