Proteomic analysis and validation of DNA repair regulation in the process of hepatocellular carcinoma recurrence / 临床肝胆病杂志

ObjectiveTo investigate the role and mechanism of DNA repair regulation in the process of hepatocellular carcinoma （HCC） recurrence. MethodsHCC tissue samples were collected from the patients with recurrence within two years or the patients with a good prognosis after 5 years， and the Tandem Mass Tag-labeled quantification proteomic study was used to analyze the differentially expressed proteins enriched in the four pathways of DNA replication， mismatch repair， base excision repair， and nucleotide excision repair， and the regulatory pathways and targets that play a key role in the process of HCC recurrence were analyzed to predict the possible regulatory mechanisms. The independent samples t-test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsFor the eukaryotic replication complex pathway， there were significant reductions in the protein expression levels of MCM2 （P=0.018）， MCM3 （P=0.047）， MCM4 （P=0.014）， MCM5 （P=0.008）， MCM6 （P=0.006）， MCM7 （P=0.007）， PCNA （P=0.019）， RFC4 （P=0.002）， RFC5 （P<0.001）， and LIG1 （P=0.042）； for the nucleotide excision repair pathway， there were significant reductions in the protein expression levels of PCNA （P=0.019）， RFC4 （P=0.002）， RFC5 （P<0.001）， and LIG1 （P=0.042）； for the base excision repair pathway， there were significant reductions in the protein expression levels of PCNA （P=0.019） and LIG1 （P=0.042） in the HCC recurrence group； for the mismatch repair pathway， there were significant reductions in the protein expression levels of MSH2 （P=0.026）， MSH6 （P=0.006）， RFC4 （P=0.002）， RFC5 （P<0.001）， PCNA （P=0.019）， and LIG1 （P=0.042） in recurrent HCC tissue. The differentially expressed proteins were involved in the important components of MCM complex， DNA polymerase complex， ligase LIG1， long patch base shear repair complex （long patch BER）， and DNA mismatch repair protein complex. The clinical sample validation analysis of important differentially expressed proteins regulated by DNA repair showed that except for MCM6 with a trend of reduction， the recurrence group also had significant reductions in the relative protein expression levels of MCM5 （P=0.008）， MCM7 （P=0.007）， RCF4 （P=0.002）， RCF5 （P<0.001）， and MSH6 （P=0.006）. ConclusionThere are significant reductions or deletions of multiple complex protein components in the process of DNA repair during HCC recurrence.

Research status of correlation between myopia and accommodative function / 国际眼科杂志(Guoji Yanke Zazhi)

Ocular accommodation refers to the process by which the ciliary muscle creates a clear image of the object in the retina by changing the refractive power of the lens. When the accommodation ability of the eye is insufficient, the imaging focus falls on the region behind the retina and hyperopic defocus is easily formed, resulting in axial growth and leading to the development of myopia, and it is found that most myopic patients usually have some accommodation dysfunction. Myopia has become a public health problem in China, and the prevalence of adolescents has increased dramatically. How to prevent and stop the occurrence and development of myopia is a major challenge. Previous studies have found that ocular accommodation dysfunction is associated with the occurrence and development of myopia, and the measurement of parameters related to accommodation function has certain guiding significance for the prevention and control of myopia. The purpose of this paper is to review the correlation between myopia and ocular accommodation function, with a view to providing new ideas for the prevention, control and treatment of myopia.

Cloning and Expression Analysis of Squalene Epoxidase Gene in Poria cocos / 中国实验方剂学杂志

ObjectiveTo clone squalene epoxidase （SE）， a potential key rate-limiting enzyme involved in the synthesis pathway of Poria cocos triterpenes， from P. cocos and analyze for bioinformatics and expression. MethodThe total RNA was extracted by the kit and reverse-transcribed to cDNA. Specific primers were designed， and the cDNA was used as a template for cloning the SE gene， which was analyzed for bioinformatics. The expression of P. cocos qualene epoxidase（PcSE） was examined by Real-time polymerase chain reaction（Real-time PCR） in P. coco Shenzhou No. 10， Xiangjing 28， and 5.78 strains. ResultThe full length of PcSE is 1 571 bp， containing four exons and three introns. The obtained CDS sequence is 1 413 bp， encoding 470 amino acids. This protein is a hydrophobic protein with no signal peptide structure and has two transmembrane structural domains with a FAD/NAD （P） binding domain and SE structural domain localized to the mitochondrial membrane and the plasma membrane. The homologous sequence alignment with fungi of the Poriferae family is 80.92%， and the phylogenetic tree shows that PcSE protein is most closely related to P. cocos from the US. The results of Real-time PCR showed that the PcSE was expressed in all three strains， with the highest expression in 5.78 strain， and there was no significant difference in PcSE expression among the three strains. ConclusionFor the first time， the PcSE gene was cloned and analyzed from P. cocos， providing a basis for further research on the function of PcSE and the analysis of P. cocos triterpene biosynthesis pathway.

