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Objective:To research the efficacy and safety of robotic thyroidectomy and bilateral modified radical neck dissection through bilateral axillo-breast approach (BABA) .Methods:We retrospectively analyzed the clinical data of 37 patients with thyroid cancer who received bilateral modified radical neck dissection through the BABA at the Department of Thyroid and Breast Surgery of the 960th Hospital of the People’s Liberation Army from Jan. 2014 to Jan. 2023. There were 24 females and 13 males, and the average age of the patients was (33,22±10.53) years old. The tumor diameter, number of lymph node dissection and metastasis in the central and lateral regions, average operation time, average hospital stay, complications, and aesthetic score were recorded. SPSS 25.0 software was used for statistical analysis, and the measurement data was calculated using mean ± standard deviation ( ± s), and the counting data was expressed in percentages and numbers. Results:A total of 37 thyroid cancer patients underwent robotic bilateral regional lymph node dissection. The 37 patients received total thyroidectomy, bilateral central compartment and cervical lateral regional lymph node dissection. All the pathological types were papillary carcinoma, with a maximal tumor diameter of (1.47±0.85) cm. The average number of central lymph nodes dissected was 19.46±8.84, and there were (10.24±5.95) metastases; The average number of lymph nodes removed from the bilateral cervical region was 38.92±14.21, and there were (7.92±5.84) metastases. The average operation time was (288.05±77.09) min, the average length of stay in the hospital was (10.76±3.92) days, and the average length of stay in the hospital following surgery was (8.03±2.08) days. These patients had no permanent hypoparathyroidism, permanent recurrent laryngeal nerve palsy, infection, accessory nerve injury and phrenic nerve injury after operation. Transient hypoparathyroidism occurred in 15 patients, transient recurrent laryngeal nerve palsy occurred in 1 patient, and chyle leak occurred in 2 patients. One month after surgery, the aesthetic score was 9.51±0.69.Two patients were found lymph node metastases during the (27.81±15.10) months of follow-up, and received robotic cervical lymph node dissection with BABA.Conclusion:For carefully chosen thyroid cancer patients with bilateral lateral cervical region lymph node metastases, robotic bilateral cervical lymph node regional dissection via BABA is safe and feasible, and good cosmetic results can be obtained.
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ObjectiveTo investigate the effects of Linggui Zhugantang on mitochondrial fission and fusion and silencing information regulator 3（Sirt3）/adenosine monophosphate dependent protein kinase （AMPK） signaling pathway in chronic heart failure （CHF） rats after myocardial infarction （MI）. MethodSD rats randomly divide into sham operation group （normal saline ，thread only without ligature）， model group （normal saline， ligation of the left anterior descending coronary artery proximal to the heart）， Linggui Zhugantang group （4.8 g·kg-1） and Captopril group （0.002 57 g·kg-1）， with 10 rats in each group. Administere drug continuously for 28 days. Echocardiography detected cardiac function parameters. Hematoxylin eosin （HE） staining observed the pathological changes of the heart. Immunofluorescence detected the levels of reactive oxygen species （ROS）. JC-1 detect mitochondrial membrane potential. Colorimetry measure adenosine triphosphate （ATP）， superoxide dismutase （SOD）， malondialdehyde （MDA）， mitochondrial respiratory chain complex activity （Ⅰ-Ⅳ）. TdT-mediated dUTP nick end labeling （TUNEL） staining detected the apoptosis rate of myocardial tissue. Western blot detected protein expression levels of Sirt3， phosphorylated AMPK （p-AMPK）， phosphorylated dynamic-related protein 1（p-Drp1）， mitochondrial fission protein 1（Fis1）， mitochondrial fission factor （MFF）， optic atrophy protein 1（OPA1）. ResultCompared to the sham group， the left ventricular end diastolic diameter （LVIDd） and left ventricular end systolic diameter （LVIDs） were significantly increased in model group （P<0.01）， while the left ventricular short axis shortening rate （LVFS） and left ventricular ejection fraction （LVEF） were significantly decreased （P<0.01）. There were inflammatory cell infiltration and obvious pathological injury in myocardial tissue. ROS， MDA levels and myocardial cell apoptosis rate were significantly increased （P<0.01）， SOD level， ATP content， and membrane potential were significantly decreased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） was significantly decreased （P<0.01）. Levels of p-Drp1， Fis1， MFF proteins were significantly up-regulated （P<0.01）， while Sirt3， p-AMPK， OPA1 proteins level were significantly down-regulated （P<0.01）. Compared with model group， LVIDd and LVIDs were significantly decreased （P<0.01）， LVEF and LVFS were significantly increased （P<0.01）. Inflammatory cell infiltration and pathological damage of myocardial tissue were significantly relieved. ROS， MDA levels and myocardial cell apoptosis rate were significantly decreased in Linggui Zhugantang group and Captopril group （P<0.01）， SOD level， ATP content， and membrane potential significantly increased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） increased significantly （P<0.01），and p-Drp1， Fis1， MFF protein levels were significantly down-regulated （P<0.01）， Sirt3， p-AMPK， OPA1 protein were significantly up-regulated （P<0.01）. ConclusionLinggui Zhugantang can alleviate oxidative stress and apoptosis damage of myocardial cells， maintain mitochondrial function stability， and its effect may be related to mitochondrial mitosis fusion and Sirt3/AMPK signaling pathway.
