Synthesis and anti-radiation activity evaluation of substituted 2H-benzopyran-3-formylaniline compounds / 军事医学

Objective To discover new-structure active molecules in order to provide candidate compounds for anti-radiation drug research.Methods Conformational fixation and functional group conversion strategies were used to modify the structure of Ex-RAD before substituted 2H-benzopyran-3-formylaniline compounds were designed and synthesized.The anti-radiation activities of the synthesized compounds were screened via irradiated cell survival models and the cytotoxicity of the active compounds was examined.Western blotting assay was used to investigate the effects of the optimal compound on the expressions of apoptosis related proteins in irradiated cells.The anti-radiation activity of the optimal compound was evaluated through irradiated mice models.Results Twenty-one target compounds were synthesized,eight of which were found to significantly improve the survival of irradiated cells.Four compounds were selected for re-screening and cytotoxicity evaluation.Compound D19 was determined as the optimal compound that could affect the expressions of apoptosis related proteins in irradiated AHH-1 cells by Western blotting assay.Compared with the radiation group,the 30-day survival rate of D19 treated mice irradiated with 8.6 Gy of whole-body radiation increased by 70%.D19 showed protective effect on the blood system of non-lethal dose irradiated mice.Conclusion The novel compound D19 has shown strong anti-radiation activity and deserves more research.

Construction and characterization of a mouse model of pneumonia caused by highly virulent and multi-drug resistant Pseudomonas aeruginosa / 军事医学

Objective To establish an inhalation infection pneumonia model of C57BL/6J mice with highly virulent and multi-drug resistant Pseudomonas aeruginosa(PA)strain F291007,and to study the microbiological,pathological and immunological characteristics of this model.Methods The strain F291007 was isolated and identified before the bacterial suspension was administered to the mice via aerosolized intratracheal inoculation to establish the pneumonia infection model.In the course of infection,the conditions and survival of the mice were observed,and the bacterial loads,the histopathological states and the cytokine expression levels in the major organs were detected.Finally,three key cytokines were blocked to observe the survival of mice.Results The strain F291007 was isolated and identified.After lethal dose infection,all the mice died within 24 h.After sub-lethal dose infection,a large number of immune cells in the body were capable of phagocytosis and killing of invading pathogens,which was manifested as rapid clearance of bacteria in lungs and the exponential decrease of bacterial load with the passage of time.The pathological changes in lungs were most severe at 1 to 3 days but gradually recovered.After infection,interleukin-6(IL-6),IL-17A and tumor necrosis factor-α(TNF-α)in alveolar lavage fluid and serum were significantly increased at 1 to 3 days.After blocking of these three cytokines with specific antibodies,the survival rates of infected mice decreased significantly.Conclusion A mouse model of gradually-recovered pneumonia infection caused by PA inhalation has been established,suggesting that the first one to three days are critical to immune response after infection through multiple indicators.This mouse model can be used for research on the pathogenesis,immunoregulation and treatment evaluation of highly virulent and multi-drug resistant PA inhalation pneumonia infection.

Expression of bone morphogenetic protein 9 in patients with sepsis-associated acute respiratory distress syndrome and its role in early recognition and prognosis prediction of disease / 中华急诊医学杂志

Objective:To observe the expression level of bone morphogenetic protein 9 (bone morphogenetic protein 9,BMP9) in patients with sepsis-associated acute respiratory distress syndrome (acute respiratory distress syndrome,ARDS), and to explore the role of BMP9 in early recognition and prognosis prediction of sepsis-associated ARDS.Methods:From May 2022 to May 2023, total of 56 patients with sepsis-associated ARDS in Shanxi Bethune Hospital were selected as the ARDS group, 49 patients with cardiogenic pulmonary edema as the case control group, and 46 adults who underwent physical examination in the physical examination center of our hospital as the healthy control group.The patients in the ARDS group were followed up for 28 days and divided into survival group ( n = 26) and death group ( n = 30). The expression level of serum BMP9 and its correlation with clinical indicators in each group were analyzed and compared. The risk factors of sepsis-associated ARDS were analyzed by Logistic regression, and the diagnostic efficacy and prognostic value of related indicators were analyzed. Results:The serum level of BMP9 in sepsis-associated ARDS group [1401.14 (856.59,1982.86) ]pg/mL was significantly higher than that in case control group (438.26±128.52) pg/mL and healthy control group (398.96±96.55)pg/mL, the differences were statistically significant ( P<0.01). In addition, BMP9 expression significantly correlated with procalcitonin, lymphocyte count and SOFA score ( P < 0.05, P < 0.01, respectively). Multivariate Logistic regression analysis showed that BMP9 was a high risk factor for the development of sepsis-associated ARDS ( P<0.01). The area under the ROC curve (area under the ROC curve,AUC) of BMP9 to predict the occurrence of sepsis-associated ARDS was 0.930. The specificity was 100.0% and the sensitivity was 80.4%, which was significantly higher than the specificity (89.8%) and sensitivity (67.9%) of the oxygenation index. Follow-up and comparison of BMP9 levels in patients with different prognosis of sepsis-associated ARDS showed that the expression level of BMP9 in the death group was higher than that in the survival group, and the difference was statistically significant ( P < 0.05). The ROC curve of BMP9 in predicting the prognosis of patients with sepsis-associated ARDS. The area under the ROC curve was 0.699, the sensitivity was 43.3%, and the specificity was 100.0%. Conclusions:The expression of BMP9 in sepsis-associated ARDS patients significantly increased, and its high expression was significantly correlated with inflammatory markers such as procalcitonin, lymphocyte count and SOFA score. BMP9 is an independent risk factor in patients with sepsis-associated ARDS, and it is promising as a new biomarker for early identification of sepsis-associated ARDS. However, it do not show a good predictive effect on the prognosis of the disease.

