Revision surgery for periprosthetic fracture of distal femur after endoprosthetic replacement of knee joint following resection of osteosarcoma.

Purpose: Periprosthetic fracture (PPF) is one of the severe complications in patients with osteosarcoma and carries the risk of limb loss. This study describes the characteristics, treatment strategies, and outcomes of this complication. Methods: Patients were consecutively included who were treated at our institution between 2016 and 2020 with a PPF of distal femur. The treatment strategies included two types: 1) open reduction and internal fixation with plates and screws and 2) replacement with long-stem endoprosthesis and reinforcement with wire rope if necessary. Results: A total of 11 patients (mean age 12.2 years (9-14)) were included, and the mean follow-up period was 36.5 (21-54) months. Most fractures were caused by direct or indirect trauma (n = 8), and others (n = 3) underwent PPF without obvious cause. The first type of treatment was performed on four patients, and the second type was performed on seven patients. The mean Musculoskeletal Tumor Society (MSTS) score was 20 (17-23). All patients recovered from the complication, and limb preservation could be achieved. Conclusion: PPF is a big challenge for musculoskeletal oncologists, particularly in younger patients. Additionally, PPF poses a challenge for orthopedic surgeons, as limb preservation should be an important goal. Hence, internal fixation with plates and endoprosthetic replacement are optional treatment strategies based on fracture type and patient needs.

Benzo(a)pyrene promotes the malignant progression of malignant-transformed BEAS-2B cells by regulating YTH N6-methyladenosine RNA binding protein 1 to inhibit ferroptosis.

Benzo[a]pyrene (BaP) is associated with the development of lung cancer, but the underlying mechanism has not been completely clarified. Here, we used 10 µM BaP to induce malignant transformation of human bronchial epithelial BEAS-2B cells, named BEAS-2B-T. Results indicated that BaP (6.25, 12.5 and 25 µM) treatment significantly promoted the migration and invasion of BEAS-2B-T cells. Meanwhile, BaP exposure inhibited ferroptosis in BEAS-2B-T, ferroptosis-related indexes Fe2+, malondialdehyde (MDA), lipid peroxidation (LPO) and reactive oxygen species (ROS) decreased significantly. The protein level of ferroptosis-related molecule transferrin receptor (TFRC) decreased significantly, while solute carrier family 7 membrane 11 (SLC7A11), ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4 (GPX4) increased significantly. The intervention of ferroptosis dramatically effected the migration and invasion of BEAS-2B-T induced by BaP. Furthermore, the expression of YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) was markedly increased after BaP exposure. YTHDF1 knockdown inhibited BEAS-2B-T migration and invasion by promoting ferroptosis. In the meantime, the contents of Fe2+, MDA, LPO and ROS increased significantly, TFRC was markedly increased, and SLC7A11, FTH1, and GPX4 were markedly decreased. Moreover, overexpression of YTHDF1 promoted BEAS-2B-T migration and invasion by inhibiting ferroptosis. Importantly, knockdown of YTHDF1 promoted ferroptosis and reduced BEAS-2B-T migration and invasion during BaP exposure, and overexpression of YTHDF1 increased migration and invasion of BEAS-2B-T by inhibiting ferroptosis during BaP exposure. RNA immunoprecipitation assays indicated that the binding of YTHDF1 to SLC7A11 and FTH1 markedly increased after YTHDF1 overexpression. Therefore, we concluded that BaP promotes the malignant progression of BEAS-2B-T cells through YTHDF1 upregulating SLC7A11 and FTH1 to inhibit ferroptosis. This study reveals new epigenetic and ferroptosis markers for preventing and treating lung cancer induced by environmental carcinogens.

Genetic diagnosis,observation of sperm ultrastructure and outcome analysis for assisted reproduction in Hui and Uyghur pa-tients with globozoospermia / 临床检验杂志

Objective To investigate the clinical phenotype,sperm characteristics,genetic etiology and the outcomes of assisted repro-ductive technology of 2 minority patients(P1 Hui and P2 Uyghur)with globozoospermia.Methods The clinical data and various pa-rameters of semen examination in the 2 minority patients with globozoospermia were analyzed.The ultrastructure of their sperms was ob-served,and the genetic etiology of the patients was analyzed by whole exome sequencing(WES)and qPCR.Intracytoplasmic sperm in-jection(ICSI)combined with artificial oocyte activation(AOA)were applied for assisted reproduction thyrapy.The outcomes of assis-ted reproduction in the two couples were observed.Results Homozygous 109681 bp deletion in DPY19L2 gene was found in both the patients.The homozygous deletion of DPY19L2 gene in P2 patient came from his inbred parents.Low sperm motility and high sperm DNA fragmentation rate were observed in the P1 patient,the and the rate of round-headed sperm was 100％in morphology.The ab-sence of sperm acrosome and ultrastructural defects of plasma membrane,mitochondria and microtubules were found under the electron microscope.In the P2 patient,sperm motility and sperm DNA fragmentation rate patient were normal,and the sperm morphology was 100％round-headed sperm.Under the electron microscope,the main defects of sperm were small and round head with acrosomal ab-sence,structural damage,but the ultrastructural defects of organelles were rare,such as plasma membrane,mitochondria and microtu-bules.Both couples of the two patients received ICSI+AOA for assisted pregnancy,and the ICSI fertilization rate was 62.5％for P1 pa-tient and 75％for P2 patient.Both the patients successfully obtained clinical pregnancy.Conclusion The abnormal DPY19L2 gene is the main genetic cause in the globozoospermia patients with different ethnic backgrounds.Both structural damage and ultrastructural de-fects of organelles such as plasma membrane,mitochondrial and microtubule damage could be found in globozoospermia.ICSI combined with AOA should be an effective assisted reproductive thyrapy strategy for the patients with globozoospermia.