A Brief Discussion on the in Vitro Diagnostic Reagent Inspection Practice of Self-examination Management Regulations for Medical Device Registration / 中国医疗器械杂志

On October 21, 2021, the National Medical Products Administration issued and implemented the Self-examination Management Regulations for Medical Device Registration. The regulations clarify the specific requirements of the registration applicants in the process of self-examination, and put forward detailed requirements from the aspects of self-examination ability, self-examination report, declaration materials and responsibility requirements, so as to ensure the orderly development of the self-examination of medical device registration. Based on the actual verification work of in vitro diagnostic reagent, this study briefly discussed the understanding of the relevant contents of the regulations, aiming to provide some reference for enterprises and related supervision departments that have the requirement of registered self-examination.

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell Transplantation with Decitabine-containing Regimen in Myelodysplastic Syndromes and Myelodysplastic Syndromes Transformed Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with decitabine (Dec)-conditioning regimen in the treatment of myelodysplastic syndrome (MDS) and MDS transformed acute myeloid leukemia (MDS-AML).@*METHODS@#The characteristics and efficacy data of 93 patients with MDS and MDS-AML who received allo-HSCT in our center from April 2013 to November 2021 were retrospectively analyzed. All patients were administered by myeloablative conditioning regimen containing Dec (25 mg/m2 /d×3 d).@*RESULTS@#Among the 93 patients, 63 males and 30 females, were diagnosed as MDS（n ＝77）, MDS-AML（n ＝16）. The incidence of I/II grade regimen-related toxicity (RRT) was 39.8%, and III grade RRT was only found in 1 patient (1%). Neutrophil engraftment was successful in 91 (97.8%) patients after a median neutrophil engraftment time of 14 (9-27) days; Successful platelet engraftment was achieved in 87 (93.5%) patients, with a median engraftment time of 18 (9-290) days. The incidence of acute graft versus host disease（aGVHD） and grade III-IV aGVHD was 44.2% and 16.2%, respectively. The incidence of chronic graft versus host disease（cGVHD） and moderate-to-severe cGVHD was 59.5% and 37.1%, respectively. Of the 93 patients, 54 (58%) developed posttransplant infections, among which lung infection (32.3%) and bloodstream infection (12.9%) were the most common. The median follow-up after transplantation was 45 (0.1-108) months. The 5-year overall survival (OS) rate, disease-free survival (DFS) rate, treatment-related mortality, and cumulative incidence of relapse were 72.7%, 68.4%, 25.1%, and 6.5%, respectively. And the 1-year graft-versus-host disease/relapse-free survival rate was 49.3%. The patients in different group of relative high-risk prognostic scoring or low-risk prognostic scoring, with or without poor-risk mutation(s), with mutations number ≥3 or <3 had similar 5-year OS rate (more than 70%). Multivariate analysis showed that the incidence of grade III-IV aGVHD was the independent risk factor affecting OS（P =0.008）and DFS (P =0.019).@*CONCLUSION@#Allo-HSCT with Dec-conditioning regimen is feasible and effective in the treatment of patients with MDS and MDS-AML, especially those in high prognostic risk and with poor-risk mutations.

Research progress in role of autophagy in diabetic wound healing and traditional Chinese medicine intervention / 中国中药杂志

Diabetic ulcer(DU) is a chronic and refractory ulcer which often occurs in the foot or lower limbs. It is a diabetic complication with high morbidity and mortality. The pathogenesis of DU is complex, and the therapies(such as debridement, flap transplantation, and application of antibiotics) are also complex and have long cycles. DU patients suffer from great economic and psychological pressure while enduring pain. Therefore, it is particularly important to promote rapid wound healing, reduce disability and mortality, protect limb function, and improve the quality of life of DU patients. By reviewing the relevant literatures, we have found that autophagy can remove DU wound pathogens, reduce wound inflammation, and accelerate ulcer wound healing and tissue repair. The main autophagy-related factors microtubule-binding light chain protein 3(LC3), autophagy-specific gene Beclin-1, and ubiquitin-binding protein p62 mediate autophagy. The traditional Chinese medicine(TCM) treatment of DU mitigates clinical symptoms, accelerates ulcer wound healing, reduces ulcer recurrence, and delays further deterioration of DU. Furthermore, under the guidance of syndrome differentiation and treatment and the overall concept, TCM treatment harmonizes yin and yang, ameliorates TCM syndrome, and treats underlying diseases, thereby curing DU from the root. Therefore, this article reviews the role of autophagy and major related factors LC3, Beclin-1, and p62 in the healing of DU wounds and the intervention of TCM, aiming to provide reference for the clinical treatment of DU wounds and subsequent in-depth studies.