Phenotypic evaluation of Ttc37 knockout mouse as type Ⅰ tricho-hepato-enteric syndrome model / 复旦学报（医学版）

Objective To establish a mouse model of type Ⅰ tricho-hepato-enteric syndrome(THES)induced by Ttc37 deficiency.Methods Ttc37 flox strain was established by site-specifically inserted loxP sites into Ttc37 gene via CRISPR/CAS9 technology.Ubiquitously expressed CAG-Cre was introduced for all-tissue removal of Ttc37 in Ttc37flox/flox;CAG-Cre mice.The knock-out effect was confirmed by fluorescence quantitative PCR and Western blot.Phenotypic evaluations were conducted in 8-week-old mice including hematoxylin-eosin staining of skin,spleen,liver,bladder,and gastrointestinal tract(GI),serum enzyme activity assay of aspartate aminotransferase(AST)and alanine aminotransferase(ALT),measurement of serum hemoglobin level,and ELISA for IgG and IgM level upon antigen immunization.Results Similar to type Ⅰ THES patients,Ttc37flox/flox;CAG-Cre mice exhibited impaired development of hair shaft,epidermis,B cell and eyes,while liver,GI,bladder and serum hemoglobin level seemed normal under unstressed condition.Conclusion A novel mouse model of typeⅠ THES was constructed successfully,which was applicable for pathological study.

Superior vena cava syndrome and pulmonary artery stenosis in a patient with lung metastases of bladder cancer / 复旦学报（医学版）

Superior vena cava syndrome(SVCS)is a group of clinical syndromes caused by obstruction of the superior vena cava and its major branches from various causes.Pulmonary artery stenosis(PS)is a complication of lung cancer or mediastinal tumours.SVCS combined with PS due to pulmonary metastases from bladder cancer is extremely rare and has not been reported in the literature.Here we reported an old male patient with pulmonary metastases from bladder cancer presenting with swelling of the head,neck and both upper limbs.SVCS combined with PS was clarified by pulmonary artery computed tomography angiography(CTA)and digital subtraction angiography(DSA).Endovascular stenting was used to treat SVCS.Angiography also showed that PS had not caused pulmonary hypertension and did not need to be treated.The swelling of the patient's head,neck and upper limbs was gradually reduced after the procedure.

Correlation between the Expression of AHA1 mRNA and LOXL2 mRNA in Osteosarcoma Patients Tissues with mRNA Expression of Invasion and Metastasis Genes and Their Clinical Significance / 现代检验医学杂志

Objective To investigate the correlation between the expression of the activator of HSP90 ATPase-1(AHA1),lysyl oxidase like-2 protein(LOXL2)in osteosarcoma tissues with mRNA expression of invasion and metastasis genes and their clinical significance.Methods A total of 90 osteosarcoma patients diagnosed and treated in North China Medical and Health Group Fengfeng General Hospital from February 2016 to March 2017 were selected as the research object.The expression of AHA1 mRNA,LOXL2 mRNA and invasion and metastasis genes Wnt family member 9A(Wnt9a)mRNA,zinc finger E-box binding homologous box 1(ZEB1)mRNA,zinc finger E-box binding homologous box 1(ZEB2)mRNA,N-cadherin(N-cad)mRNA,and vimentin(Vim)mRNA in tissues were detected by real-time fluorescence quantitative PCR.Pearson correlation analysis was used for correlation analysis.The differences in expression of AHA1 mRNA and LOXL2 mRNA in osteosarcoma patients among different clinical characteristics were compared.Kaplan-Meier survival analysis was used to analyze the effect of AHA1 mRNA and LOXL2 mRNA on the prognosis of osteosarcoma patients.The prognostic factors of osteosarcoma patients were analyzed by univariate and multivariate COX regression.Results The expressions of AHA1 mRNA(3.16±0.59),LOXL2 mRNA(2.84±0.44)and invasion and metastasis genes[Wnt9a mRNA(3.23±0.42),ZEB1 mRNA(2.73±0.39),ZEB2 mRNA(2.52±0.56),N-cad mRNA(2.71±0.65)and Vim mRNA(2.81±0.73)]in osteosarcoma tissues were higher than those in paracancerous tissues(1.10±0.21,0.95±0.18,0.79±0.15,0.64±0.11,0.98±0.19,0.68±0.14,0.72±0.15),and the differences were statissically significant(t=31.206,37.716,51.903,48.931,24.706,28.964,26.605,all P<0.05).There was a significant positive correlation between AHA1 mRNA and LOXL2 mRNA expression in osteosarcoma(r=0.712,P<0.05).The expressions of AHA1 mRNA and LOXL2 mRNA were significantly positively correlated with the expressions of invasion and metastasis genes(Wnt9a,ZEB1,ZEB2,N-cad,and Vim mRNA)in tumor tissue of osteosarcoma group(r=0.504～0.720,all P<0.05).The expressions of AHA1 mRNA and LOXL2 mRNA in osteosarcoma tissues with Eneeking stage Ⅲ,soft tissue infiltration,and lung metastasis were higher than those in patients with Eneeking stage Ⅰ～Ⅱ,no soft tissue infiltration,and no lung metastasis,with significant differences(t=14.122～171.054,all P<0.05).The 5-year survival rates of patients in the AHA1 mRNA high expression group and low expression group were 36.36%(16/44)and 78.26%(36/46),respectively.The 5-year cumulative survival rate of patients in the AHA1 mRNA high expression group was significantly lower than that in the low expression group(Log-rank χ2=16.081,P<0.05).The 5-year survival rates of patients with high and low expression of LOXL2 mRNA were 34.88%(15/43)and 78.72%(37/47),respectively.The 5-year cumulative survival rate of patients in the LOXL2 mRNA high expression group was significantly lower than that in the low expression group(Log-rank χ2=15.880,P<0.05).Lung metastasis(OR=1.921,P<0.05),Eneeking stage Ⅲ(OR=1.906,P<0.05),AHA1 mRNA high expression(OR=1.405,P<0.05),and LOXL2 mRNA high expression(OR=1.733,P<0.05)were independent risk factors affecting the poor survival prognosis of osteosarcoma patients.Conclusion The expressions of AHA1 mRNA and LOXL2 mRNA in osteosarcoma were increased,and they were correlated with the expression of invasion and metastasis genes,indicating they may be independent risk factors affecting the poor survival and prognosis of osteosarcoma patients.