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OBJECTIVE To investigate the effects and mechanism of polysaccharides from Hedyotis diffusa （HDP） on isoniazid （INH）-induced liver injury. METHODS Healthy transgenic zebrafish with liver-specific fluorescence were divided into normal group， model group （4 mmol/L INH）， HDP low-concentration group （4 mmol/L INH+50 mg/mL HDP） and HDP high- concentration group （4 mmol/L INH+100 mg/mL HDP）. After grouping treating， the liver fluorescence area， fluorescence intensity and pathological changes of liver tissue were observed. Human liver L02 cells were divided into normal group， model group （4 mmol/L INH）， HDP low-concentration group （4 mmol/L INH+2 mg/mL HDP）， and HDP high-concentration group （4 mmol/L INH + 4 mg/mL HDP）. After grouping treating， the cell viability was detected， and the levels of alanine transaminase （ALT）， aspartate transaminase （AST）， and the content of glutathione （GSH） as well as the expression levels of silent information regulator 1 （Sirt1）， nuclear factor-erythroid 2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1） and quinone oxidoreductase 1 （NQO1） proteins were detected. RESULTS Compared with the model group， the HDP low- and high-concentration groups showed varying degrees of increase in the fluorescence area and fluorescence intensity （except for HDP low-concentration group） of zebrafish liver （P＜0.05 or P＜0.01）， and the characteristics of liver injury and necrosis had been improved to varying degrees. Compared with model group， the survival rate of L02 cells， the content of GSH （except for HDP low-concentration group）， the protein expression levels of Sirt1 （except for HDP low-concentration group）， Nrf2， NQO1， HO-1 （except for HDP low-concentration group） were significantly increased in HDP low- and high-concentration groups （P＜0.05 or P＜0.01）， and the levels of ALT and AST （except for HDP low-concentration group） were significantly decreased （P＜0.05）； the number of survival cells significantly increased， while the number of damaged or dead cells significantly decreased. CONCLUSIONS HDP has a potential protective effect against INH-induced liver injury， the mechanism of which may be associated with activating Sirt1/Nrf2 signaling pathway， improving mitochondrial function and enhancing antioxidant capacity.
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18F-FDG PET/CT is one of the most advanced diagnostic methods for lymphoma, which plays an important role in the diagnosis, efficacy evaluation, prognosis prediction and clinical decision-making of lymphoma. Radiomics, which uses complex bioinformatics methods to extract quantitative information from medical images to characterize tumor heterogeneity, has blossomed over the past decade. Radiomics has been applied to 18F-FDG PET/CT to quantify the heterogeneity within tumors, which has great potential and value in the study of lymphoma. This article reviews the research progress and application of 18F-FDG PET/CT radiomics in lymphoma.
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Objective:To compare the clinical efficacy and safety of hemoperfusion (HP) and gammaglobulin on the treatment of Henoch-Sch?nlein purpura (HSP) with gastrointestinal bleeding in children.Methods:Case-control study.A total of 39 HSP children combined with gastrointestinal bleeding diagnosed in the Department of Pediatric Nephrology, Rheumatology and Immunology, Shengjing Hospital of China Medical University from January 2015 to December 2019 were retrospectively recruited.They were divided into the HP group and the gammaglobulin group according to the therapeutic strategy.Clinical data were collected, and a 6-month follow-up survey was conducted for monitoring the relapse of gastrointestinal bleeding and the occurrence of kidney injury.The differences between groups were compared by Fisher′s exact test, two independent samples t-test, Mann-Whitney U-test, Kruskal-Wallis H-test, and One-Way ANOVA. Results:(1) There were 20 cases in the HP group and 19 cases were included in the gammaglobulin group.The gammaglobulin group was younger than the HP treatment group.(2) In addition to gastrointestinal bleeding, children in both groups had other clinical symptoms, such as abdominal pain, angioneurotic edema, and hematuria.(3)Comparison of laboratory indexes: Inflammatory indexes: white blood cell count (WBC), C-creative protein (CRP) and coagulation function indexes: fibrin degradation products (FDP), D-dimer (DD) were significantly elevated before treatment in the 2 groups, and there was no difference between the 2 groups ( P>0.05); WBC, CRP and FDP, DD declined in the 2 groups after treatment compared with the former, and there was no difference between the 2 groups ( P>0.05); (4) Comparison of clinical manifestations: when HP was applied with gammaglobulin in the treatment window within 3 d, the difference in the time of abdominal pain relief in the HP group was shorter than that of the gammaglobulin group [1.00(1.00, 1.00) d vs.2.00(1.75, 6.50) d, P=0.011]; comparing the time of gastrointestinal bleeding stopping when HP was applied with gammaglobulin comparison, the difference in gastrointestinal bleeding cessation time was not statistically significant ( P>0.05); (5) Comparison of hospitalization time: within 3 d application of HP compared with other window period hospitalization time were significantly reduced [(16.89±4.99) d than (19.20±2.39) d than (34.83±8.40) d, both P<0.05]; (6) Comparison of hospitalization costs: within 3 d application of HP compared with other window period hospitalization costs were significantly reduced [25 554.03 (22 168.61, 28 527.30) yuan than 33 619.48 (32 661.18, 36 971.47) yuan than 51 290.34 (34 163.04, 64 772.66) yuan, both P<0.05]; There were no statistically significant difference in the hospitalization time and hospitalization cost between and within the gammaglobulin group (all P>0.05); (7) Comparison of hormone dosages: the difference in the results of the initial dose of hormone use, pre-treatment dose of gammaglobulin/HP, and post-treatment dose of gammaglobulin/HP between the two groups of children was not statistically significant(all P>0.05). Safety profile was comparable between groups.The difference in hormone dosage before and after treatment within the gammaglobulin and HP treatment group was statistically different ( P<0.001). Conclusions:For children with severe HSP accompanied by gastrointestinal bleeding, early treatment with blood purification can rapidly relieve clinical symptoms and reduce the number of hospital days and hospitalization costs.For cases where blood purification is not available or suitable, gammaglobulin treatment is another option.