Cognition about emergency management of avulsed incisor in children among dentists in Guangdong province / 华西口腔医学杂志

OBJECTIVES@#This study aimed to evaluate and analyze the current situation of dentists in Guangdong pro-vince regarding the management of avulsed incisors, thereby providing a reference for making treatment strategies for avulsed incisors in the future.@*METHODS@#A total of 712 dentists with different educational backgrounds and working conditions in Guangdong province were randomly selected to conduct an online questionnaire survey on the cognition of children with avulsed incisors from April 2022 to May 2022. The data were recorded by Excel software and statistics were analyzed on Stata/SE 15.1.@*RESULTS@#A total of 712 dentists were investigated and 701 questionnaires were collected (98.46%). In addition, 65.9% of investigators came from the Department of Stomatology in a First-class Hospital or Stomatological Hospital. The results showed that the average number of avulsed teeth consulted by dentists was less than 20 per year. Although 99.7% of respondents considered normal saline as a suitable storage medium, 3.1% and 23.8% of them had a misunderstanding that the tap/alcohol could be used for root cleaning. Moreover, 93.4% was the correct selection rate of the treatment plan for processing on root surfaces before replanting by investigators. The correct selection rate of the duration using elastic fixation was only 10.7%. Meanwhile, 42.9% of investigators refused to inoculate tetanus immunoglobulin after teeth replanting. Emergency management of dental avulsion (EM) and clinical management of dental avulsion (CM) answered correctly with average scores of 14.60±11.85 and 14.48±2.67, respectively. Multivariate linear regression analysis revealed that working years were negatively correlated with EM and CM scores (P<0.05). There was a positive correlation between CM and EM scores with the number of avulsion cases treated by physicians each year (P<0.05). In terms of the EM score of dentists' learning attitude, investigators who had received enough knowledge were higher than those who had not and insufficient knowledge reserved, and the difference was statistically significant (P<0.05). The scores of investigators who thought they had a certain degree of knowledge about dental trauma were higher than those who thought they "did not understand", and the difference was statistically significant (P<0.05). In terms of CM scores, investigators who thought the knowledge of dental trauma was "very helpful" had higher scores than those who thought it was "not helpful", and the difference was statistically significant (P<0.05). The scores of the investigators who thought they had "relatively sufficient knowledge" of dental trauma were higher than those who thought they had "no knowledge" or "insufficient know-ledge", and the difference was statistically significant (P<0.05).@*CONCLUSIONS@#The overall accuracy of the management of avulsed incisors among dentists was low in Guangdong province. Dentists were more likely to have a higher rate of accuracy choice in treatment options for luxation injury and avulsion to enhance the prognosis of replanted teeth.

A case of systemic juvenile idiopathic arthritis with an early manifestation of pulmonary ground-glass opacities combined with macrophage activation syndrome / 中国综合临床

Systemic juvenile idiopathic arthritis is one of the common rheumatic and immune diseases in children. It has a sudden onset, obvious systemic symptoms, and lung involvement. However, systemic juvenile idiopathic arthritis with an early manifestation of pulmonary ground-glass opacities combined with macrophage activation syndrome is rare. The clinical data of a child with systemic juvenile idiopathic arthritis with pulmonary ground-glass shadow and macrophage activation syndrome who was admitted to Hubei Maternal and Child Health Care Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology in December 2021 were analyzed retrospectively in order to improve the understanding of rheumatic diseases and pulmonary lesions. The child was admitted to the hospital for 10 days due to rash and fever. Thoracic CT showed scattered ground glass like shadows in both lungs due to the prevention and control screening of COVID-19 pneumonia epidemic situation. After admission, the child was still repeatedly flaccid with high fever, accompanied by dysfunction of both lower limbs. The knee joint MRI found that there was synovitis in the knee joint, and various laboratory indicators suggested macrophage activation syndrome. After that, systemic juvenile idiopathic arthritis was diagnosed. After being treated with methylprednisolone, cyclosporine and topzumab, the clinical remission and the ground-glass shadow of the lung basically disappeared. Through the analysis of this case, it is suggested that clinicians should not ignore other diseases that cause ground glass shadow in the lung during the current epidemic of COVID-19.

