The blood-brain barrier (BBB) is a special structure in the central nervous system (CNS), whose delicate properties can protect the brain from the attack by harmful large molecules and organisms within blood circulation. However, the very barrier also prevents the brain-targeted drugs from taking effects, posing great challenge to the treatment of neurodegenerative diseases, glioma and other brain diseases. With the development of nanotechnology, more and more nanoparticles (NPs) has been developed as a drug carrier, which can facilitate the drug with various mechanisms to get across the BBB. This article starts with introduction of the BBB, explaining the complexity of BBB structure and its unique features to form barriers, so that we can understand the difficulty in transporting drug into the BBB and the potential methods of targeting and permeate the barrier. Next, we focus on three main types of NPs that have been applied in the brain-targeted drug delivery system: polymeric-based NPs; biomimetic-based NPs and inorganic-based NPs. Furthermore, we deal with the specific NPs drug delivery strategies, which include absorption-mediated, carrier-mediated and receptor-mediated transcytosis. At the end of the article, we talk about the leading trend and future development of the brain-targeted nanoparticle drug delivery systems.

Core-shell tecto dendrimers (CSTDs) are a kind of superstructured dendrimeric nanoconstructs with relatively high-generation dendrimers as the cores and low-generation dendrimers as the shells. Recently, there is growing evidence that the performance of CSTDs constructed with poly(amidoamine) (PAMAM) dendrimers of different generations as reactive modules are not only superior to that of single-generation dendrimers, but also overcomes some biomedical limitations (e.g., restricted drug loading capacity, limited tumor passive targeting based on enhanced permeability and retention effect) of single-generation dendrimers. Herein, the design of CSTDs for biological imaging, chemotherapy, gene therapy, and combination therapy are reviewed. The current challenges and future development prospects of CSTDs in the field of biomedicine are also analyzed.

The health of the reproductive system is closely associated with females’ fertility ability and the quality of life. However, the incidence of diseases related to the female reproductive system has been increasing and the age of onset is becoming younger, generating numerous negative consequences on the female reproductive health. Therefore, there are urgent demands to develop effective therapeutic technologies and strategies. In recent years, the progress of tissue engineering and regenerative medicine has shown promising potentials of novel approaches for the treatment of related diseases by guiding tissue regeneration to restore the organs’ functions. In this article, we introduced the advances of scaffolds construction inspired by nanostructures and biomaterials as well as the applications in the premature ovarian failure, follicle culture in vitro, intrauterine adhesions, and the regeneration of defected uterine and pelvic organ prolapse. In addition, existing challenges and efforts that should be considered in the future were discussed.

Nanomaterials have the characteristics of small size and high specific surface area. These characteristics make it unique from other traditional materials in the properties of light, sound, electricity, heat, and magnetism. With the continuous development of nanomaterials and the needs of clinical medicine, more and more functionalized nanomaterials and related devices have been widely used in medical detection with the advantages of high sensitivity, high specificity, accuracy, and speed. The rapid development of nanomaterials can provide new methods for clinical diagnosis and provide more scientific basis for disease prevention and treatment. Nanomaterials have great development potential and broad application prospects in the diagnosis of a variety of diseases. In this article, the progress in the medical detection and diagnosis of infection, tumor, diabetes, neurodegenerative disease and cardiovascular diseases was reviewed; future perspectives were discussed as well.

Gene therapy based on nucleic acid drugs is the ultimate treatment technology for gene abnormality related diseases. However, nucleic acid drugs need the help of carriers to enter target cells and reach specific intracellular locations, therefore, the development of safe and efficient delivery systems for nucleic acid drugs is one of the fundamental technologies for gene therapy. Compared with viral vectors, non-viral vectors have higher safety, but are still facing the challenge of relative low transfection efficiency. With the advances of nanotechnology, the efficiency of non-viral carriers has been gained significantly improvements. In this paper, some representative nucleic acid-based drugs and vaccines were introduced, and the progresses of non-viral delivery carriers for uses in gene therapy have been reviewed.