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BACKGROUND:The low catalytic activity and lack of targeting of commonly used metal ions have severely limited the clinical application of chemodynamic therapy in tumor treatment.On the other hand,although the composite nanoplatforms are endowed with tumor-targeting functions by surface functionalization,the lack of tumor microenvironment acidity also severely weakens the efficacy of chemodynamic therapy. OBJECTIVE:To prepare novel composite nanoplatforms and assess their feasibility to enhance the effects of chemodynamic therapy at the cellular level. METHODS:SLC-0111-loaded zeolite imidazole framework-8 doped with divalent iron ions(Fe2+)and divalent cobalt ions(Co2+)(Fe-Co/ZIF-8@SLC-0111)was synthesized by ion-exchange reaction and self-assembly,and loaded with hyaluronic acid(HA)by electrostatic adsorption,followed by obtaining the target nanoparticles Fe-Co/ZIF-8@SLC-0111-HA(abbreviated as FC-S).Meanwhile,nanoparticles Fe-Co/ZIF-8-HA(abbreviated as FC)without SLC-0111 were synthesized by the same method.The nanocomposite platform was tested for particle size,zeta potential,surface morphology,in vitro reactive oxygen species generation,and ability to consume glutathione.Human osteosarcoma cell MG-63 and mouse fibroblast cell L929 were used as experimental subjects.The cytotoxicity of FC-S was detected by CCK-8 assay.Human osteosarcoma cell MG-63 was used as the experimental object to detect the cell internalization of FC-S.In addition to H2O2,the effects of FC-S and FC on intracellular pH,carbonic anhydrase 9 protein expression,cell viability and apoptosis,intracellular reactive oxygen species and glutathione content,and mitochondrial membrane potential were investigated. RESULTS AND CONCLUSION:(1)The FC-S composite nanoplatform was successfully prepared with a well-defined rhombic dodecahedral structure,uniform size and good dispersion.Its particle size was about 323 nm;zeta potential was about-11.1 mV,and the nanoplatform had a certain reactive oxygen species generation capacity in vitro.(2)FC-S nanoplatforms accumulated intracellularly in a time-dependent manner and could successfully escape from lysosomes.When the mass concentration of FC-S was≤20 μg/mL,there was no obvious cytotoxicity to MG-63 cells and L929 cells,and 20 μg/mL FC-S was selected to act on MG-63 cells in subsequent experiments.(3)Compared with FC group,the protein expression of carbonic anhydrase 9 in MG-63 cells in FC-S group was decreased(P<0.01);the intracellular acidic environment was enhanced;the content of reactive oxygen species was increased(P<0.001);the mitochondrial damage was aggravated;the number of dead cells was increased,and the apoptosis rate was increased(P<0.001).(4)The results indicate that FC-S,as a novel composite nanoplatform,can effectively improve the weakly acidic microenvironment in tumor cells and enhance the level of intracellular reactive oxygen species production,thus enhancing the efficacy of chemodynamic therapy.
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Gastric cancer poses a serious threat to the health of people.Despite the continuous breakthroughs in the development of new drugs such as chemotherapy,targeted therapy and immunotherapy in recent years,radical surgery remains the cornerstone in the treatment of gastric cancer.With the establishment of standard gastric cancer surgery,the advancement of minimally invasive surgical techniques represented by laparoscopy,the determination of perioperative comprehensive treatment of advanced gastric cancer and the formation and initial practice of precise surgical concepts for gastric cancer,the progress of surgical treatment for gastric cancer is advancing by leaps and bounds.The concepts of individualized and optimal treatment are gradually taking root.Safety,effectiveness,precision and minimally invasive approaches have always been the inherent laws of discipline development firmly grasped by gastric cancer surgeons.In order to facilitate better growth for young doctors,the author summarized the latest developments in the diagnosis and treatment of gastric cancer and looked ahead to future trend.