Effect of Danggui Niantongtang on Intestinal Flora of Knee Osteoarthritis Mice Based on 16S rDNA Sequencing / 中国实验方剂学杂志

ObjectiveThis study aims to explore the potential mechanism of Danggui Niantongtang in treating knee osteoarthritis （KOA） by regulating the intestinal flora through 16S rDNA analysis. MethodThirty-six C57BL/6J mice were subjected to anterior cruciate ligament transection （ACLT） to establish a KOA model and were randomly divided into the sham surgery group， model group， low-dose Danggui Niantongtang group （0.819 g·kg-1）， medium-dose Danggui Niantongtang group （1.638 g·kg-1）， high-dose Danggui Niantongtang group （3.276 g·kg-1）， and Meloxicam group （0.975 mg·kg-1）， with 6 mice in each group. Except for the treatment groups， the sham surgery group and model group were given normal saline by gavage. After 4 weeks of continuous intervention， feces and intact knee joints of the mice were collected. Hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining were performed to observe the pathological changes in knee joint tissue morphology. The 16S rDNA sequencing was used to analyze changes in the abundance and diversity of intestinal microorganisms before and after treatment， along with corresponding functional predictions. ResultHigh-dose Danggui Niantongtang and Meloxicam significantly relieved pain symptoms in KOA mice， improved the disorder of joint structure， maintained the integrity of knee articular cartilage， increased the expression of type Ⅱ collagen alpha 1 （Col2a1） in articular cartilage， and decreased the expression of matrix metalloproteinase-13 （MMP-13）. The results of 16S rDNA sequencing showed that high-dose Danggui Niantongtang could adjust the abundance and structure of intestinal microbial species. Compared with the sham surgery group， the abundance of Proteobacteria， Actinobacteria， Ruminococcus， and Bacteroides was significantly increased in the model group （P<0.05）， while in the Danggui Niantongtang group， the abundance of these four flora was significantly reduced compared with the model group. Compared with the sham surgery group， the abundance of Verrucomicrobia， Oscillospira， and Akkermansia was significantly decreased in the model group （P<0.05）， while in the Danggui Niantongtang groups， the abundance of these three flora was significantly increased compared with the model group （P<0.05）. Functional pathway prediction of differential genera revealed that species differences among groups mainly involved metabolic pathways with high abundance associated with biosynthesis and precursors， as well as energy production， including amino acid biosynthesis， nucleotide and nucleoside biosynthesis， cofactors， prosthetic groups， electron carriers， and vitamin biosynthesis. ConclusionDanggui Niantongtang can effectively protect articular cartilage and delay the progression of KOA， possibly by regulating the structure of the intestinal flora， promoting probiotics， and inhibiting the growth of harmful pathogenic bacteria.

Clinical Effectiveness and Safety of Bairui Granules （百蕊颗粒） in Treating Patients with Acute Pharyngitis with Wind-Heat Syndrome： A Multi-Center， Double-Blind， Double-Simulation， Randomized Controlled Trial / 中医杂志