Study on bioequivalence evaluation of dexamethasone acetate tablets in Chinese healthy volunteers / 中国临床药理学与治疗学

AIM: To assess the bioequivalence of oral dexamethasone acetate tablets between the test and reference formulations in healthy adult Chinese subjects on an empty stomach and after meals. METHODS: A randomized, open, single-dose, two-cycle double crossover bioequivalence study was followed. Twenty-four healthy subjects were included in the fasting group, and 32 healthy subjects were included in the postprandial group, taking 2 tablets (0.75 mg/tablet) of the test formulation (T) or 3 tablets (0.50 mg/tablet) of the reference formulation (R) per cycle for two cycles. The concentrations of dexamethasone acetate in human plasma were determined using liquid chromatography-mass spectrometry, and the pharmacokinetic parameters were calculated according to the non-atrial model using WinNonlin 8.0 software.The bioequivalence of both the test formulation and the reference formulation was evaluated. RESULTS: The pharmacokinetic parameters after oral administration of dexamethasone acetate tablets in a fasted state in subjects with the reference formulation are as follows: Tmax 1.13 (0.50, 4.00) and 1.00 (0.50, 5.00) h, AUC0-t (72.25±21.55) and (69.23±17.76) ng · mL

Mechanism of Huangqintang in Alleviating Side Effect of Chemotherapy for Endometrial Cancer Based on Network Pharmacology and Molecular Docking / 中国实验方剂学杂志

ObjectiveTo evaluate the utility and mechanism of Huangqintang combined with carboplatin in chemotherapy of endometrial cancer by experiments as well as network pharmacology and molecular docking. MethodThe xenograft model of endometrial carcinoma was induced in BALB/c nude mice. When the tumor volume reached about 100 mm3，24 nude mice were randomly assigned into a model group， a Huangqintang group （3.5 g·kg-1），a carboplatin group （50 mg·kg-1），and a combination group （3.5 g·kg-1 Huangqintang + 50 mg·kg-1 carboplatin）， with six mice in each group. The mice in the model group received 200 μL of normal saline by gavage， twice a day. The volume of the tumor and the body weight of the mice were measured every two days. After drug intervention for 20 days， the blood of the mice was collected for renal function and blood routine tests. Then the nude mice were euthanized and the tumor was weighted. In combination with the experimental results，the underlying mechanism of Huangqintang combined carboplatin was predicted through network pharmacology and the binding sites of active components were predicted by molecular docking. ResultThe tumor inhibition rates of the Huangqintang group，the carboplatin group， and the combination group were 8.87%，50.33% （P<0.05），and 64.66% （P<0.01），respectively. Compared with the results in the model group，the body weight，leukocyte，erythrocyte， and hemoglobin in the carboplatin group decreased，and creatinine and uric acid increased （P<0.05）. Compared with the carboplatin group，the combination group showed increased body weight，leukocyte， and hemoglobin （P<0.05），and decreased creatinine and uric acid （P<0.05）. A total of 114 potential active components of Huangqintang involved 200 targets related to the side effects of carboplatin. The core genes involved were mainly heat shock protein 90AA1 （HSP90AA1），transcription factor c-Jun （JUN）， and mitogen-activated protein kinase （MAPK）. Molecular docking showed that baicalein and wogonin could form a stable protein complex with HSP90AA1， serving as potential active molecules. Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis revealed that it might be related to the regulation of tumor necrosis factor（TNF） signaling pathway，interleukin（IL）-17 signaling pathway， MAPK signaling pathway， and toll-like receptor pathway. ConclusionHuangqintang has no obvious inhibitory effect on endometrial cancer，and the tumor suppression effect is not significantly enhanced after combination with carboplatin，but Huangqintang can alleviate carboplatin-induced side effects. The mechanism may be related to the complex network of Chinese medicine.

Molecular Mechanism of Resveratrol Against NAFLD Based on Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo predict the molecular mechanism of resveratrol against non-alcoholic fatty liver disease （NAFLD） based on network pharmacology and molecular docking and verify the results on the liver cell model induced by PM2.5 exposure. MethodThe targets of resveratrol were screened out from Traditional Chinese Medicine System Pharmacology Database and Analysis Platform （TCMSP）， PubChem， DrugBank， and SwissTargetPrediction， and the potential targets of NAFLD were retrieved from Comparative Toxicogenomics Database （CTD）， DisGeNET， GeneCards， and Online Mendelian Inheritance in Man （OMIM）. Then the common targets were obtained. STRING 11.5 was used to construct the protein-protein interaction （PPI） network of the common targets. Cytoscape 3.8.2 was used to plot the “target-pathway” network， and the core modules and key targets were selected. Metascape was adopted for Gene Ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analyses of common targets. SYBYL-X 2.0 was used for molecular docking of resveratrol to key targets. Finally，cell apoptosis and the expression of apoptosis-related proteins were detected by flow cytometry and Western blot in the PM2.5-exposed human liver cell line （HepG2）. ResultA total of 115 common targets of resveratrol and NAFLD were obtained. The key targets included tumor necrosis factor （TNF）， B-cell lymphoma-2 （Bcl-2）， and cysteinyl aspartate-specific protease-3（Caspase-3）. As revealed by KEGG enrichment analysis， 174 signaling pathways， represented by the apoptosis and TNF signaling pathways， were obtained. Molecular docking results showed that resveratrol had strong binding activities to Bcl-2 and Caspase-3. Furthermore，the results of flow cytometry and Western blot demonstrated that resveratrol inhibited cell apoptosis of PM2.5-exposed HepG2 cells by regulating the protein expression of Bcl-2 and Caspase-3. ConclusionResveratrol can treat NAFLD in a multi-pathway and multi-target way. It mainly inhibits liver cell apoptosis by affecting the expression of Bcl-2 and Caspase-3， which provides a theoretical basis for the follow-up research on the anti-NAFLD mechanism of resveratrol.