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@#Objective To compare and analyze the efficacy and safety of 5-needle injection and standard 20-needle injection in the treatment of overactive bladder with botulinum toxin type A.Methods A retrospective analysis was performed on 48 patients with overactive bladder who received intravesical injection of botulinum toxin type A in the Department of Urology,Hangzhou Third People's Hospital from January 2015 to December 2022,and they were divided into two groups according to the number of injections,with 24 patients in each group.The observation group received 5-needle injection,and the control group received standard 20-needle injection.Average daily frequency of urination,international consultation on incontinence questionnaire-overactive bladder,international consultation on incontinence questionnaire-overactive bladder(ICIQ-OAB)score,overactive bladder(OAB-Q)score,visual analogue scale(VAS),patient generated index(PGI-I)score,complication rate and willingness to repeat injection were recorded before and after treatment in two groups,respectively.Results There were no significant differences in age,gender,course of disease,average daily frequency of urination before treatment and baseline data of each score between the two groups,which were comparable.All patients completed treatment,and compared with before treatment,the mean daily frequency of urination,ICIQ-OAB and OAB-Q were improved after treatment(P<0.05),there was no significant difference between the two groups(P>0.05).There were no significant differences in scores and incidence of complications between the two groups after treatment(P>0.05).However,patients in the observation group were more willing to receive another injection(P<0.05).Conclusion The efficacy and safety of 5-needle vesical injection of botulinum toxin type A in the treatment of overactive bladder is similar to that of standard 20-needle injection,which is more easily accepted by patients,and is a safe and effective alternative to standard technique.
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Background The serious air pollution of highway toll booths poses a high occupational exposure risk to toll collectors. It is urgent to develop purification methods suitable for airborne particles and microbial pathogens in highway toll booths. Objective To verify the purification effect of low temperature plasma air purifiers on airborne particles and microbes in highway toll booths. Methods Based on controlled-intervention design, we selected three toll booths in an expressway toll station as on-site experimental locations for 6 d (no-intervention period: the low-temperature plasma purifier was turned off in the first three days; intervention period: the purifier was turned on from 9:00 to 17:00 in the following three days). The indoor and outdoor PM2.5 and PM10 concentrations were continuously monitored during the study. At 9:00, 12:00, and 17:00 of every day during the experiment, indoor and outdoor air samples were collected to analyze the concentration of airborne culturable colonies with a plankton sampler. Airborne particle samples were collected in the outermost exit continuously from 9:00 to 17:00 every day during the experiment using a medium flow particulate sampler, and the species and relative abundance of fungi and bacteria contained in the samples were analyzed by gene sequencing. Independent-sample t test was used to compare the concentration of indoor PM2.5, PM10, and culturable colonies between the intervention period and the non-intervention period. α diversity analysis, β diversity analysis, and t test were used to compare the diversity and relative abundance of specific species of bacteria and fungi, as well as typical pathogenic bacteria and fungi in the samples between the non-intervention period and the intervention period to reflect the purification effect of low temperature plasma air purifier on airborne PM2.5, PM10, and microorganisms. Results During the intervention period, the mean indoor concentrations of PM2.5, PM10, and culturable colonies were lower than those of the no-intervention period (P<0.01 or P<0.001). The ratios of indoor to outdoor concentration (I/O) of PM2.5 and PM10 during the intervention period were significantly lower than those of the no-intervention period (P<0.001), except the I/O of culturable colonies. Compared with the average concentration at 9:00, the average cleaning rates at 12:00 and 17:00 for PM2.5 were 49.0% and 46.1%, for PM10 were 49.7% and 45.4%, for airborne culturable colonies were 50.8% and 49.9%, respectively. The β diversity analysis showed that there were significant differences in composition at the level of species of bacteria, and at the levels of genus and species of fungi between the intervention and the no-intervention periods. The relative abundances of 10 species of bacteria such as Lactobacillus and 7 species of fungi such as Torula in the intervention period were significantly lower than those in the non-intervention period, but the relative abundances of fungi such as unclassified_f_cladosporiaceae, trichomerium, and cercospora were higher (P<0.05). For typical pathogenic bacteria, the relative abundances of Lactobacillus and Clostridium_sensu_stricto_1 during the intervention period were 73.5% and 86.9% lower than those in the no-intervention period, and the relative abundance of Talaromyces was 53.5% lower (P<0.05). Conclusion Low temperature plasma air purifier has a good purification effect on indoor PM2.5, PM10, and culturable colonies in highway toll booths, and likely a limited effect on some fungi.