ObjectiveTo evaluate the clinical effectiveness and safety of Bairui Granules （百蕊颗粒） in the treatment of acute pharyngitis with wind-heat syndrome. MethodsA multicenter， double-blind， double-simulation， randomised controlled trial was conducted， in which 162 patients with acute pharyngitis and wind-heat syndrome from 7 centers were recruited， and each center was divided into trial group and control group on the ratio of 2∶1. In the trial group， 108 cases were orally administered with Bairui Granules plus Reyanning Granules （热炎宁颗粒） simulant， and in the control group， 54 cases were orally administered with Reyanning Granules plus Bairui Granules simulant for 5 days， with a follow-up visit on the 6th day. Full analysis set （FAS） analysis and per protocol set （PPS） were used for analysis， respectively. The primary efficacy index was the disappearance rate of sore throat after 5-day treatment； the secondary efficacy indexes were the disappearance rate of sore throat after 3-day treatment， as well as the visual analogue score （VAS） of sore throat before treatment， every day during the treatment， and follow-up on day 6， and the traditional Chinese medicine （TCM） syndrome score was performed before treatment and at the follow-up on day 6. The effectiveness on TCM syndrome was evaluated at the follow-up on day 6， and the changes of vital signs， blood routine， urine routine， liver functions， kidney function， the adverse events before and after the treatment were recorded， and safety analysis set （SS） was analysed. Results162 patients entered the FAS and SS analyses， and 158 cases （105 cases in the trial group and 53 cases in the control group） entered the PPS analysis. FAS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.56% （87/108） in the trial group and 64.81% （35/54） in the control group， and the difference between groups was statistically significant （χ2 = 5.10， P = 0.0239）. PPS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.00% （84/105） in the trial group and 64.15% （34/53） in the control group， and the difference between groups was statistically significant （χ2 =4.85， P = 0.0277）. FAS and SS analyses both showed that the difference in disappearance rate of sore throat between groups on 3-day treatment was not statistically significant （P＞0.05）. Compared with those before treatment， the VAS scores of sore throat were lower in both groups during treatment on day 2， 3， 4， 5， and follow-up on day 6 （P＜0.01）， but the difference between groups at each time point was not statistically significant （P＞0.05）. TCM syndrome scores of both groups at the follow-up were lower than that before treatment， and those of the trial group were lower than those of the control group （P＜0.01）. The cure rate and effective rate of TCM syndrome of the trial group were significantly higher than those of the control group （P＜0.01）. There was no significant difference in blood routine， urine routine， liver function， kidney function between groups before and after treatment （P＞0.05）， and no serious adverse events occured in both groups. ConclusionBairui Granules showed clinical effectiveness in the treatment of acute pharyngitis of wind-heat syndrome， and it could significantly improve the clinical symptoms， accelerate the disappearance time of sore throat with good safety.

Application of self-made "medical ventilation chair" in patients with acute respiratory distress syndrome in prone position / 中国实用护理杂志

Objective:To investigate the effect of self-made medical ventilation chair in patients with acute respiratory distress syndrome (ARDS) ventilated in prone position, with the aim of reducing the occurrence of complications in patients with ARDS ventilated in prone position.Methods:This study was a quasi experimental research method. In this study, 78 patients admitted to the respiratory intensive care unit of Changsha Central Hospital affiliated to South China University from October 2019 to September 2021 were selected for the study by convenience sampling method, and were divided into a control group and a experimental group according to the order of admission, with 39 cases in each group. The experimental group was ventilated in the prone position using a self-made medical ventilation chair, and the control group was ventilated in the prone position using the conventional turning method, comparing the facial skin injury, tracheal displacement, tracheal tube obstruction, and RICU hospitalization time in the two groups.Results:At the end of prone position ventilation, the incidence of facial skin intact and redness and swelling was 56.41% (22/39) and 43.59% (17/39) in the experimental group and 25.64% (10/39) and 69.23% (27/39) in the control group, respectively, with statistically significant differences ( χ2=7.63, 5.21, both P<0.05); there was no statistically significant difference in the incidence of facial skin breakdown between the two groups ( P>0.05); the incidence of complications was 5.13% (2/39) in the experimental group and 20.51% (8/39) in the control group, with statistically significant differences ( χ2=4.13, P<0.05); the duration of RICU stay was (13.34 ± 3.85) days in the experimental group and ( 15.80 ± 5.55) days, with a statistically significant difference ( t=2.25, P<0.05). Conclusions:The use of self-made medical ventilation chair can reduce the facial skin damage of patients, reduce the occurrence of related complications, and shorten the hospitalization time of RICU. It is worth popularizing and applying in ICU.

A comparative study of absorbable screw fixation and absorbable screw combined with suture anchor fixation in treatment of avulsion fracture of posterior cruciate ligament at tibial insertion of knee joint / 中国修复重建外科杂志

OBJECTIVE@#To compare the effectiveness of open reduction of posterior cruciate ligament (PCL) avulsion fracture at tibial insertion of knee joint with absorbable screws fixation and absorbable screw combined with suture anchor fixation.@*METHODS@#The clinical data of 26 patients with PCL avulsion fracture at tibial insertion who met the selection criteria between March 2015 and October 2021 were retrospectively analyzed. Among them, 14 patients were fixed with simple absorbable screw (group A), and 12 patients were fixed with absorbable screw combined with suture anchors (group B). All patients were confirmed by X-ray film, CT, or MRI preoperatively, and got positive results in preoperative posterior drawer tests. There was no significant difference in gender, age, side of affected limb, time from injury to operation, comorbidities, and preoperative Meyers & McKeever classification, Lysholm score, and International Knee Documentation Committee (IKDC) score between the two groups ( P>0.05). The operation time and postoperative complications were recorded and compared between the two groups. At last follow-up, Lysholm score and IKDC score were used to evaluate the improvement of knee function.@*RESULTS@#There was no significant difference in operation time between the two groups ( P>0.05). All incisions healed by first intention, and no complication such as vascular and nerve injury or venous thrombosis occurred. All 26 patients were followed up 9-89 months, with an average of 55.3 months. The follow-up time of group A and group B was (55.7±23.2) and (56.8±29.3) months, respectively, with no significant difference ( t=-0.106, P=0.916). Radiographs showed bone healing in both groups at 3 months after operation, and no complication such as infection and traumatic arthritis occurred. At last follow-up, the posterior drawer test was negative in both groups, and the Lysholm score and IKDC score significantly improved when compared with the pre-operative values ( P<0.05). However, there was no significant difference in the improvement value between the two groups ( P>0.05).@*CONCLUSION@#For PCL avulsion fracture at tibial insertion of the knee joint, the open reduction and absorbable screw combined with suture anchor fixation can achieve reliable fracture reduction and fixation, which is conducive to the early rehabilitation and functional exercise, and the postoperative functional recovery of the knee joint is satisfactory.