Therapeutic Effects of Mind-tranquilizing Chinese Medicines on Sleep-disorders by Regulating Energy Metabolism： A Review / 中国实验方剂学杂志

Sleep plays an important role in energy balance. As reported， sleep disorder is an important risk factor for metabolic diseases. Controlling the relationship between energy metabolism and sleep can affect sleep homeostasis and body metabolic rate. Chinese medicine， with remarkable curative effects in the prevention and treatment of insomnia， has the characteristics of green， safety， and few side effects， and attracts extensive attention of scholars in the world. In recent years， remarkable progress has been made in the research on the mechanism of Chinese medicine in interfering with sleep. This paper reviewed the research progress of mind-tranquilizing Chinese medicines， such as compounds （pterostilbene）， Chinese medicinal drugs （Ziziphi Spinosae Semen）， and Chinese medicinal prescriptions （Jiaotaiwan， Suanzaoren tang， Tianwang Buxindan， Anmeidan， Banxia Houpotang， Qihuo decoction， Songyu Anshen prescriptions， and Shuxie Yihao prescriptions） in the treatment of sleep disorders by regulating energy metabolism. The findings revealed that Chinese medicine can intervene in the sleep deprivation model by affecting metabolism-related pathways such as material metabolism， mitochondrial function， oxidative stress and inflammatory response， appetite system， and biological clock system. In terms of frequency of use， the top drugs are Ziziphi Spinosae Semen， Poria， Schisandrae Chinensis Fructus， and Salviae Miltiorrhizae Radix et Rhizoma which affect heart and liver meridians to regulate blood circulation， ensure energy supply， and play the role of nourishing the heart and tranquilizing the mind. The present paper summarized the effects and mechanisms of Chinese medicine in the treatment of insomnia and other sleep disorders from the perspective of energy metabolism to provide references for further research and exploration of diseases in the future.

Anmeidan Modulates Circadian Rhythm of Spontaneous Activity and Influences Clock Proteins in Sleep-deprived Rats / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Anmeidan （AMD） on biological rhythm and related protein expression in sleep-deprived rats. MethodA total of 80 SD rats were randomized into control group （Ctrl， equivalent volume of saline）， model group （SD， equivalent volume of saline）， AMD group （9.09 g·kg-1·d-1）， and melatonin group （MT， 0.27 g·kg-1·d-1）. Insomnia was induced in rats by self-made sleep deprivation box （4 weeks）. Circadian rhythm of spontaneous activity was evaluated by spontaneous activity video analysis system. Morphology of hypothalamus was observed based on hematoxylin-eosin （HE） staining， and the histomorphology of hypothalamus neurons and the Nissl's bodies based on Nissl staining. Western blotting was employed to detect the expression of hypothalamic proteins in cAMP-response element binding protein （CREB）/clock gene period （Per） pathway， and immunohistochemistry the expression of brain and muscle ARNT-like protein 1 （Bmal1）， Clock， Per1， and cryptochrome circadian regulator 1 （Cry1）. ResultThe model group demonstrated circadian rhythm disorder， as manifested by the significant increase in activity time in 6 designated time periods compared with the control group， and the rise in the activity speed and frequency （P<0.01）. Moreover， model group showed decrease in number of neurons which were sparsely arranged with shrunken or fragmented nuclei， reduction in number and loss of Nissl's bodies with light color， and drop in the relative expression of p-CREB and Per1， and the positive rate of Bmal1， Clock， Per1， and Cry1 （P<0.01）. Compared with model group， AMD group demonstrated reduction in time， speed， and frequency of activity （P<0.01）. Moreover， the AMD group also showed alleviation of neuronal damage （P<0.01）， and increase in the number of neurons with clear nuclei and cytoplasm in some， and the number of Nissl's bodies. AMD raised the expression of p-CREB and Per1 proteins， and the positive rate of Bmal1， Clock， Per1， and Cry1 （P<0.01）. ConclusionAMD ameliorated spontaneous circadian rhythm of sleep-deprived rats by regulating CREB/Per signaling pathway and further increasing the expression of Bmal1， Clock， Per1， and Cry1.