Objective To investigate the genetic etiology of a patient with primary infertility and oocyte maturation defect. Methods Whole exome sequencing (WES) was carried out on patient's DNA to detect potential pathologic variants. The positive sites detected by WES were verified by Sanger sequencing, and the bioinformatic analysis of the mutation was analyzed. Results The patient was found to harbor compound heterozygous variants of the PATL2 gene in exon 15 c. 1374A>G (p. Ile458 Met) and c. 1289_1291delTCC (p. Leu430del), which were respectively inherited from her father and mother. Conclusions The compound heterozygous variation of PATL2 gene may be the genetic cause of infertility caused by the disturbance of oocyte maturation.

Objective To investigate the effects of MK886,a 5-LOX-activating protein(FLAP)inhibitor on the proliferation and apoptosis of human esophageal carcinoma cells KYSE-150 and TE-3,and to explore the possible mechanism.Methods KYSE-150 and TE-3 cells were treated with different concentrations of MK886(2.5,5,10,20,40 and 80μmol/L).Used xCELLigence RTCA monitor real-time the growth of cells to detect the half maximal inhibitory concentration(IC50)of MK886 in various cells.After the treatment with different concentrations of MK886,the expression levels of proteins with apoptosis and autophagy were detected by Western blotting,and cell cycle were detected by flow cytometry.Result MK886 decreased the proliferation of human esophageal carcinoma cells KYSE-150 and TE-3 (both P＜0.05).The IC50 values of MK886 in KYSE-150 is 29.11μmol/L,in TE-3 is 27.47μmol /L.The proportion of KYSE-150 and TE-3 cells treated with concentrations of MK-886 25μmol/L,G0/G1 phase were increased（both P＜0.001）however treated with concentrations of MK-886 50μmol/L,G2/M phase were increased(both P＜0.005). Did not detected the proteins expression levels of PARP, caspase-9 were increased with different concentrations of MK886.The expression levels of cleaved Caspase-3 and LC-3A/B-Ⅱwere detected increased with MK886 (both P＜0.001).Conclusion MK886 can inhibit the proliferation of KYSE-150 and TE-3 cells induce apoptosis and cell cycle,however autophagy induced by high concentrations MK886,provided the theoretical reference for clinical medication.

Objective To study the effects of Ｂalanophora polysaccharides (BPS) on the expression of BDNF and TrkB proteins and apoptosis-related proteins in rats with experimental liver injury induced by D-gal. Methods Rats were randomly divided into control group (control), D-gal (model, 200 mg /kg of hypodermic D- galactose), BPS low (BPS-L), medium (BPS-M), high (BPS-H) dose groups, which were treated with intragastric administration by 50, 100 and 200 mg/kg BPS per day, respectively. For six weeks in total, serum ALT and AST levels were measured by cardiac blood collection. HE staining was used to observe liver tissue morphology. The localization of BDNF and TrkB was determined by immunohistochemical staining. Western Blot was used to detect BDNF, TrkB, Bcl-2, Caspase-3 and Bax, protein expression. ELISA was used to determine the MDA content and SOD activity in liver tissues. Results Compared with the control group, the hepatocytes had edema and punctate necrosis in D-gal group, with increased serum ALT and AST levels (P <0.05), decreased SOD activity and increased MDA content (P <0.05), increased Bax, Caspase-3, BDNF, TrkB expression (P <0.05), decreased Bcl-2 expression (P <0.05). Compared to D-gal group, the hepatocyte degeneration and necrosis were obviously alleviated in BPS groups with each dose, with decreased serum ALT and AST levels (P <0.05), increased SOD activity and decreased MDA content (P <0.05), reduced B ax and Caspase-3 expression of pro-apoptotic proteins, increased expression Bcl-2 anti-apoptotic proteins (P <0.05), and decreased expression of BDNF and TrkB (P <0.05). Conclusions Balanophora polysaccharide had aprotective effect on experimental liver injury caused by D-gal. The mechanism may be related to the decrease of the expression of BDNF and TrkB and the decrease of hepatocyte apoptosis.