Expression and clinical value of miR-21 in septic acute respiratory distress syndrome / 中华急诊医学杂志

Objective:To investigate the expression level of miR-21 in patients with septic acute respiratory distress syndrome, and analyze its correlation with inflammatory factors and its value in evaluating clinical prognosis.Methods:Patients with sepsis admitted to the intensive care unit (ICU) of the First Affiliated Hospital of Hebei North University from October 2020 to March 2022 were prospectively recruited. The patients were divided into an ARDS group and a non-ARDS group according to whether ARDS occurred within 3 days after admission. The ARDS group was divided into a low-risk group and a high-risk group according to the oxygenation index, and the ARDS group was divided into a survival group and a death group according to their 28-day survival status. In addition, 50 healthy volunteers who underwent physical examination during the same period were included in the control group. The expression levels of serum miR-21 and inflammatory factors [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] were compared in each group at admission. To analyze the relationship between miR-21 expression and inflammatory factors and explore the value of miR-21 in predicting the prognosis of sepsis patients with ARDS.Results:A total of 106 patients with sepsis were included. Compared with the healthy control group, the levels of serum miR-21, TNF-α and IL-6 in the ARDS group and non-ARDS group were significantly increased (all P<0.05). Compared with the low-risk group, the levels of serum miR-21, TNF-α and IL-6 in the high-risk group were significantly increased (all P<0.05). Compared with the survival group, the serum miR-21 expression level and TNF-α and IL-6 levels in the death group were significantly increased (all P<0.05). Pearson correlation analysis showed that the serum miR-21 expression level in the ARDS group was positively correlated with IL-6 and TNF-α levels ( r=0.842, 0.697, P<0.001). ROC curve analysis showed that the AUC of serum miR-21 in predicting death from sepsis complicated with ARDS was 0.876 (95% CI: 0.761-0.942), the best cut-off value was 2.25, and its sensitivity and specificity were 92.9% and 71.7%, respectively. Conclusions:The expression level of serum miR-21 is significantly increased in patients with sepsis ARDS, is positively correlated with the level of inflammatory factors, is closely correlated with the severity and prognosis of the disease, and has great value in evaluating the prognosis of patients with sepsis ARDS.

Lipid nanoparticle delivery of siRNA targeting Cyp2e1 gene attenuates subacute alcoholic liver injury in mice / 浙江大学学报·医学版

OBJECTIVES@#To investigate the effect and mechanism of lipid nanoparticle (LNP) delivery of small interfering RNA (siRNA) targeting Cyp2e1 gene on subacute alcoholic liver injury in mice.@*METHODS@#siRNA targeting Cyp2e1 gene was encapsulated in LNP (si-Cyp2e1 LNP) by microfluidic technique and the resulting LNPs were characterized. The optimal dose of si-Cyp2e1 LNP administration was screened. Forty female C57BL/6N mice were randomly divided into blank control group, model control group, si-Cyp2e1 LNP group, LNP control group and metadoxine group. The subacute alcoholic liver injury mouse model was induced by ethanol feeding for 10 d plus ethanol gavage for the last 3 d. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and the superoxide dismutase (SOD) activity as well as malondialdehyde, reactive oxygen species, glutathione, triacylglycerol, total cholesterol contents in liver tissue were measured in each group, and liver index was calculated. The expression of genes related to oxidative stress, lipid synthesis and inflammation in each group of mice were measured by realtime RT-PCR.@*RESULTS@#Compared with the model control group, the levels of liver index, serum ALT, AST activities, malondialdehyde, reactive oxygen species, triacylglycerol, total cholesterol contents in liver tissue decreased, but the SOD activity as well as glutathione increased in the si-Cyp2e1 LNP group (all P<0.01). Hematoxylin-eosin staining result showed disorganized hepatocytes with sparse cytoplasm and a large number of fat vacuoles and necrosis in the model control group, while the si-Cyp2e1 LNP group had uniformly sized and arranged hepatocytes with normal liver tissue morphology and structure. Oil red O staining result showed si-Cyp2e1 LNP group had lower fat content of the liver compared to the model control group (P<0.01), and no fat droplets accumulated. Anti-F4/80 monoclonal antibody fluorescence immunohistochemistry showed that the si-Cyp2e1 LNP group had lower cumulative optical density values compared to the model control group (P<0.01) and no significant inflammatory reaction. Compared with the model control group, the expression of catalytic genes P47phox, P67phox and Gp91phox were reduced (all P<0.01), while the expression of the antioxidant enzyme genes Sod1, Gsh-rd and Gsh-px were increased (all P<0.01). The mRNA expression of the lipid metabolism genes Pgc-1α and Cpt1 were increased (all P<0.01) and the lipid synthesis-related genes Srebp1c, Acc and Fasn were decreased (all P<0.01); the expression of liver inflammation-related genes Tgf-β, Tnf-α and Il-6 were decreased (all P<0.01).@*CONCLUSIONS@#The si-Cyp2e1 LNP may attenuate subacute alcoholic liver injury in mice mainly by reducing reactive oxygen levels, increasing antioxidant activity, blocking oxidative stress pathways and reducing ethanol-induced steatosis and inflammation.