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Objective:To explore the safety and feasibility of bilateral axillo-breast approach （BABA） robot in the operation of thyroid cancer in obese women. Methods:The clinical data of 81 obese female patients who underwent da Vinci robotic thyroid cancer surgery（robotic group） at the Department of Thyroid and Breast Surgery, PLA 960 Hospital from May 2018 to December 2021 were retrospectively analyzed and compared with the clinical data of 106 obese female thyroid cancer patients who underwent open surgery（open group） during the same period. The age, body mass index（BMI）, mean time of surgery, mean postoperative drainage, tumor diameter, postoperative tumor stage, number of lymph node dissection in the central and lateral cervical regions, number of positive lymph nodes in the central and lateral cervical regions, postoperative cosmetic outcome satisfaction score, mean postoperative hospital stay and postoperative complications of all patients were counted. The results were analyzed using SPSS 26.0 statistical software, and the count data were compared using the χ² test, and the measurement data were compared using the t test. Results:All patients completed the operation successfully, and there was no conversion in the robot group, postoperative pathological results were all composed of papillary thyroid carcinoma. The operation time in the robot group was（144.62±36.38） min, which was longer than that in the open group（117.06±18.72） min（P<0.05）. The average age of the robot group was（40.25±9.27） years, which was lower than that of the open group（49.59±8.70） years（P<0.05）. The satisfactory score of cosmetic effect in the robot group（9.44±0.65） was higher than that in the open group（5.23±1.07）（P<0.05）. There was no significant difference in tumor diameter, BMI, average postoperative drainage, temporary hypoparathyroidism and recurrent laryngeal nerve injury, number of central and lateral cervical lymph node dissection, number of positive lymph nodes in the central and lateral cervical regions, and average postoperative hospital stay between the two groups. There was no permanent hypoparathyroidism and recurrent laryngeal nerve injury in both groups. Conclusion:The application of BABA pathway robot in thyroid cancer surgery in obese women is safe and feasible, and the cosmetic effect is better after operation.
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Humans , Female , Adult , Middle Aged , Robotics/methods , Retrospective Studies , Recurrent Laryngeal Nerve Injuries , Thyroidectomy/methods , Carcinoma, Papillary/surgery , Thyroid Neoplasms/pathology , Neck Dissection , Treatment OutcomeABSTRACT
Objective:To observe the application of near-infrared autofluorescence imaging (NIRAF) technology combined with carbon nanoparticle (CNP) negative imaging in identification of parathyroid gland (PG) during thyroid carcinoma surgery.Methods:80 patients with thyroid cancer who underwent total thyroidectomy + central lymph node dissection performed by the same experienced physician team at the 960th Hospital of the PLA from Jan. to Mar. 2022 were prospectively included. Before operation, they were divided into two groups using random number table method before surgery: control group (40 cases) using CNP negative imaging, and experimental group (40 cases) using CNP negative imaging combined with NIRAF technique for intraoperative identification of PG. The gold standard for the identification of parathyroid glands was to compare the amount of intraoperative discovery retention misresection and transplantation of PG and the number of postoperative parathyroid hormone (PTH) and the number of complications in the two groups by immune colloidal gold technique. SPSS 25.0 software was used for statistical analysis.Results:All patients in the two groups were successfully operated and followed up. 137 149 PG were found and confirmed in the control group and the observation group, 108 132 PG were retained in situ and 29 17 PG were transplanted, the differences were statistically significant (all P <0.05) ; The number of A1 PG was 103 and 109, respectively. Among them, 84 102 were retained in situ and 19 7 were transplanted, the difference was statistically significant ( P <0.05) . There was no significant difference in the amount of A2 type PG and B type PG between the two groups ( P >0.05) . No A3 type PG was found in the two groups, and a total of 3 A3 types of PG were confirmed in postoperative pathological reports. There were no significant differences in misresection in the control group and the observation group, 5 and 2 PG were mistakenly cut, respectively (all P >0.05) . The PTH 1 day after surgery was 17.7 (5.6,30.4) pg/mL in the control group and 21.7 (12.8,38.3) pg/mL in the observation group, the difference was statistically significant ( P<0.05) . There were no significant differences in the levels of serum calcium and serum phosphorus 1 day after operation and PTH 1 month after surgery between the two groups (all P > 0.05) . Conclusion:Compared with CNP alone, combined with NIRAF technique can quickly and effectively identify PG, and PG can be better protected in situ and postoperative hypoparathyroidism can be reduced.
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Aim To investigate whether Linggui Zhugan Decoction ( LGZGD) can inhibit ventricular remodeling and prevent heart failure in rats after myocardial infarction by regulating Nrf2/BNIP3 pathway. Methods The model of heart failure after myocardial infarction was established by left coronary artery ligation in rats. Two weeks after modeling, all rats were randomly divided into model group, LGZGD group, and captopril group. Meanwhile sham operation group was set up. The rats were given continuous intragastric administration with drug or distilled water for 28 days, once a day. The behavioral signs of rats in each group were observed. The cardiac function of rats in each group was examined by echocardiography. Serum BNP and NT-ProBNP content were detected by enzyme -linked immunoassay; The changes of myocardial his-topathological and collagen fibers in rats were detected using sirius staining. The contents of oxidative stress index including ROS, SOD in myocardial tissue of rats in each group were observed by DCFH-DA fluorescent probe and Enzyme-linked immunoassay. The ultra-structure of mitochondria was observed by transmission electron microscopy. Expressions of apoptotic proteins ( mitochondrial CytC, cytoplasmic CytC) were detected by Western blot. Expression of proteins related to the Nrf2/BNIP3 pathway were examined by immunofluorescence and Western blot. Results LGZGD could significantly improve the cardiac function of rats, reduce the contents of BNP and NT-ProBNP, inhibit the excessive deposition of collagen in myocardial interstiti-um, reduce ROS, increase the content of SOD, improve mitochondrial structure damage, up-regulate the expression of Nrf2 and nuclear translocation, and reduce the expression of BNIP3. Conclusions LGZGD can inhibit the ventricular remodeling and prevent the occurrence of heart failure after myocardial infarction. Its pharmacological effects are mainly related to regulating the Nrf2/BNIP3 pathway, activating Nrf2, promoting its nuclear transfer, and further down-regulating BNIP3, protecting mitochondrial function, and reducing cardiomyocyte apoptosis.