Objective: To explore the possible molecular mechanism of the interaction between Coxsackie virus Coxsackie virus group B type 5 (CVB5) and the host, the long non-coding RNA expression profile in human prototypic embryonal rhabdomyosarcoma cell line (RD) infected by CVB5 was investigated. Methods After 24 hours of RD cells infected with 1MOI CVB5 and extracted for RNA samples, and RNA-seq technology was used to obtain the differential expression profile of lncRNA in the cells, differentially expressed transcripts were analyzed by cluster analysis, GO analysis and KEGG pathway enrichment. At the same time, RNAfold was used to predict the secondary structure of lncRNA. Rusults Compared to the uninfected group, 1 754 mRNAs and 508 lncRNAs were up-regulated, and 3 106 mRNAs and 760 lncRNAs were down-regulated after CVB5 infection of RD cells. Co-expressed genes that differentially express lncRNA are mainly enriched in biological processes such as molecular structure activity, protein molecular binding, and humoral immune response; lncRNA targets are mainly involved in olfactory transduction pathway, cytokine-cytokine receptors interaction, neuroactive ligand-receptor interaction and other pathways. In addition, the seven differentially expressed lncRNAs verified by quantitative real-time PCR (RT-qPCR) are consistent with the sequencing results. Conclusions LncRNA is mainly involved in the regulation of the immune processes, which lays the foundation for a full understanding of the regulatory role of lncRNA in CVB5 infection .

Objective To investigate the effect of LINGO-1 shRNA (LV) and neurotrophic factors cocktail (NF，NFcocktail) encapsulated by Pluronic F-127（PF-127）hydrogel three-dimensional composite scaffolds on proliferation and differentiation of rat neural stem cells. Methods The LV was constructed and infected with NSCs at different MOI. RT-qPCR and Western blot were used to detect the expression of LINGO-1 in NSCs. BDNF NT-3 PDGF IGF-1 EGF bFGF and GDNF groups were divided into NFcocktail. The LV and NFcocktail were mixed with PF-127 and divided into different groups to culture NSCs. CCK-8 was used to detect the of cell viability of NSCs, the survival rate of NSCs was detected by LIVE/DEAD staining, and immunofluorescence staining was used to detect the proliferation and differentiation of NSCs. Results the optimal MOI for LV was 5. CCK-8 assay results showed that there was no significant difference in the survival rate of NSCs. The LIVE/DEAD and Nestin immune-fluorescence staining results showed that compared with control, the survival rate of NSCs and the proportion of neuron differentiation positive were the highest in PF-127+LV+NF group（P＜0.01）. Conclusions PF-127-LV-NFcocktail three-dimensional composite scaffold is beneficial to the proliferation and the directional differentiation of NSCs in rat.

Objective: To explore the expression of circRNA_23113 in lung adenocarcinoma and its influence on the proliferation and migration of lung adenocarcinoma cells. Methods: Screening 5 cases of lung adenocarcinoma and adjacent tissues by high-throughput sequencing,from which screened out the differentially expressed circular RNA circRNA_23113. Real-time fluorescence quantitative PCR was used to detect the expression of circRNA_23113 in lung adenocarcinoma tissues, serum and cells; the overexpression plasmid of circRNA_23113 was constructed, and its effect on cell proliferation and migration was analyzed by CCK-8 method, clone formation experiment, cell scratching and transwell chamber method; Westernblot was used to detect the expression of β-catenin, cyclinD1 and c-myc protein levels. Results: CircRNA_23113 was significantly lower expressed in tissues, serum and cells of patients with lung adenocarcinoma (P<0.05). Overexpression of circRNA_23113 inhibited the proliferation and migration of A549 and H1299 cells(P<0.05); circRNA_23113 inhibited the expression of β-catenin, cyclinD1 and c-myc(P<0.05). Conclusion:circRNA_23113 is poorly expressed in lung adenocarcinoma, and overexpression can inhibit the proliferation and migration of lung adenocarcinoma cells.