JAK2/STAT3 Signaling Pathway Mechanism of Electroacupuncture in Reducing Inflammatory Response to Myocardial Ischemia-Reperfusion Injury / 世界科学技术-中医药现代化

Objective To observe the expression of tyrosine kinase 2(JAK2)and signal transducer and activator of transcription 3(STAT3)in myocardial tissue of rats with myocardial ischemia-reperfusion injury(MIRI)by electroacupuncture at"Neiguan"point,and explore the mechanism of electroacupuncture in up regulating JAK2/STAT3 signal pathway,promoting the expression of anti-inflammatory factors,and reducing MIRI injury.Methods Thirty male SD rats with normal echocardiography were randomly divided into sham operation group,model group and electroacupuncture group,with 10 rats in each group.MIRI models were prepared by ligation of left anterior descending coronary artery(LAD)in model group and electroacupuncture group,while in sham operation group,only threading was performed without ligation.In the electroacupuncture group,electroacupuncture(density wave,2 Hz/100 Hz,2 mA)at bilateral"Neiguan"points was performed on the 1st,3rd and 5th days after the modeling operation,once a day,20 minutes each time.The left ventricular ejection fraction(LVEF)of rats on the 1st,3rd and 5th day after operation was observed by echocardiography to evaluate cardiac function;HE staining was used to observe the pathological changes of rat myocardium;The myocardial fibrosis was observed by Masson staining;The expression of IL-4 and IL-6 in myocardium was detected by ELISA;The expressions of IL-1β and IL-10 in myocardial tissue were detected by immunohistochemistry;The expression of JAK2,p-JAK2,STAT3,p-STAT3 protein in myocardial infarction area was measured by Western blot.Results Compared with sham operation group,EF in model group decreased significantly(P<0.05),fibrosis area increased(P<0.05),IL-4,IL-6,IL-10,IL-1β The content of JAK2,p-JAK2,STAT3,p-STAT3 protein increased(P<0.05);Compared with the model group,the EF of rats in the electroacupuncture group increased(P<0.05),the fibrotic area of rats in the electroacupuncture group decreased(P<0.05),the content of IL-4 and IL-10 increased,and IL-6 and IL-1β The expression of JAK2,p-JAK2,STAT3,p-STAT3 protein increased(P<0.05).Conclusion Electroacupuncture at Neiguan point can significantly up regulate JAK2/STAT3 signal pathway,reduce the secretion of proinflammatory factors,increase the expression of anti-inflammatory factors,and alleviate myocardial ischemia reperfusion injury in rats.

Pharmacodynamic substances and mechanism of Chelidonii Herba-Corydalis Rhizoma against estrogen receptor-positive breast cancer / 中国药房

OBJECTIVE To analyze the main components of Chelidonii Herba-Corydalis Rhizoma （CHCR）， and to predict pharmacodynamic substances against estrogen receptor （ER） -positive breast cancer and their potential targets and signaling pathways， followed by verifying experiments. METHODS The ethanol extract of CHCR was analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS/MS）. The network pharmacology analysis was performed for the screened components. The network diagram of CHCR “active components-target-pathway” was constructed， and the enrichment pathway in vitro was validated. RESULTS A total of 58 chemical components were identified， including 57 alkaloids and 1 organic acid. A total of 38 active ingredients were screened from the network pharmacology， and 38 core targets were found in the protein-protein interaction network of “component-disease” intersection targets； 258 gene ontology entries and 137 Kyoto encyclopedia of genes and genomics pathways were obtained， mainly including estrogen signal pathway， phosphatidylinositol-3-kinase/protein kinase B （PI3K/Akt） signal pathway， etc. The results of validation test showed that the median inhibitory concentration of CHCR to MCF-7 cells was 693 μg/mL； 150， 300， 600 μg/mL CHCR could significantly reduce the expressions of phosphorylated PI3K， phosphorylated Akt， ERα protein and ESR1 mRNA （P＜0.01）. CONCLUSIONS The anti-ER-positive breast cancer effect of CHCR may be related to the regulation of ER and PI3K/Akt pathways， which has the characteristics of multi-component and multi-target effects.