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Aim To investigate the effect of YTHDF2 on the proliferation and migration of activated hepatic stellate cells(HSCs). Methods 5 jjLg • L
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[Abstract] Objective To study whether the regulation of mammalian target of rapamycin complex 2(mTORC2) / Akt signaling pathway has a protective effect on SH-SY5Y cell line damaged by 6-hydroxydopamine (6-OHDA), and to clarify its molecular mechanism. Methods SH-SY5Y cells treated with retinoic acid (RA) were given 6-OHDA, mTORC2 signaling pathway inhibitor PP242 and agonist A-443654 respectively. The changes of cell number in each group were investigated by immunofluorescent staining; The total protein was extracted and the expression level and interaction of key proteins in mTORC2 signaling pathway were determined by Western blotting and co-immunoprecipitation (CoIP); The apoptosis rate of cells in each group was detected by flow cytometry. At the same time, the co-culture Parkinson’ s disease (PD) model was made using SH-SY5Y cell line and Bv-2 cell line; MTT colorimetric method was used to detect the cell viability of each group; ELISA was used to detect the content of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in cell culture supernatant. Results The number of tyrosine hydroxylase(TH) / proliferating cell nuclear antigen (PCNA) / hochest-, TH / 5-bronmo-2’ -deoxyuridine(BrdU) -labeled positive cells in 6-OHDA-lesioned PD cell model group was significantly lower than that in the normal group; The apoptosis rate was higher; The expression of Rictor, p-Akt and regulated in DNA damage and development 1(REDD1) was increased; There was an interaction between Rictor and p-Akt or REDD1; The cell viability was significantly reduced in the co-culture model; the content of TNF-α and IL-β increased in the cell culture supernatant. With further up-regulation of the abovementioned protein expressions, the cell survival, apoptosis and pro-inflammatory cytokine levels in A-443654 group were significantly ameliorated, while PP242 group showed the opposite changes. Conclusion A-443654 activates mTORC2 signaling pathway by p-Akt, which increases the expression of Rictor and REDD1 protein. These changes contribute to the amelioration in cell survival rate, apoptosis rate, and the proliferation and differentiation and decreasion of apoptosis rate of SH-SY5Y cells. These result improved 6-OHDA-induced cell damage and inhibited the release of pro-inflammatory cytokines.
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Objective To explore the effect of activation of mammalian target of rapmycin complex 2(mTORC2)/Akt signaling pathway on dopaminergic neurons and behavior in 6-hydroxydopamine (6-OHDA) model mice and its possible mechanism. Methods Selecting 36 mice which The Nestin-CreERTM and ROSA26-LacZ reporter genes were detected at the same time in 3-month-old male C57BL/6J mice weighing 20-25 g divideng them into 4 gruops, NS+ corn oil group, 6-OHDA+corn oil group, 6-OHDA+PP242 group and 6-OHDA+A-443654 group, and 6-OHDA was injected into the right striatum of the brain to replicate the Parkinson’s disease (PD) model of mice, and then daily intraperitoneal injection of mTORC2/Akt signaling pathway agonist A-443654 or inhibitor PP242. Serum interleukin-1β (IL-1β) and tumor necrosis factor-α(TNF-α)levels were measured by enzyme-linked immunosorbent assay. Immunohistochemistry and immunofluorescence staining were performed to investigate the change of microglia, dopaminergic neurons as well as neural progenitor cells (NPCs). Western blotting was used to detect the expression of related protein of mTORC2/Akt signaling pathway including rictor, p-Akt and regulated in development and DNA dgmage responses 1(REDD1) and the interaction between them were verified by immunoprecipitation. Finally, the behavioral performance of each group of mice was observed. Results With the activation of microglia and the increase of inflammatory factors in PD model mice, the number of dopaminergic neurons in the substantia nigra(SN) decreased significantly, and the motor function of the mice was impaired, but the number of NPCs increased significantly compared with the control mice, mTORC2/Akt signaling pathway related protein expression was also significantly up-regulated. A-443654 treatment further up-regulated the expression of these proteins, meanwhile the indicators mentioned above were ameliorated. However, the inhibitor PP242 treatment group showed completely opposite result with the agonist group. Conclusion A-443654 can promote the proliferation of NPCs and the number of new-born dopaminergic neurons by up-regulating related proteins of mTORC2/Akt signaling pathway, and reducing the activation of microglia and the level of inflammation factors, which ultimately lead to the amelioration of SN-striatal dopaminergic neurons and behavioral performance in PD model mice.