Objective To investigate the protective effect of SGK1 inhibitor GSK650394 on depressive behavior and hippocampal neurotrophy in depressive rats. Methods SD rats were randomly divided into control group, depression model group and GSK650394 group. Depression model was established by chronic mild unpredictable stress. The behavioral changes of the SD rats were observed by novel feeding test, forced swimming and 1% sugar consumption test. The changes of CORT and monoamine neurotransmitters in plasma and serum were observed by Elisa. The changes of BDNF, NT-3 and NGF in hippocampus were detected by Western-Blotting. Results Compared with the control group, sucrose preference decreased and swimming immobility time increased significantly (P < 0.01), EL and Lat.T prolonged significantly (P < 0.05 or P < 0.01), the content of CORT in plasma increased significantly (P < 0.01), the content of 5-HT, NE in serum and the expression of BDNF, NT-3, NGF in hippocampus was significant increased in the model group. Compared with model group, GSK650394 significantly increased sucrose preference, decreased immobility time (P < 0.05 or P < 0.01), shortened EL and Lat.T (P < 0.05), decreased the content of CORT in plasma (P < 0.01), increased the level of 5-HT and NE in serum (P < 0.01), promoted the expression of NT-3, BDNF and NGF in hippocampus. Conclusion SGK1 inhibitor can significantly relieve depression like behavior, which may be related to promoting neurotrophin.

Objective: To observe the effect of necroptosis inhibitor-1 （Nec-1） on glial scar formation in rats with spinal cord injury and explore its mechanism. Methods: The rats were randomly divided into sham operated group, model group and RIP1 K inhibitor Nec-1 group. After the spinal cord injury model group was successfully constructed, 0.9% sodium chloride solution and 10 μmol/L Nec-1 were injected into the lateral ventricles of the rats, respectively. In the sham operation group, rats only were opened the lamina and did not hit the spinal cord. At 1st,3rd,7th,14th day after operation, the motor function of the hind limbs was measured by BBB, the formation of glial scar was detected by immunofluorescence, and the expressions of CathepsinB, Caspase-3, GFAP and vimentin were detected by Western blot. Results: On the 14th day after operation, compared with the sham operation group, the BBB scores of the model group and Nec-1 group were significantly lower (P < 0.05), compared with the model group, the BBB score of Nec-1 group was significantly higher (P < 0.05). On the 14th day after operation, NF-200 fluorescence was not found in the sham operation group, but in the model group and Nec-1 group, compared with the model group, the intensity of NF-200 fluorescence labeling in Nec-1 group decreased significantly (P < 0.05). On the 7th and 14th day after operation, compared with the sham operation group, the protein levels of CathepsinB, Caspase-3, GFAP and vimentin in the model group and Nec-1 group were significantly higher (P < 0.05), compared with the model group, the protein levels of CathepsinB, Caspase-3, GFAP and vimentin in Nec-1 group decreased significantly (P < 0.05). Conclusions: Nec-1 may regulate CathepsinB-Caspase pathway, reduce the expressions of GFAP and vimentin proteins, reduce the formation of glial scar after spinal cord injury, and promote the recovery of neural function.