Protective Effects of Anmeidan on Cell Structure Against Neuronal Damage in Hippocampal CA1 Region of Sleep-deprived Rats / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Anmeidan （AMD） on neuronal structure and neuronal marker protein expression in the hippocampal CA1 region of sleep-deprived （SD） rats. MethodRats were randomly divided into control group， model group， an AMD group （9.09 g·kg-1·d-1）， and melatonin group （0.27 g·kg-1·d-1）. Rats in the control group and the model group received equal volumes of physiologicol saline. The SD model was induced by the self-made sleep deprivation box for four weeks. Ethovision XT system detected and analyzed the spontaneous behaviors of rats. The histomorphology of neurons in the hippocampal CA1 region was observed by hematoxylin-eosin （HE） staining and Nissl staining， and the changes in Nissl bodies were observed by Nissl staining. The ultrastructure of hippocampal cells was observed by transmission electron microscopy （TEM）. Immunohistochemistry was used to detect the expression of glial fibrillary acidic protein （GFAP）， microtubule-associated protein 2 （MAP2）， nestin， and neuronal nuclei （NeuN） in the CA1 region. ResultCompared with the control group， the model group showed longer distance， increased average activity speed， cumulative duration， average body fill， and higher activity frequency （P<0.01）. Besides， the neurons in the CA1 region were reduced in number with disorganized arrangement， wrinkled nuclei， deeply stained cytoplasm， reduced Nissl bodies， swollen and deformed mitochondria， shortened cristae， and swollen Golgi vesicles. Furthermore， the mean integral absorbance （IA） value of GFAP increased and those of MAP2， nestin， and NeuN decreased （P<0.01）. Compared with the model group， the AMD group showed shortened distance traveled， lower average activity speed， shorter cumulative duration， decreased average body fill， and reduced activity frequency （P<0.05， P<0.01）. Moreover， the neurons in the CA1 region were relieved from damage with increased cell number， clear nuclei and cytoplasm， increased Nissl bodies， and relieved mitochondrial damage. The IA value of GFAP decreased and those of MAP2， nestin， and NeuN increased （P<0.05， P<0.01）. ConclusionAMD can improve structural damage of neurons in the hippocampal CA1 region of sleep-deprived rats， which may be achieved by decreasing GFAP expression and increasing MAP2， nestin， and NeuN expression.

Effect of lipopolysaccharide-stimulated exosomes from human dental pulp stem cells combined with stromal cell-derived factor-1 on dental pulp regeneration / 中华口腔医学杂志

Objective: To investigate the effect of exosomes from mild-inflammation- stimulated human dental pulp stem cells (hDPSC) combined with stromal cell-derived factor-1 (SDF-1) on dental pulp regeneration in rats. Methods: Primary hDPSCs were isolated, cultured and then stimulated by using lipopolysaccharide (LPS). The exosomes from the hDPSCs with (L-EXO) or without (N-EXO) LPS were extracted by overspeed differential centrifugation and were identified by transmission electron microscopy and Western blotting. Forty SD rats, aged 6-8 weeks, were equally divided into S group (SDF-1 alone), L+S group (L-EXO combined with SDF-1), N+S group (N-EXO combined with SDF-1) and blank control group (no substance implanted into the root canal) by random number table method. Bilateral mandibular first molars were used as the experimental teeth to establish pulpless root canal models and different contents were implanted into the root canals according to the groups. All rats were over-anesthetized and sacrificed at the 30th day after content implantation. Bilateral mandibular tissues were taken for histological evaluation by means of HE, Masson and immunohistochemical stainings. Results: The HE staining showed new pulp-like tissue in the root canals of all three experimental groups. The amount of new tissues and the number of cells in the tissues were greatest in L+S group and least in S group. Masson staining showed that the mineralized tissue in L+S group was arranged longitudinally along the root canal wall and the collagen fibers were arranged in an orderly fashion, while those in N+S group showed an irregular and disordered distribution. Quantitative analysis of the area of neovascularization in each group showed that the density of vessels in the L+S group [(2.03±0.65)%] was significantly higher than that in the S group [(0.65±0.05)%] and the N+S group [(1.06±0.38)%] respectively (F=5.879, P<0.05). Immunohistochemical staining showed that the expression of CXC chemokine receptor 4 (CXCR4) was significantly lower in S and L+S groups than in N+S group, with a statistically significant difference (F=8.633, P<0.01). Conclusions: Exosomes secreted by hDPSCs combined with SDF-1 might increase the amount of new tissue in the root canal and the density of blood vessels in the tissue. L-EXO showed a stronger effect than N-EXO did. The combination of L-EXO with SDF-1 might result in more regular arrangement of mineralized tissue and collagen fibers in the regenerative tissues.