Effectiveness research of opportunistic screening for osteoporosis based on chest CT and deep convolutional neural network / 实用放射学杂志

Objective To analyze the feasibility and efficacy of a deep convolutional neural network(DCNN)model based on chest CT images to evaluate bone mineral density(BMD).Methods A total of 1 048 health check subjects'2 096 central level images of lumbar 1 and 2 vertebral bodies were used for experiments and analysis in this retrospective study.According to the results of quanti-tative computed tomography(QCT)BMD measurement,the subjects were divided into three categories:normal,osteopenia,osteopo-rosis(OP).Herein,a DCNN segmentation model was constructed based on chest CT images[training set(n=1 096),tuning set(n=200),and test set(n=800)],the segmentation performance was evaluated using the Dice similarity coefficient(DSC)to com-pare the consistency with the manually sketched region of vertebral body.Then,the DCNN classification models 1(fusion feature construction of lumbar 1 and 2 vertebral bodies)and model 2(image feature construction of lumbar 1 alone)was developed based on the training set(n=530).Model performance was compared in a test set(n=418)by the receiver operating characteristic(ROC)curve analysis.Results When the number of images in the training set(n=300)was adopted,the DSC value was 0.950 in the test set.The results showed that the sensitivity,specificity and area under the curve(AUC)of model 1 and model 2 in diagno-sing osteopenia and OP were 0.716,0.960,0.952;0.941,0.948,0.980;0.638,0.954,0.940;0.843,0.959,0.978,respectively.The AUC value of normal model 1 was higher than that of model 2(0.990 vs 0.983,P=0.033),while there was no significant difference in AUC values between osteopenia and OP(P=0.210,0.546).Conclusion A DCNN may have the potential to evaluate bone mass based on chest CT images,which is expected to become an effective tool for OP screening.

Best evidence summary of nutrition management in patients of acoustic neuroma during the perioperative period / 中国实用护理杂志

Objective:To summarize and evaluate the best evidence of perioperative nutrition management for patients with acoustic neuroma, and to provide evidence-based basis for clinical nurses.Methods:BMJ best clinical practice, UpToDate, Cochrane Library, Guidelines International Network, Scottish Intercollegiate Guidelines Network, the official website of Ontario Registered Nurses Association, JBI Australian evidence-based health care center, PubMed, Embase, CINAHL, Yimaitong, Chinese biomedical literature database, CNKI, Wanfang database and other domestic and foreign databases related to clinical practice guidelines, expert consensus, evidence summary, systematic evaluation, sysmtem analysis, clinical randomized scientific control were seached. The retrieval time was limited from June 1st, 2013 to June 1st, 2023. Evaluated the quality of the included literatures, and conduct evidence extraction, grade evaluation and summary analysis.Results:A total of 17 literatures were included, including 5 guidelines, 6 expert consensus, 2 best practices and evidence summary, 2 system evaluation and 2 randomized scientific control. A total 27 of best evidence was formed, covering five aspects: nutrition management team construction, screening and evaluation of nutrition and dysphagia, timing and implementation of nutrition support, specific measures of nutrition management, continuous nutrition management after discharge.Conclusions:This study summarized the best evidence of perioperative nutritional management of acoustic neuroma, and provides evidence-based basis for clinical nurses. However, its recommendations are not specialized, some of them are controversial, and come from many countries. In clinical practice, we should make a comprehensive analysis in combination with the actual clinical situation and other relevant factors, and make some choices, so as to promote the improvement of clinical nursing quality.

Advances in MRI studies of brain structure and cerebral blood perfusion in patients with bipolar disorder / 实用医学杂志

Bipolar disorder(BD)is a class of common psychiatric disorders,and its high morbidity,disability,and mortality have attracted widespread attention.However,in clinical practice,the initial accurate diagnosis rate of BD is low and easily misdiagnosed as monophasic depression.Many neuroimaging studies have shown that cortical thickness,gray matter,white matter,and functional activities are altered in some brain regions of BD patients.However,their specific neuroimaging indexes have not been clarified,and the specific pathophysi-ological mechanisms for the onset of BD have not been fully elucidated.Therefore,in this paper,we combed through the recent years of BD patients to study the cortical structure and perfusion of the brain to review the methods in anticipation of more in-depth research at a later stage.