Objective: To investigate the effects of furosemide on PERK/eIF2α/CHOP pathway and secondary brain injury in rats with intracerebral hemorrhage (ICH). Methods: ICH rat model was established by intracerebral injection of collagenase type IV, and the rats were randomly divided into model group, low-dose furosemide group, medium dose furosemide group, high-dose furosemide group and ganglioside group, with eighteen rats in each group, another eighteen SD rats were selected as sham operation group. After drug treatment, the neurological deficits of rats in each group were scored; the water content of brain tissue was measured; Evans blue extravasation test was used to detect the blood-brain barrier injury; HE staining was used to detect the damage of hippocampal neurons; enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of interferon-γ (IFN-γ) and interleukin-6 (IL-6); Western blot was used to detect the expression of p-PERK/PERK, p-eIF2α/eIF2α and CHOP. Results: Compared with those in the sham operation group, the hippocampal neurons in the model group were degenerated and necrotic, the shrinkage was smaller, the number was significantly decreased, severe pathological damage was found, the neurological deficit score, brain water content, Evans blue exudation, levels of serum IFN-γ and IL-6, expression levels of p-PERK/PERK, p-eIF2α/eIF2α and CHOP were significantly increased (P < 0.05). Compared with those in the model group, the pathological damage of hippocampal neurons in the low, medium and high dose furosemide groups and ganglioside group were reduced, the neurological deficit score, brain water content, Evans blue exudation, levels of serum IFN-γ and IL-6, expression levels of p-PERK/PERK, p-eIF2α/eIF2α and CHOP were decreased (P < 0.05), furosemide groups were dose-dependent, and there was no significant change in each index between furosemide high-dose group and ganglioside group (P > 0.05). Conclusion: Furosemide can down-regulate the expression of PERK/eIF2α/CHOP pathway protein, relieve brain edema and hippocampal neuron damage, and repair the neural function of ICH rats.

Objective: To investigate the effects of eukaryotic elongation factor 2 kinase (eEF-2K) gene transfection and sodium tanshinone IIA sulfonate (STS) on proliferation, invasion and migration of lung adenocarcinoma A549 cells and its mechanism. Methods: After treated with 0, 1.25, 2.5, 5, 10 and 20 μg/mL STS for 48 h, the survival rate of A549 cells was detected by cell counting kit-8 (CCK-8) method to screen the concentration of STS. After siRNA targeting eEF-2K gene (siRNA-eEF-2K) was transfected into A549 cells, the expression levels of eEF-2K protein and mRNA in A549 cells were detected by Western blot and real-time quantitative PCR. A549 cells were divided into siRNA-NC group (transfected with siRNA-NC), siRNA-eEF-2K group (transfected with siRNA-eEF-2K), siRNA-NC + STS group (treated with 10 μg/mL STS after siRNA-NC) and siRNA-eEF-2K + STS group (treated with 10 μg/mL STS after siRNA-eEF-2K), the survival rate, clone formation rate, number of transmembrane cells, migration rate and apoptosis rate of A549 cells were detected by CCK-8 method, clone formation test, Transwell chamber test, scratch test and flow cytometry, the protein expression levels of protein kinase B (AKT), phosphorylation (p)-AKT, Ki67, matrix metalloproteinase-2 (MMP-2) and B-lymphoma-2 genes (Bcl-2) were detected by Western blot. Results: Compared with 0 μg/mL STS, the survival rate of A549 cells was significantly decreased after treatment with 1.25, 2.5, 5, 10 and 20 μg/mL STS (P < 0.05), and it was in a concentration dependent manner; the 50% inhibitory concentration of STS on A549 cells was 10.39 μg/mL. Transfection of siRNA-eEF-2K can successfully inhibit the expression of eEF-2K protein and mRNA in A549 cells. Compared with those in siRNA-NC group, the cell survival rate, clone formation rate, number of transmembrane cells, migration rate and p-AKT, Ki67, MMP-2 and Bcl-2 in proteins siRNA-eEF-2K + STS group were significantly lower, while the apoptosis rate was significantly higher (P < 0.05), the changes of the above indexes in siRNA-eEF-2K + STS group were significantly greater than those in siRNA-NC + STS group and siRNA-eEF-2K group. Conclusions: The eEF-2K gene silencing combined with STS can synergistically inhibit the proliferation, invasion and migration of A549 cells and promote cell apoptosis. The mechanism may be related to the inhibition of protein expression of p-AKT, Ki67, MMP-2 and Bcl-2.