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Objective To investigate the repairing effect of ursolic acid extracted from Hippophae rhamnoi-des L.on sciatic nerve injury in rats.Methods After preparing a sciatic nerve damage model,thirty 2-month old Wistar rats were randomly divided into ursolic acid and control groups,with 15 rats in each group.Ursolic acid group was given Ursolic acid 150 mg/(kg·d)by gavage,while the control group was given the same dose of normal saline for 6 weeks.After 6 weeks,H&E staining was used to observe the pathological changes of rat sciatic nerves,and SFI and MNCV were calculated;The expression of NGF in sciatic nerve was detected by immunohistochemistry,and the expression of GAP-43 in L4-L6 spinal cord was detected by Western blotting.Results After 6 weeks,compared to the control group,the number of regenerated nerve fibers in the ursolic acid group increased,the arrangement was slightly regular,the capillary structure was abundant,and the proliferation of fibroblasts decreased;SFI and MNCV%were significantly increased(P<0.05),NGF protein positive expression was significantly increased(P<0.05),and the difference was statistically significant(P<0.05).GAP-43 protein expression in sciatic nerve tissue was significantly increased(P<0.05).Conclusions The intervention of ursolic acid extracted from Hippophae rhamnoides L.can improve the function of rats after sciatic nerve injury,promote the increase of regenerated nerve fibers and the repair of myelin sheath in rats with sciatic nerve injury,which may be related to increased NGF and GAP-43 protein expression in rats.
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ObjectiveTo observe the effects of fire-needle of Lingnan on the vitiligo model after hydroquinone-induced oxidative stress based on the Hippo-YAP signaling pathway. MethodsC57BL/6 mice were randomly divided into normal group （Control）， model group （HQ）， HQ+fire-needle group （FA）， and positive control group （Halometasone）， with 8 mice in each group. The vitiligo model was prepared by hydroquinone （HQ）. The skin pathological changes were observed by depigmentation score， HE staining and Masson-Fontana. Elisa was used to detect the levels of tyrosinase （TYR）， malondialdehyde （MDA） and monoamine oxidase （MAO）.Western-blot and PCR were used to detect the expression of Yap1 and Tp73 among the groups. ResultsCompared with the control group， the epidermis and dermis were significantly thicker. The number of melanocyte hair follicles， basal melanocytes， epidermal cells containing melanin granules were significantly decreased， and the depigmentation score was significantly reduced（P＜0.01）. The level of TYR decreased， and the levels of MDA and MAO increased after modeling（P＜0.01）. The expression of Yap1 and Tp73 were significantly reduced （P<0.01）. The dermis became thinner in the halometasone and FA group after treatment of 4 weeks. The number of melanocyte hair follicles， basal melanocytes， epidermal cells containing melanin granules increased （P<0.05）. Compared with that of the HQ group， the level of TYR in the halometasone group and FA group was significantly increased （P<0.01）. The levels of MDA and MAO in the FA group were decreased （P<0.05）. The expressions of Yap1 and Tp73 in the FA group were significantly increased （P<0.01）， and their effects were better than those in the Halometasone group （P<0.05）. ConclusionsFire-needle of Lingnan protects melanocytes from oxidative stress by activating the Hippo-YAP pathway. It enhances the synthesis and function of melanocytes and promotes repigmentation by reducing the content and activity of oxidative stress products.
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OBJECTIVE@#To investigate the effects of SINC, a secreted protein of Chlamydia psittaci, on autophagy of host cells and the role of MAPK/ERK signaling pathway in mediating SINC-induced autophagy.@*METHODS@#RAW 264.7 cells treated with recombinant SINC were examined for changes in expression levels of LC3-II, Beclin-1, phosphorylated and total ERK1/2 using Western blotting. The expression level of LC3 in the treated cells was detected using immunofluorescence analysis, and the formation of autophagosomes and autolysosomes was observed with transmission electron microscopy (TEM). The effect of pretreatment with U0126 (a specific ERK inhibitor) on the expression levels of LC3-II and Beclin-1 in RAW 264.7 cells exposed to different concentrations of SINC was examined using Western blotting, and LC3 puncta in the cells was detected with immunofluorescence analysis.@*RESULTS@#The expression levels of LC3-II and Beclin-1 were the highest in RAW 264.7 cells treated with 2 μg/mL SINC for 12h. Immunofluorescence analysis showed exposure to SINC significantly increased the number of cells containing LC3 puncta, where the presence of autophagosomes and autolysosomes was detected. Exposure to 2 μg/mL SINC for 15 min resulted in the most significant increase of the ratios of p-ERK1/2/ERK1/2 in RAW 264.7 cells. Pretreatment of the cells with U0126 prior to SINC exposure significantly decreased the ratio of p-ERK1/2/ERK1/2, lowered the expression levels of LC3-II and Beclin-1, and decreased LC3 aggregation in the cells.@*CONCLUSIONS@#SINC exposure can induce autophagy in RAW 264.7 cells by activating the MAPK/ERK signaling pathway.