Characteristics of hydrogel microspheres in bone tissue engineering / 中国组织工程研究

BACKGROUND:Hydrogel microparticles,due to their porous and injectable properties,have demonstrated unique advantages in biomedical fields,such as the delivery of cells and bioactive factors/drugs,the construction of tissue repair scaffolds.They have broad application prospects. OBJECTIVE:To review the latest research progress and discuss the key problems and challenges in the research of bone tissue engineering based on hydrogel microparticles. METHODS:The relevant articles in PubMed and CNKI were searched by computer.The English key words were"hydrogels,microparticles,microspheres,microcarriers,bone,bone defect,bone repair,bone healing,bone tissue engineering"while the Chinese key words were"hydrogels,microparticles,microspheres,bone tissue engineering,bone defect,bone repair,bone regeneration".The retrieval period was from 2002 to 2022,and 127 articles were finally included for review. RESULTS AND CONCLUSION:(1)At present,various hydrogel microparticles have been developed for use in bone tissue engineering strategies,for example,hydrogel microparticles carrying cells or bioactive factors/drugs,hydrogel microparticles as biological scaffolds,stimulus-responsive hydrogel microparticles,biomineralized hydrogel microparticles,hydrogel microparticles combined with other biological materials.(2)Bone tissue engineering repair strategies based on hydrogel microparticles mainly regulate bone repair by promoting stem cell recruitment and osteogenic differentiation,regulating the local inflammatory microenvironment and promoting angiogenesis at the site of injury.However,the present studies did not deeply explore the effect of bone tissue engineering based on hydrogel microparticles on the recruitment and differentiation of endogenous stem cells and the regulation of the inflammatory microenvironment by the physical and chemical properties of hydrogel microparticles.The long-term in vivo adverse reactions of hydrogel microparticles have not been explored yet,and it is difficult to mass-produce them,thus future research needs to strengthen the mechanism exploration and technical route,so as to provide a reasonable reference for the development of hydrogel microparticles that can be used for clinical transformation.

Ischemia-reperfusion injury in total knee arthroplasty / 中国组织工程研究

BACKGROUND:The mechanism,manifestation,prevention and treatment of ischemia-reperfusion injury have been reported in the past.However,there are few studies on the ischemia-reperfusion injury of lower limb skeletal muscle caused by total knee arthroplasty.This article focuses on the pathogenesis,clinical impact,prevention and treatment of the ischemia-reperfusion injury of lower limb caused by total knee arthroplasty. OBJECTIVE:To summarize the related literature of lower limb ischemia-reperfusion injury caused by total knee arthroplasty,analyze the mechanism and significance,and give hints for further research on skeletal muscle ischemia-reperfusion injury. METHODS:The relevant articles on PubMed,CNKI,WanFang and VIP databases published from January 1,2000 to April 30,2022 were searched by computer with the Chinese and English search terms of"ischemia-reperfusion injury,total knee arthroplasty,tourniquet,mechanism,pathophysiology,skeletal muscle,treatment".After excluding repetitive research and some basic articles with low correlation,68 articles were finally selected for review. RESULTS AND CONCLUSION:(1)The pathogenesis of ischemia-reperfusion injury is related to oxygen free radicals,intracellular calcium overload,neutrophil activation,as well as high concentration of nitric oxide,no reflow phenomenon,apoptosis and other mechanisms.More detailed mechanism research can provide basis for future prevention and treatment.(2)Ischemia-reperfusion injury of lower limbs will cause local skeletal muscle injury,which may be caused by the trauma of the operation itself or the role of ischemia-reperfusion injury.More targeted research is needed to distinguish the relationship between the two.(3)Ischemia-reperfusion injury of lower limbs may even affect the distal organs,causing kidney and lung damage.It also affects local and systemic circulation.(4)To clarify the effect of ischemia-reperfusion injury can point out the direction for future prevention and treatment.The current prevention and treatment measures mainly include ischemic preconditioning,anesthetic,antioxidant and other drug prevention.(5)The detailed review of ischemia-reperfusion injury of lower limb skeletal muscle caused by total knee arthroplasty can provide basis for future diagnosis and treatment decisions.

Signaling pathway of dexmedetomidine against ischemia-reperfusion injury / 中国组织工程研究

BACKGROUND:Dexmedetomidine has the effect of anti-ischemia-reperfusion injury,but the comprehensive and systematic review of its signaling pathway is less. OBJECTIVE:To focus on the review of dexmedetomidine's signaling pathway in the mechanisms of antioxidant stress,inhibition of inflammation,anti-apoptosis,autophagy,and so on. METHODS:The relevant articles on PubMed,CNKI,WanFang,and VIP databases were searched by computer with the key words"ischemia-reperfusion inquiry;dexmedetomidine;signal path;oxidative stress;inflammation;apoptosis"in Chinese and English.After excluding repetitive research and some basic articles with low correlation,57 articles were finally included for review. RESULTS AND CONCLUSION:(1)Dexmedetomidine plays an important role in organ protection through many mechanisms,such as anti-oxidative stress injury,anti-inflammation,anti-apoptosis and autophagy.This involves many pathways,including Nrf2 and its downstream protein antioxidant stress pathway,Toll-like receptor 4 family and nuclear factor-κB-related anti-inflammatory pathway,JAK2/STAT3-related anti-inflammatory pathway,and cholinergic anti-inflammatory pathway,and the cholinergic pathway is the upstream mechanism of many nuclear factor-κB signaling pathways.(2)PI3K/Akt pathway plays different roles according to its activated downstream signals,inhibiting the activation of NLRP3 inflammatory body,activating signal molecules endothelial nitric oxide synthase,mammalian target of rapamycin,and hypoxia-inducible factor 1α to play an anti-inflammatory role,and activate Bad or Bax residues to play an anti-apoptotic role,and PI3K/Akt activates glycogen synthetase kinase-3β.It can also play an anti-inflammatory and anti-apoptotic role.(3)Dexmedetomidine activates SIRT3 to mediate anti-apoptosis and inhibit endoplasmic reticulum stress to produce anti-apoptosis.(4)The detailed review of the anti-ischemia-reperfusion injury signaling pathway of dexmedetomidine can provide a basis for future mechanism research and diagnosis and treatment decisions.