Effects of intermittent theta-burst stimulation on functional connectivity in patients with mild cognitive impairment / 中华行为医学与脑科学杂志

Objective:To investigate the effects of single intermittent theta-burst stimulation on functional connectivity in patients with mild cognitive impairment(MCI).Methods:From July to November 2020, forty MCI patients were selected and randomly divided into iTBS true stimulation group and iTBS sham-stimulation group, with 20 patients in each group.iTBS targeted the left dorsolateral prefrontal cortex (DLPFC). Montreal cognitive assessment (MoCA), mini-mental state examination (MMSE), activity of daily living scale(ADL), Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA) were evaluated at baseline.The resting state electroencephalography (rsEEG) was collected for 5 minutes before and after iTBS in the two groups.The phase lag index(PLI) of EEG functional connectivity was calculated, and the functional connectivity matrix diagram was drawn.SPSS 26.0 software was used for statistical analysis.Data were statistically analyzed by χ2 test, Wilcoxon rank sum test and independent sample t-test. Results:There were no significant differences in scores of MoCA, ADL, HAMD and HAMA between the two groups(all P>0.05). In the iTBS true stimulation group, compared with that before iTBS treatment(0.140(0.133, 0.144)), the PLI of β band increased significantly after iTBS treatment(0.146(0.136, 0.167))( P<0.05). The region of increased PLI was mainly concentrated in the central region(C3/C4-T7/T8). Compared with that before iTBS treatment(0.251(0.232, 0.299)), the PLI of α band increased after iTBS treatment(0.286(0.241, 0.359)), but the difference was not statistically significant( P>0.05). Conclusion:Single iTBS treatment can significantly increase the EEG functional connectivity in patients with MCI, indicating that iTBS targeting the left DLPFC can effectively regulate the EEG functional connectivity in patients with MCI, which may reveal the mechanism of iTBS in improving cognitive function in patients with MCI.

Effects of empathy nursing on negative emotion, sleep quality and health literacy of home treatment patients with pulmonary tuberculosis / 中国实用护理杂志

Objective:To explore the effect of empathy nursing intervention on negative emotion, sleep quality and health literacy of patients with pulmonary tuberculosis.Methods:A total of 77 patients in Department of Infectious Diseases of People′s Hospital of Leshan from June 2019 to September 2020 were divided into intervention group ( n=39) and control group ( n=38) by random digits table method. The patients in the control group were given routine nursing, and the patients in the intervention group were given empathy nursing intervention on the basis of routine nursing. Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI) and Health Literacy Management Scale (HeLMS) were used before and 12 weeks after intervention to evaluate the effects. Results:There was no significant difference in the total scores of HAMD, HAMA, PSQI and HeLMS between the two groups before intervention ( P>0.05), but after intervention, the scores of HAMD and HAMA in the intervention group were 10.64 ± 1.86, 12.64 ± 2.12, lower than those in the control group (14.63 ± 2.19, 15.11 ± 2.71). The differences were statistically significant ( t=-8.63, -4.46, P<0.05). The total score of PSQI and the scores of daytime dysfunction, use of hypnotic drugs, time of falling asleep, time of sleep, sleep quality, sleep disorder and sleep efficiency in the intervention group were 10.26 ± 1.65, 1.22 ± 0.22, 1.48 ± 0.23, 1.51 ± 0.27, 1.45 ± 0.26, 1.57 ± 0.22, 1.54 ± 0.21,1.49 ± 0.24, lower than those in the control group (13.07 ± 2.14, 1.92 ± 0.31, 1.75 ± 0.34, 1.95 ± 0.29, 2.02 ± 0.33, 1.84 ± 0.31, 1.72 ± 0.27, 1.87 ± 0.29). The differences were statistically significant ( t values were -11.45--3.27, all P<0.05). The total score of HeLMS and the scores of information acquisition, communication and interaction, and health improvement intention in the intervention group were 96.12 ± 14.71, 37.87 ± 5.83, 35.91 ± 5.13, 16.21 ± 2.53, higher than those in the control group (86.35 ± 14.12, 33.17 ± 5.27, 32.87 ± 5.42, 14.16 ± 2.19). The differences were statistically significant ( t values were 2.53-3.80, all P<0.05). Conclusions:Empathy nursing intervention can effectively alleviate the negative emotions of pulmonary tuberculosis patients, improve their sleep quality, and improve their health literacy level.