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MAP Kinase Signaling System , Chlamydophila psittaci , Beclin-1 , Signal Transduction , AutophagyABSTRACT
ObjectiveIn view of the standardization of clinical diagnosis and treatment of the acute abdomen and the inheritance of diagnosis and treatment experience of prestigious veteran traditional Chinese medicine（TCM） doctors， a diagnosis and treatment reasoning algorithm based on association rule mining under incomplete evidence（AMIE）+ random walk was proposed to provide information services and technical support for primary doctors by recommending personalized diagnosis and treatment plans based on medical records. MethodThe experience of diagnosis and treatment of acute abdomen of prestigious veteran TCM doctors and the text data of clinical diagnosis and treatment guidelines of integrated TCM and western medicine were collected to complete the task of knowledge extraction and construct acute abdomen knowledge graph based on Neo4j. On the basis of ontology-supported rule-based reasoning， the rule reasoning based on similar syndromes was used to expand the syndrome combinations whose Jaccard similarity was greater than the threshold in the syndrome recommendation results. The semantic path coverage algorithm was used to calculate the semantic similarity between the symptom nodes. The symptom nodes were divided into 10 categories， and the symptom nodes in the same category were extended. The random walk algorithm was used to search the symptom nodes connected with the syndrome， and the connection rules between the syndrome and symptom nodes were extended to realize the knowledge reasoning of AMIE+ random walk. ResultThe acute abdomen knowledge graph included 1 320 nodes and 2 464 relationships. According to the link prediction evaluation index of knowledge reasoning， the reasoning results of the three algorithms in the auxiliary diagnosis and treatment of acute abdomen were compared. The AMIE+ random walk algorithm complemented the knowledge graph by extending the similar syndrome connection rules and the syndrome-symptom connection rules. Compared with the knowledge reasoning algorithm based on ontology rules， the area under the curve （AUC） was 15.18% higher and the accuracy was 30.36% higher， which achieved more accurate and effective knowledge inference. ConclusionThis study used knowledge graph technology to visualize the diagnosis and treatment of acute abdomen with TCM and western medicine， assisting primary clinicians in intuitively viewing the diagnosis and treatment process and data relationship. The proposed diagnosis and treatment reasoning algorithm can realize the personalized diagnosis and treatment plan recommendation at the level of "disease-syndrome-diagnosis-treatment-prescription"， which can assist primary doctors in disease diagnosis and treatment and clinical decision-making， contribute to the knowledge sharing and application of diagnosis and treatment experience and clinical guidelines of prestigious veteran TCM doctors， improve the level of primary clinical diagnosis and treatment， and promote the normalization and standardization of the diagnosis and treatment process of acute abdomen with integrated TCM and western medicine.
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OBJECTIVE@#To observe the impacts of acupuncture on depressive mood and sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia, and explore its effect mechanism.@*METHODS@#A total of 60 patients with comorbid mild-to-moderate depressive disorder and insomnia were randomly divided into an observation group (30 cases, 1 case dropped off) and a control group (30 cases, 2 cases dropped off). In the observation group, acupuncture and low frequency repeated transcranial magnetic stimulation (rTMS) were combined for the intervention. Acupuncture was applied to Baihui (GV 20), Yintang (GV 24+), Neiguan (PC 6) and Yanglingquan (GB 34), etc., the needles were retained for 30 min; and the intradermal needles were embedded at Xinshu (BL 15) and Danshu (BL 19) for 2 days. After acupuncture, the rTMS was delivered at the right dorsolateral prefrontal cortex (R-DLPFC), with 1 Hz and 80% of movement threshold, lasting 30 min in each treatment. In the control group, the sham-acupuncture was adopted, combined with low frequency rTMS. The acupoint selection and manipulation were the same as the observation group. In the two groups, acupuncture was given once every two days, 3 times weekly; while, rTMS was operated once daily, for consecutive 5 days a week. The duration of treatment consisted of 4 weeks. Hamilton depression scale-17 (HAMD-17) and Pittsburgh sleep quality index (PSQI) scores were observed before and after treatment, as well as 1 month after the treatment completion (follow-up period) separately. Besides, the levels of nerve growth factor (BDNF) and γ-aminobutyric acid (GABA) in the serum were detected before and after treatment in the two groups.@*RESULTS@#After treatment and in follow-up, the HAMD-17 scores were lower than those before treatment in the two groups (P<0.05), and the scores in the observation group were lower than the control group (P<0.05). After treatment, the total scores and the scores of each factor of PSQI were reduced in the two groups in comparison with those before treatment except for the score of sleep efficiency in the control group (P<0.05); the total PSQI score and the scores for sleep quality, sleep latency, sleep efficiency and daytime dysfunction in the observation group were all lower than those in the control group (P<0.05). In the follow-up, except for the scores of sleep duration and sleep efficiency in the control group, the total PSQI score and the scores of all the other factors were reduced compared with those before treatment in the two groups (P<0.05); the total PSQI score and the scores of sleep quality, sleep latency, sleep duration, sleep efficiency and daytime dysfunction in the observation group were lower than the control group (P<0.05). After treatment, the levels of serum BDNF and GABA were increased in comparison with those before treatment in the observation group (P<0.05), and the level of serum BDNF was higher than that in the control group (P<0.05).@*CONCLUSION@#Acupuncture relieves depressive mood and improves sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia. The effect mechanism may be related to the regulation of BDNF and GABA levels and the promotion of brain neurological function recovery.