Effects of silver needle-thermal conduction therapy on skeletal muscle mitochondria and silent information regulator homolog 3 expression in a rat model of myofascial pain syndrome / 中国组织工程研究

BACKGROUND:Clinical studies have found good analgesic effects of silver needle-thermal conduction therapy in patients with myofascial pain syndrome,but the exact mechanism remains unclear. OBJECTIVE:To observe the effect of silver needle-thermal conduction therapy on silent information regulator homolog 3(SIRT3)changes and mitochondrial ultrastructure in a rat model of myofascial pain syndrome. METHODS:Twenty rats were randomly selected from 26 Sprague-Dawley rats and were subjected to percussion combined with motor fatigue for replicating the rat model of myofascial pain syndrome.Sixteen rats that were successfully modeled were randomly divided into model group and silver needle-thermal conduction therapy group(treatment group),with eight rats in each group.The remaining rats were used as controls(normal group).The treatment group was treated with silver needle-thermal conduction therapy.Mechanical withdrawal threshold and thermal withdrawal latency of rats were measured at 1 day before modeling,1 day after modeling and 14 days after treatment.Electromyographic activities of the right medial femoral muscle were measured at 14 days after treatment.The right medial femoral muscle tissue was taken for hematoxylin-eosin staining to observe the local morphology and for transmission electron microscopy to observe the mitochondrial ultrastructure.Western blot assay was performed to detect SIRT3 expression. RESULTS AND CONCLUSION:Pain threshold:The mechanical withdrawal threshold and thermal withdrawal latency of the model and treatment groups were significantly decreased compared with those in the normal group and before modeling(P＜0.01).After treatment,the mechanical withdrawal threshold and thermal withdrawal latency of rats were significantly higher in the treatment group compared with the model group(P＜0.01).Electromyography:The rats in the model group showed spontaneous electrical activity in the right medial femur,while the rats in the treatment group showed reduced spontaneous electrical activity,longer time frame(P＜0.01)and lower wave amplitude(P＜0.05)compared with the model group.Hematoxylin-eosin staining:In the normal group,rat muscle fibers arranged closely and regularly.In the model group,the muscle fibers of rats were atrophied,degenerated,and disordered in arrangement.In the treatment group,rat muscle structure disorder improved.Mitochondrial microstructure:Under the transmission electron microscope,mitochondrial structure in the normal group was normal;mitochondrial swelling with broken or disappeared cristae appeared in the model group;mitochondrial swelling in the treatment group was obviously relieved or tended to be normal.SIRT3 expression:SIRT3 expression was significantly downregulated in the model group compared with the normal group,but was significantly upregulated in the treatment group compared with the model group(P＜0.05).To conclude,abnormalities in local muscle mitochondria and downregulation of SIRT3 expression suggest the presence of impaired energy metabolism in the rat model of myofascial pain syndrome.Mitochondrial changes recover and are close to normal after the silver needle-thermal conduction therapy,and the expression of SIRT3 is also upregulated close to the normal group,indicating the silver needle-thermal conduction therapy may play a therapeutic role by promoting mitochondrial repair and improving energy metabolism disorder.

Protective effects of Ginkgo biloba extract on presbycusis in the rat model via autophagy pathway / 中成药

AIM To investigate the effects of Ginkgo biloba extract on hearing function,cochlear morphology and autophagy-related protein expression in a rat model of presbycusis.METHODS Forty-five rats were randomly divided into the control group,the model group and the low,medium and high dose G.biloba extract groups(10,20 and 30 mg/kg),with 9 rats in each group.The rat model of presbycusis was established by intraperitoneal injection of 500 mg/kg D-galactose(D-gal).Eight weeks after the corresponding administration,the rats had their changes of hearing threshold detected by the auditory brainstem evoked potential(ABR);their morphological changes of cochlear hair cells,stria vascularis(SV)and spiral ganglion cells observed by HE staining;their number of hair cells inside and outside the cochlea detected by immunofluorescence staining;their ultrastructure changes of cochlear hair cells observed by transmission electron microscopy;and their expression of autophagy-related proteins in cochlea tissue detected by Western blot.RESULTS Compared with the control group,the model group displayed increased ABR threshold(P<0.01);more severely damaged inner and outer hair cells,spiral ganglion cells and SV,decreased SV thickness and numbers of spiral ganglion cells,inner and outer hair cells and autophagosomes(P<0.01);decreased protein expressions of Beclin1 and LC3 Ⅱ and ratio of LC3 Ⅱ/LC3 Ⅰ in cochlear tissue(P<0.01),and higher P62 protein expression(P<0.01).Compared with the model group,the medium and high dose G.biloba extract groups shared decreased ABR thresholds(P<0.01);improved morphology of inner and outer hair cells and SV in the cochlea,normalized,morphology of spiral ganglion cells,and increased SV thickness and the numbers of spiral ganglion cells,inner and outer hair cells and autophagosomes(P<0.05,P<0.01);increased protein expressions of Beclin1 and LC3 Ⅱ and the ratio of LC3 Ⅱ/LC3 Ⅰ in the cochlea(P<0.01),and decreased P62 protein expression(P<0.01).CONCLUSION The protective effects G.biloba extract on hearing function and cochlear cells in the rat model of presbycusis may be associated with the up-regulated expression of Beclin1 and LC3 Ⅱ proteins and down-regulated P62 protein expression in cochlear tissues.