Amelioration of ethanol-induced oxidative stress and alcoholic liver disease by in vivo RNAi targeting Cyp2e1

Alcoholic liver disease (ALD) results from continuous and heavy alcohol consumption. The current treatment strategy for ALD is based on alcohol withdrawal coupled with antioxidant drug intervention, which is a long process with poor efficacy and low patient compliance. Alcohol-induced CYP2E1 upregulation has been demonstrated as a key regulator of ALD, but CYP2E1 knockdown in humans was impractical, and pharmacological inhibition of CYP2E1 by a clinically relevant approach for treating ALD was not shown. In this study, we developed a RNAi therapeutics delivered by lipid nanoparticle, and treated mice fed on Lieber-DeCarli ethanol liquid diet weekly for up to 12 weeks. This RNAi-based inhibition of Cyp2e1 expression reduced reactive oxygen species and oxidative stress in mouse livers, and contributed to improved ALD symptoms in mice. The liver fat accumulation, hepatocyte inflammation, and fibrosis were reduced in ALD models. Therefore, this study suggested the feasibility of RNAi targeting to CYP2E1 as a potential therapeutic tool to the development of ALD.

Effect of electroacupuncture on myocardial fibrosis in spontaneously hypertensive rats based on cholinergic anti-inflammatory pathway / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on myocardial fibrosis in spontaneously hypertensive rats (SHR), and explore preliminarily the mediating role of cholinergic anti-inflammatory pathway (CAP) and its downstream nuclear factor κB (NF-κB) signaling pathway.@*METHODS@#Six 12-week-old WKY male rats were employed as the normal group. Eighteen 12-week-old SHR were randomly divided into 3 groups, i.e. a model group, an EA group and a blocking group (EA after blocking α7 nicotinic acetylcholine receptor [α7nAchR]), with 6 rats in each one. In the EA group, EA was delivered at "Neiguan"(PC 6) and the site 0.5 cm from its left side, with disperse-dense wave, 2 Hz/15 Hz in frequency and 1 mA in current intensity. One intervention took 30 min and was given once every 2 days, lasting 8 weeks. In the blocking group, prior to each EA, the α7nAchR specific blocker, α-bungartoxin was injected intravenously in the tails of the rats. After EA intervention, the systolic blood pressure (SBP), the diastolic blood pressure (DBP) and the mean arterial pressure (MAP) were measured with non-invasive blood pressure monitor. Using echocardiogram, the left ventricular (LV) anterior wall end-diastolic thickness (LVAWd) , LV posterior wall end-diastolic thickness (LVPWd) and the LV end-diastolic internal diameter (LVIDd) were measured. The level of hydroxyproline (Hyp) in the myocardial tissue was determined by using alkaline hydrolysis, and that of acetylcholine (Ach) was detected by ELISA. With the real-time PCR adopted, the mRNA expression of NF-κB p65, tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 were determined.@*RESULTS@#Compared with the normal group, SBP, DBP, MAP, LVAWd and LVPWd were increased (P<0.01), and LVIDd was decreased (P<0.01) in the rats of the model group. SBP, DBP, MAP and LVAWd were dropped (P<0.01, P<0.05), and LVIDd rose (P<0.01) in the EA group when compared with those in the model group. The differences in the above indexes were not statistically significant between the blocking group and the model group (P>0.05). Compared with the normal group, Hyp level and the mRNA expression of NF-κB p65, TNF-α, IL-1β and IL-6 in the myocardial tissue increased (P<0.01, P<0.05) and Ach level decreased (P<0.01) in the model group. Hyp level, the mRNA expression of NF-κB p65, TNF-α, IL-1β and IL-6 in the myocardial tissue were reduced (P<0.05, P<0.01) and Ach level rose (P<0.01) in the EA group when compared with those in the model group. These indexes were not different statistically between the blocking group and the model group (P>0.05).@*CONCLUSION@#CAP may be involved in ameliorating the pathological damage of myocardial fibrosis during EA at "Neiguan"(PC 6). The underlying effect mechanism is associated with up-regulating the neurotransmitter, Ach and down-regulating mRNA expression of NF-κB p65 and pro-inflammatory factors such as TNF-α, IL-1β and IL-6 in myocardial tissue.

Genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021 / 中华预防医学杂志

Objective: To characterize the prevalence and genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021. Methods: Based on the Shenzhen Infectious Diarrhea Surveillance System, acute diarrheal patients were actively monitored in sentinel hospitals from 2013 to 2021. Whole-genome sequencing (WGS) of Vibrio parahaemolyticus isolates was performed, and the genomic population structure, serotypes, virulence genes and multilocus sequence typing were analyzed. Outbreak clusters from 2019 to 2021 were explored based on single-nucleotide polymorphism analysis. Results: A total of 48 623 acute diarrhea cases were monitored in 15 sentinel hospitals from 2013 to 2021, and 1 135 Vibrio parahaemolyticus strains were isolated, with a positive isolation rate of 2.3%. Qualified whole-genome sequencing data of 852 isolates were obtained. Eighty-nine serotypes, 21 known ST types and 5 new ST types were identified by sequence analysis, and 93.2% of strains were detected with toxin profile of tdh+trh-. 8 clonal groups (CGs) were captured, with CG3 as the absolute predominance, followed by CG189. The CG3 group was dominated by O3:K6 serotype and ST3 sequence type, while CG189 group was mainly O4:KUT, O4:K8 serotypes and ST189a and ST189 type. A total of 13 clusters were identified, containing 154 cases. About 30 outbreak clusters with 29 outbreak clusters caused by CG3 strains from 2019 to 2021. Conclusion: Vibrio parahaemolyticus is a major pathogen of acute infectious diarrhea in Shenzhen City, with diverse population structures. CG3 and CG189 have been prevalent and predominant in Shenzhen City for a long time. Scattered outbreaks and persistent sources of contamination ignored by traditional methods could be captured by WGS analysis. Tracing the source of epidemic clone groups and taking precise prevention and control measures are expected to significantly reduce the burden of diarrhea diseases caused by Vibrio parahaemolyticus infection in Shenzhen City.