Microenvironmental stiffness mediates cytoskeleton re-organization in chondrocytes through laminin-FAK mechanotransduction / 国际口腔科学杂志·英文版

Microenvironmental biophysical factors play a fundamental role in controlling cell behaviors including cell morphology, proliferation, adhesion and differentiation, and even determining the cell fate. Cells are able to actively sense the surrounding mechanical microenvironment and change their cellular morphology to adapt to it. Although cell morphological changes have been considered to be the first and most important step in the interaction between cells and their mechanical microenvironment, their regulatory network is not completely clear. In the current study, we generated silicon-based elastomer polydimethylsiloxane (PDMS) substrates with stiff (15:1, PDMS elastomer vs. curing agent) and soft (45:1) stiffnesses, which showed the Young's moduli of ~450 kPa and 46 kPa, respectively, and elucidated a new path in cytoskeleton re-organization in chondrocytes in response to changed substrate stiffnesses by characterizing the axis shift from the secreted extracellular protein laminin β1, focal adhesion complex protein FAK to microfilament bundling. We first showed the cellular cytoskeleton changes in chondrocytes by characterizing the cell spreading area and cellular synapses. We then found the changes of secreted extracellular linkage protein, laminin β1, and focal adhesion complex protein, FAK, in chondrocytes in response to different substrate stiffnesses. These two proteins were shown to be directly interacted by Co-IP and colocalization. We next showed that impact of FAK on the cytoskeleton organization by showing the changes of microfilament bundles and found the potential intermediate regulators. Taking together, this modulation axis of laminin β1-FAK-microfilament could enlarge our understanding about the interdependence among mechanosensing, mechanotransduction, and cytoskeleton re-organization.

Progress on correlation between intestinal flora and mental diseases / 中国药理学通报

The impact of intestinal flora on human and animal health and diseases has attracted much attention both at home and abroad in recent years. The intestinal flora constitutes the intestinal microecosystem and plays an important role in physiological activities such as nutrition, metabolism, growth and development, barrier protection, and immunity. In this article, the relationship between intestinal dysbiosis and psychiatric diseases has been reviewed from two aspects:metagenomic characterization of intestinal microflora diversity in neurological diseases and validation of the relationship between intestinal flora and psychiatric diseases by fecal bacteria transplantation in germ-free mice. In addition, the microbial-gut-brain axis theory has been proposed in recent years, which links the nerve-endocrine-immune system to form a two-way signaling pathway. Intestinal flora plays an important role in regulating the central nervous system by promoting neurotransmitter release, endocrine, and immunity. The system plays an important role. Changes in intestinal flora mainly affect the host's nervous system through vagus nerve pathways, endocrine pathways, immune pathways, etc, thereby triggering or aggravating depression, autism, Alzheimer's disease, schizophrenia, Parkinson's disease, etc. This article reviews the relationships between host-related neurological abnormalities, intestinal flora imbalance and mental diseases, and discusses the research methods, research progress, and mechanism of the correlation between intestinal flora imbalance and mental diseases to research progress on microbe-gut-brain axis.

Effect of malleostapedotomy procedure on 17 cases of congenital middle ear malformation / 中华耳鼻咽喉头颈外科杂志

Objective: To conclude the clinical features and the postoperative efficacy of congenital middle ear malformation treated with Malleostapedotomy (MS), and to explore the security and effectiveness of MS surgery. Methods: The clinical data of 17 patients (18 ears) with congenital middle ear malformation undergoing MS procedure were analyzed. There were 10 males (11 ears) and 7 females (7 ears), aged from 7 to 48 years. The imaging examination, pure-tone audiometry, intraoperative findings and postoperative hearing improvement of these patients were analyzed and summarized, and software SPSS23.0 was used for statistical analysis. Rusults All the 17 patients (18 ears) presented with hearing loss since childhood on the affected sides. Preoperative high resolution CT (HRCT) of the temporal bone revealed definite malformations in 9 ears (6 ears with incus long process dysplasia and 3 ears with anterior and posterior crus dysplasia). Before surgery, the mean bone conductive hearing threshold at 500, 1 000, 2 000 and 4 000 Hz was (15.6±10.2) dB HL, the mean air conductive hearing threshold was (60.6±9.7) dB HL, and the mean air-bone gap was (45.0±8.9) dB. During the surgery, all 18 ears were found to be accompanied by absence or hypoplasia of incus long process. 12 ears had stapes fixation, 6 ears had oval window atresia. All patients were treated with MS procedure by using Piston. The patients were followed up for 3 months to 1 year. The mean bone conductive hearing threshold was (14.7±8.8) dB HL. The mean air conductive hearing threshold was (37.7±11.6) dB HL, and the mean air-bone gap was (23.0±8.0) dB. There were statistically significant differences in the mean air conductive hearing threshold and mean air-bone gap before and after surgery (P<0.05). While there were no statistically significant differences in the mean bone conductive hearing threshold before and after surgery (P=0.550). Conclusions: MS procedure is safe and reliable in patients with congenital middle ear malformation of incus long process dysplasia, stapes fixation or oval window atresia. HRCT is useful in evaluating the major deformity of ossicular chain and facial nerve deformity. However, it is not enough to evaluate the joint of incus-stapes and oval window atresia. MS surgery in middle ear malformation requires advanced surgical experience and skills. The hearing improvement can be significant, even though some air-bone gap after surgery exist.