Comparison of the short-term outcomes in very/extremely low birth weight infants supplemented with fortified donor human milk or preterm formula / 中华围产医学杂志

Objective:To compare the short-term outcomes of very low birth weight (VLBW) and extremely low birth weight (ELBW) infants supplementarily fed with fortified donor human milk (DHM) or preterm formula (PF) when the mother's own milk (MOM) is insufficient.Methods:This retrospective cohort study included 91 VLBW or ELBW preterm infants with birth weight<1 500 g who were hospitalized in Peking Union Medical College Hospital from October 1, 2017, to September 30, 2020. Based on the supplemental feeding method when MOM was insufficient, these infants were divided into the DHM group ( n=51) and PF group ( n=40). Mann-Whitney U, t-test, Chi-square test, or Fisher's exact test were used to compare the short-term clinical outcomes during hospitalization between the two groups. Results:(1) There were no statistically significant differences between the 91 preterm infants in the DHM group and PF group in their gestational age, birth weight, sex ratio, birth mode, mothers' age at delivery, or the proportion of infants of small gestational age (all P>0.05). (2) The feeding volume in the DHM group was significantly greater than that in the PF group on the 14th day after birth [(108.2±53.1) vs. (81.0±47.8) ml/(kg·d), t=0.78, P=0.020]. Moreover, the time to achieve the feeding amounts up to 120 ml/(kg·d) and 150 ml/(kg·d) for infants in the DHM group were significantly shorter than those in the PF group [(17.5±10.2) vs. (30.0±12.0) d, t=4.38; (22.1±13.3) vs. (32.3±11.9) d, t=0.02; both P<0.05]; (3) Lower proportion of peripherally inserted central catheter (PICC) [58.8% (30/51) vs. 100% (40/40), χ 2=21.88, P<0.001] and shorter PICC duration were observed in the DHM group [10.0 (0.0-19.0) vs. 29.0 (17.0-40.5) d, Z=5.56, P<0.001] compared to the PF group. The times of red blood cell transfusions and the incidence of late sepsis in the DHM group were less than those in the PF group [0.0 (0.0-2.0) vs. 2.0 (1.0-3.0) times, Z=4.44, P<0.001; 23.5% (12/51) vs. 50.0% (20/40), χ 2=6.39, P=0.011]. There were no statistically significant differences observed in the incidence of bronchopulmonary dysplasia, neonatal necrotizing enterocolitis, retinopathy of prematurity, and the length of hospitalization (all P>0.05). Conclusion:When MOM is insufficient, supplementing VLBW and ELBW infants with fortified donor human milk can shorten the time to achieve enteral nutrition and reduce the use rate and time of PICC, the incidence of late-onset sepsis, and the times of red blood cell transfusion.

Serum vitamin D level of children aged 0 to 3 years and its correlation with nutritional knowledge, attitude and behavior of caregivers in Yibin / 中国儿童保健杂志

【Objective】 To explore the correlation of serum vitamin D level of children aged 0 to 3 years with their caregivers′ nutritional knowledge, attitude and practice (KAP) in Yibin, in order to provide reference for the prevention of vitamin D deficiency in children. 【Methods】 A total of 783 children aged 0 to 3 years who underwent child health care at the First People′s Hospital of Yibin from January to December 2020 were selected into this study. Children′s general conditions (feeding, growth and development, lifestyle, etc.) were collected, and venous blood samples were taken to detect serum 25-(OH)D concentration using the chemiluminescence method. The caregivers′ nutritional KAP was investigated using a self-designed knowledge-attitude-practice questionnaire. The relationship between the children′s vitamin D nutritional status and their caregivers′ nutritional KAP was analyzed using pearson correlation analysis. 【Results】 1) The exclusive breastfeeding rate of children aged 0 to 3 years was about 62.2%. Significant differences were found in outdoor activity time and average vitamin D supplementation among different age groups (t=9.030, 10.260, P<0.05). 2) The average concentration of serum 25-(OH)D was (36.8±8.7)ng/mL, and the incidence of vitamin D deficiency was 21.84%. Significant differences were found in serum 25-(OH)D level and the incidence of vitamin D deficiency among children of different ages, body shapes, outdoor activities, and vitamin D supplementation (t/F: 2.220 - 6.302, χ2: 5.346 - 33.134, P<0.05). 3) The caregivers′ nutritional KAP scores were 78.9±9.9, 88.1±8.3, and 78.3±11.8, respectively, with parents scoring higher than other caregivers (P<0.05). 4) Serum 25-(OH)D level was positively correlated with the nutritional knowledge, attitude, and behavior scores of caregivers (r=0.805, 0.650, 0.831, P<0.05). The caregivers′ nutritional KAP grade was correlated with vitamin D deficiency (P<0.05). 5) Overweight/obesity was a possible risk factor for vitamin D deficiency in children (OR=2.126, 95%CI: 1.162 - 3.887). Outdoor activity duration ≥2h/d (OR=0.592, 95%CI: 0.392 - 0.895), regular vitamin D supplementation (OR=0.618, 95%CI: 0.456 - 0.838), and good nutritional behavior of caregivers(OR=0.725, 95%CI: 0.563 - 0.933) were protective factors for vitamin D deficiency in children (P<0.05). 【Conclusions】 The prevalence of vitamin D deficiency is high among children aged 0 to 3 years in Yibin, and it is related to the nutritional KAP of their caregivers. Improving the nutritional KAP of caregivers can help prevent and manage vitamin D deficiency in children.