Construction and application of "Five-in-one" blended teaching model in the course of fundamental nursing / 中华医学教育探索杂志

Objective:To construct a "Five-in-one" blended teaching model in the course of fundamental nursing with ideological and political education as the core, integrated with online and offline, and complemented with theory and experiment, and to explore its application effect.Methods:Eight classes of nursing undergraduates in Batch 2019 were selected through convenience sampling method, and through random cluster sampling, Class 5 to 8 were divided into control group and Class 1 to 4 were divided into experimental group. The control group used the traditional teaching method, the experimental group used the "Five-in-one" mixed teaching model. After the course, the teaching effect was evaluated by the professional commitment scale, the recessive truancy scale for college students, the self-regulated learning ability scale and the examination results. SPSS 23.0 software was used for t test. Results:After teaching, the scores of professional commitment, self-adjustment in recessive truancy, autonomous learning ability and examination results of the experimental group were higher than those of the control group [(91.30±10.38) vs. (87.31±16.40), (23.30±4.50) vs. (21.23±4.51), (82.31±10.06) vs. (79.42±9.79), (72.31±10.13) vs. (70.14±9.67) and (87.93±4.60) vs. (86.50±4.67), respectively]. The scores of academic cognition, learning habit, classroom cognition and learning environment in recessive truancy of the experimental group were lower than those in control group, with statistical significance.Conclusion:The application of "Five-in-one" blended teaching model in the course of fundamental nursing can reduce students' recessive truancy and improve their professional commitment, autonomous learning ability and academic achievement.

Genetic analysis of a Chinese pedigree affected with branchiootic syndrome due to a nonsense variant of EYA1 gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotype and genetic basis for a Chinese pedigree suspected for branchiootic syndrome (BOS).@*METHODS@#The proband was subjected to target-capture high-throughput sequencing to detect potential variant of deafness-associated genes. Candidate variants were verified by Sanger sequencing of the family members.@*RESULTS@#The proband was found to harbor a c.1627C>T (p.Gln543Ter) nonsense variant of the EYA1 gene. Sanger sequencing confirmed that all of the 4 patients with the BOS phenotype from the pedigree have harbored the same heterozygous variant. Based on the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic (PVS1+PS+PP3+PP4).@*CONCLUSION@#The c.1627C>T (p.Gln543Ter) variant of the EYA1 gene probably underlay the BOS phenotype in this pedigree. Above finding has provided a basis for its clinical diagnosis.

Genipin Protects High Glucose-injured MIN6 Cells / 中国生物化学与分子生物学报

Genipin (Gen) is an important antioxidant that plays a crucial role in the process of intracellular resistance to oxidative stress. In order to study the effect of genipin on MIN6 cells injured by high glucose, the CCK-8 method was used to detect the cell survival rate. The cell viability of the high-glucose injury group decreased (P <0. 05). But after genipin acted on the cells injured by high glucose, the cell viability increased (P <0. 05). The mouse insulin detection kit and ATP content detection kit found that the insulin release in the high glucose injury group decreased (P < 0. 001) and the ATP content decreased (P <0. 001). After genipin was given, the insulin release increased (P <0. 01), ATP content increased (P <0. 01). The fluorescent probe DCFH-DA detected the intracellular reactive oxygen species (ROS) level and found that the ROS content in the high glucose-injury group was significantly increased (P <0. 01). After genipin was administered, ROS content decreased (P < 0. 05). Glutathione(GSH) / oxidized glutathione (GSSG), intracellular malondialdehyde (MDA), superoxide dismutase(SOD) and catalase (CAT) and lactate dehydrogenase (LDH) activity in the cell supernatant revealed that the GSH / GSSH ratio, SOD and CAT levels in the high glucose injury group decreased (P <0. 05), and the intracellular MDA and LDH levels were significant increased (P<0. 001) .After administration of genipin, the GSH / GSSH ratio, SOD and CAT levels increased (P <0. 01), MDA and LDH levels were significantly reduced (P <0. 01). Mitochondrial membrane potential (MMP) levels decreased in the highglucose injury group (P <0. 01). After genipin acted on the cells injured by high glucose, the MMP level increased (P < 0. 05). Western blot detected uncoupling protein 2 (UCP2), antioxidative proteinsglutathione reductase (GR) and glutaredoxin 1 (Grx1) contents. The results showed that UCP2 contents in the high glucose injury group increased (P <0. 01) and the content of oxidized protein decreased (P < 0. 01). After genipin was administered, the expression of UCP2 decreased (P < 0. 05), and the expression of antioxidative protein increased (P < 0. 05). Experiments suggest that genipin has anantioxidant protective effect on MIN6 cells damaged by high glucose and maintains the function of MIN6cells to promote insulin secretion. This experiment provides experimental data for the antioxidation of genipin on MIN6 cells injured by high glucose, and also provides new ideas for the follow-up study of genipin in the treatment and prevention of diabetes.