The Effect of Yangyin Xifeng Tongluo Formula （养阴熄风通络方） and Its Core Herb-Pairs on Prevention of Aconitine-Induced Ventricular Precontraction in Rats / 中医杂志

ObjectiveTo observe the effect of Yangyin Xifeng Tongluo Formula （养阴熄风通络方） and its core herbs combination on prevention of ventricular precontraction （PVC）. MethodsExperiment 1： Forty SD rats were randomly divided into model group， formula group， core herb-pairs medium-dose group and amiodarone group， with 10 rats in each group. Rats in the model group were given 10 ml/（kg·d） of pure water by gavage， rats in the formula group were given 1.125 g/（kg·d） of Yangyin Xifeng Tongluo Granules （养阴熄风通络方颗粒） by gavage， rats in the core herb-pairs medium-dose group were given 0.585 g/（kg·d） of granules of core herb-pairs by gavage， and rats in the amiodarone group were given 18 mg/（kg·d） of amiodarone hydrochloride tablets by gavage. The rats in each group were gavaged once a day for 14 consecutive days， and then a PVC model was established using rat tail vein injection of aconitine 25 μg/kg to compare the mortality and incidence of PVC， ventricular tachycardia （VT） and ventricular fibrillation （VF）， the time of the appearance of PVC， and the duration of PVC in the rats in each group. Experiment 2： Sixty SD rats were randomly divided into model group， the amiodarone group， and the core herb-pairs of low， medium and high dose groups， 12 rats in each group. Rats in the model group were gavaged with 10 ml/（kg·d） of purified water， rats in the low， medium， and high dose groups were gavaged with 0.2925， 0.585， and 1.17 g/（kg·d） of the core herb-pairs granules respectively， and rats in the amiodarone group were gavaged with 18 mg/（kg·d） of amiodarone hydrochloride tablets. All of them were gavaged once a day. After 14 days， rats in each group were injected intravenously into the tail vein with aconitine 25 μg/kg， and then the rats in each group were observed to show the mortality and incidence of PVC， VT and VF， and the time of appearance and duration of PVC. ResultsExperiment 1： Compared with the model group， The difference in the incidence of PVC in rats of all groups was not statistically signi-ficant （P＞0.05）， and the mortality and incidence of VT and VF in rats in the formula group， the core herb-pairs medium-dose group， and the amiodarone group significantly reduced， with delayed time of the occurrence of PVC and shorter duration of the PVC （P＜0.05 or P＜0.01） as compared with the model group， whereas the difference between each group with medication intervention was not statistically significant （P＞0.05）. Experiment 2： There was no statistically significant difference in the incidence of PVC in all groups （P＞0.05）， and the mortality and incidence of VT and VF reduced in the core herb-pairs of low-， medium-， and high-dose groups and in the amiodarone group， and the appearance of PVC delayed and its duration shortened （P＜0.05 or P＜0.01） as compared with the control group， whereas the differences were not statistically significant in the comparison among groups with medication （P＞0.05）. ConclusionBoth Yangyin Xifeng Tongluo Formula and its core herb-pairs could delay the time of occurrence and shorten the duration of PVC.

Correlation Analysis of Myelosuppression after Chemotherapy for Triple-Negative Breast Cancer and Its Prognosis / 中山大学学报(医学科学版)

ObjectiveTo investigate whether severe myelosuppression after chemotherapy is associated with prognosis in patients with breast cancer. MethodsTriple negative breast cancer （TNBC） patients who received chemotherapy at the Second Affiliated Hospital of Nanchang University from May 2， 2013 to May 2， 2018 were divided into a control group （no/mild myelosuppression） and a case group （severe myelosuppression）. In this study， 251 patients with TNBC met the inclusion and exclusion criteria， including 125 patients in the control group （20 patients with grade 0 myelosuppression， 43 patients with grade I myelosuppression， 62 patients with grade Ⅱ myelosuppression）， 126 patients in the case group （114 patients with grade Ⅲ myelosuppression， 12 patients with grade Ⅳ myelosuppression）. The general clinicopathological data of the patients in the two groups， including age， pathological type of tumor， tumor T stage， tumor N stage， tumor Nottingham grade， intravascular cancer thrombus， were analyzed using the χ2 test. The disease-free survival （DFS） and overall survival （OS） of the two groups were analyzed using the Kaplan-Meier method. A Cox proportional hazards regression model with multiple factors was used to analyze the impact of post-chemotherapy severe myelosuppression on disease-free survival （DFS） and overall survival （OS） in patients with TNBC. ResultsThe differences in general clinicopathologic data between the two groups of patients were not statistically significant （all P＞0.05）. The 5-year disease-free survival （DFS） rate was significantly lower in the control group compared with the case group （75.2% vs. 85.7%， P=0.027）. However， there was no statistically significant difference in the 5-year overall survival （OS） rate between the two groups （88.8% vs. 95.2%， P=0.057）. The analysis of the multifactorial Cox proportional hazards regression model revealed that post-chemotherapy severe myelosuppression was an independent protective factor for disease-free survival （DFS） （HR=0.332， 95% CI： 0.173-0.638， P=0.001） and overall survival （OS） （HR=0.193， 95% CI： 0.062-0.602， P=0.005） in TNBC patients. ConclusionOur results show that TNBC patients with severe myelosuppression after chemotherapy have longer disease-free survival （DFS） than those with no/mild myelosuppression， and overall survival （OS） also tend to be prolonged compared with those with no/mild myelosuppression， and severe myelosuppression after chemotherapy can be used as an independent predictor of a good prognosis in breast cancer.

Jiawei Wendantang Regulates NF-κB/NLRP3 Pathway to Reduce Inflammation in Rat Model of Diabetic Atherosclerosis / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Jiawei Wendantang in preventing and treating diabetic atherosclerosis by observing the effect of this prescription on the nuclear factor-κB / NOD-like receptor protein 3（NF-κB/NLRP3） pathway and related inflammatory cytokines in rat model of diabetic atherosclerosis. MethodFifty-four SPF-grade rats were randomized into blank， model， atorvastatin （0.9 mg·kg-1·d-1）， and high-， medium-， low-dose （18.2， 9.1， 4.55 g·kg-1·d-1， respectively） Jiawei Wendantang groups. The rats in other groups except the blank group were modeled for diabetic atherosclerosis by intraperitoneal injection of streptozotocin and feeding with a high-sugar high-fat diet， and those in the blank group were injected with an equal dose of citric acid buffer and fed with a regular diet. The drug administration lasted for 4 weeks， and the blood glucose level in the tail vein was measured every 6 days. After the last administration， the rats were anesthetized for sample collection. Enzyme-linked immunosorbent assay was employed to measure the serum levels of interleukin-18 （IL-18）， C-reactive protein （CRP）， tumor necrosis factor-α （TNF-α）， and intercellular adhesion molecule-1 （ICAM-1）. Western blot was employed to determine the relative protein levels of NF-κB p65， NLRP3， and ICAM-1 in the abdominal aorta. Real-time quantitative polymerase chain reaction was employed to determine the mRNA levels of NLRP3 and interleukin-1β （IL-1β） in the abdominal aorta. The pathological changes in the thoracic aorta were observed by hematoxylin-eosin staining. ResultCompared with the blank group， the model group showed elevated levels of IL-18， CRP， TNF-α， and ICAM-1 in the serum and blood glucose （P<0.05， P<0.01）， up-regulated protein levels of NF-κB p65， NLRP3， and ICAM-1 （P<0.01）， and up-regulated mRNA levels of NLRP3 and IL-1β （P<0.05）. Compared with model group， Jiawei Wendantang lowered the levels of IL-18， CRP， TNF-α， ICAM-1 and blood glucose （P<0.05， P<0.01）， down-regulated the protein levels of NF-κB p65， NLRP3， and ICAM-1 （P<0.01）， and down-regulated the mRNA levels of NLRP3 and IL-1β （P<0.05， P<0.01）. Moreover， Jiawei Wendantang alleviated the pathological injuries in the thoracic aorta. ConclusionJiawei Wendantang may modulate the NF-κB/NLRP3 signaling pathway to reduce the release and adhesion of inflammatory cytokines and regulate the blood glucose level to treat diabetic atherosclerosis.

The lncSIL molecule exerts a negative regulatory effect on the alveolar epithelial-mesenchymal transition induced by TGF-β1 through modulation of the EZH2/P21/CDK6 signaling pathway / 安徽医科大学学报

Objective @#To investigate the role of lncSIL in transforming growth factor-β1(TGF-β1)-induced alveo- lar epithelial interstitial transformation (EMT) and its related signaling pathways .@*Methods @#Western blot was used to detect the effect of lncSIL silencing on the expression of E-cadherin ( E-cad) , alpha-smooth muscle actin ( α- SMA) and Collagen I (Col I) in the process of EMT induced by TGF-β1 . LncSIL interacting proteins were ana- lyzed by RNA pulldown . Western blot was used to detect the effect of overexpression or silencing of lncSIL on the expression of its target gene enhancer of zeste homolog 2 (EZH2) and its downstream factors P21 and cyclin-de- pendent kinase 6 (CDK6) . Flow cytometry was used to analyze the effect of lncSIL on cell cycle progression .@*Results@#After lncSIL silencing , the expression of α-SMA and Col I increased , the expression of E-cad decreased . RNA pulldown assay showed that EZH2 was the target protein that interacted with lncSIL , and the expression of EZH2 increased after silencing lncSIL , the expression of EZH2 downstream gene P21 decreased , CDK6 increased . Flow cytometry showed that the number of cells in S phase significantly increased . When lncSIL was overexpressed , the expression of EZH2 and CDK6 was down-regulated , the expression of P21 was up-regulated , and the number of S phase cells significantly decreased .@*Conclusion @#LncSIL inhibits TGF-β1-induced alveolar epithelial cell mesen- chymal transition by negatively regulating EZH2/P21 /CDK6 signaling pathway to inhibit cell cycle progression .