Quantitative proteomics revealed extensive microenvironmental changes after stem cell transplantation in ischemic stroke / 医学前沿

The local microenvironment is essential to stem cell-based therapy for ischemic stroke, and spatiotemporal changes of the microenvironment in the pathological process provide vital clues for understanding the therapeutic mechanisms. However, relevant studies on microenvironmental changes were mainly confined in the acute phase of stroke, and long-term changes remain unclear. This study aimed to investigate the microenvironmental changes in the subacute and chronic phases of ischemic stroke after stem cell transplantation. Herein, induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) were transplanted into the ischemic brain established by middle cerebral artery occlusion surgery. Positron emission tomography imaging and neurological tests were applied to evaluate the metabolic and neurofunctional alterations of rats transplanted with stem cells. Quantitative proteomics was employed to investigate the protein expression profiles in iPSCs-transplanted brain in the subacute and chronic phases of stroke. Compared with NSCs-transplanted rats, significantly increased glucose metabolism and neurofunctional scores were observed in iPSCs-transplanted rats. Subsequent proteomic data of iPSCs-transplanted rats identified a total of 39 differentially expressed proteins in the subacute and chronic phases, which are involved in various ischemic stroke-related biological processes, including neuronal survival, axonal remodeling, antioxidative stress, and mitochondrial function restoration. Taken together, our study indicated that iPSCs have a positive therapeutic effect in ischemic stroke and emphasized the wide-ranging microenvironmental changes in the subacute and chronic phases.

Repair of tongue defect with submental artery island flap and free anterolateral thigh flap after resection of tongue cancer: A comparative analysis / 中华显微外科杂志

Objective:To compare and analyse the clinical outcome, advantages and disadvantages of submental artery island flap (SAIF) and free anterolateral thigh flap (ALTF) in the repair and reconstruction of tongue after radical surgery of tongue cancer.Methods:From January, 2016 to December, 2018, a total of 40 patients received tongue repair and reconstruction with either SAIF or ALTF after radical resection of tongue cancer. There were 28 males and 12 females, with an average age of 51 years old. Eighteen patients received tongue repair and reconstruction with SAIF and 22 with ALTF. Postoperative follow-up were carried out and the clinical data were collected. Swallowing, speech and softness of the tongue between the 2 repair methods were compared and statistically analysed. P<0.05 indicated a significant statistical difference between 2 groups. Results:All flaps survived. One ALTF had a venous vascular crisis. The flap survived after the removal of thrombus at the anastomotic site. Functional recovery of tongue was analysed after the follow-up of 12-48 months. It was found that there was no significant difference in speech function between the 2 groups (SAIF vs ALTF: 13 vs 15, P=0.206). The swallowing dysfunction in SAIF group was significantly higher than that of the ALTF group (SAIF vs ALTF: 15 vs 7, P=0.014). Moreover, the average time of surgery in SAIF group (3.5 h) was significantly less than that of the ALTF group (6.8 h), which had statistically significance ( P<0.05). Conclusion:The SAIF and ALTF are ideal flaps for repairing the tongue defect caused by tongue cancer surgery. SAIF features a simple surgical procedure and a short time for flap taking. ALTF provides sufficient amount of tissue to cover the scars left by the surgery, reduce donor site complications, and benefit the recovery of swallowing and speech functions.

The relationship between knee muscle strength and walking ability after incomplete lumbar spinal cord injury / 中华物理医学与康复杂志

Objective:To explore any correlation between knee muscle strength and walking ability after an incomplete lumbar spinal cord injury and the factors influencing walking ability.Methods:Twenty-seven persons with an incomplete lumbar spinal cord injury were tested. Their bilateral quadriceps and hamstring muscle strength and peak torque during knee extension and flexion were assessed. They completed the 10m walking time test (10MWT) and each person′s WWISCI II spinal cord injury walking index was evaluated. Spearman correlations among the data were computed and stepwise regression was used to analyze the factors significantly influencing the 10MWT and WISCI II results.Results:The average hamstring strength was significantly negatively correlated with the 10MWT times and WISCI II ratings. Hamstring torque also was negatively correlated with the 10MWT times, but positively correlated with the WISCI II ratings. The 10MWT times and WISCI II ratings were significantly inter-correlated. Hamstring strength was the best predictor of 10MWT times (accounting for 63% of the variance) and WISCI II ratings (64%), but quadriceps strength was also a secondary predictor.Conclusions:Knee muscle strength is a useful predictor of 10MWT times and WISCI II ratings after incomplete lumbar spinal cord injury. It can predict early walking ability to some extent.