Objective: To investigate the influence of propofol on the proliferation and apoptosis of endometrial cancer cells and the effect on mTOR/S6K1 signaling pathway. Methods: Human endometrial cancer cell line RL95-2 was divided into control group and propofol group. The control group was not intervened, and the propofol group was intervened with different concentrations of propofol. CCK-8 method was used to detect cell proliferation; clone formation assay was used to detect the ability of cell clone formation; flow cytometry was used to measure cell apoptosis; colorimetry was used to measure the activities of Caspase-3 and caspase-9; Western blot (WB) was used to detect the activation levels of protein kinase B (Akt), mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase 1 (S6K1). Results: Compared with those in the control group, the proliferation rate and colony forming ability of RL95-2 cells in propofol groups were significantly lower (P < 0.05), the apoptosis rate and the activities of Caspase-3 and caspase-9 were significantly higher (P < 0.05), the activation levels of Akt, mTOR and S6K1 were significantly lower (P < 0.05). Conclusion: Propofol may inhibit the proliferation and promote the apoptosis of endometrial cancer cells by regulating mTOR/S6K1 pathway.

Objective To investigate the effect of recombinant Treponema pallidum protein Tp47 (rTpp47) on the expression of uPA in THP-1 macrophages and on the permeability of vascular endothelial cells. Methods THP-1 cells were stimulated with rTpp47 for 24 hours and then the culture supernatant and THP-1 cells were collected respectively. The expression of Urokinase-type plasminogen activator (uPA) in THP-1 cells was detected by ELISA and Western blot. After THP-1 Cell culture supernatant was used to stimulate human umbilical vein endothelial cells (HUVEC) monolayers, FITC dextran was used to evaluate the permeability of HUVEC . Western blot method was used to observe the effect of uPA on the expression of tight junction protein claudin-5 in HUVEC cells and on the PKC signaling pathway in THP-1 cells stimulated by rTpp47.Results The synthesis and secretion of uPA in THP-1 cells stimulated by recombinant protein rTpp47 were significantly higher than those in the control group (P < 0.05). When HUVECS were stimulated by the THP-1 cell supernatant for 12 hours and 24 hours , the relative permeability of vascular endothelial cells in the experimental group was significantly higher than the control group (P < 0.05 for 12 hours and P < 0.0001 for 24 hours). Amiloride , the synthetic inhibitor of uPA, significantly inhibited the uPA expression and secretion of THP-1 cells stimulated by rTpp47 (P < 0.0001) and significantly suppressed PKC phosphorylation (P < 0.05) in THP-1 cells induced by rTpp47. Conclusion Our data indicate that the recombinant protein rTpp47 can stimulate the synthesis and secretion of uPA in THP-1 cells by activating PKC signaling pathway and uPA may increase the permeability of vascular endothelial cells.

Objective: To investigate the situation of Helicobacter pylori infection in healthy people and analyze the related risk factors. Methods: Retrospective analysis was conducted on 10661 healthy subjects who underwent carbon 13C-UBT on January 1, 2019 solstice and December 30, 2020 in the affiliated hospital of North Sichuan Medical College. According to the infection status of Helicobacter pylori (H.pylori), the subjects were divided into H.pylori positive group and H.pylori negative group. Analysis H.p ylori infection and platelets (PLT), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), T3, T4, TSH, pepsinogen Ⅰ, pepsinogen II, and gastric secretion, 17, homocysteine (Hcy), uric acid (UA), the relationship between the total bilirubin (TBIL). Results: 1. The total number of positive infections: 4382, the total positive rate: 41.10%, including 2717 male positive cases, the positive rate: 25.49%; There were 1665 cases of positive infection in females, and the positive rate was 15.62%, which was higher in males than in females (P<0.05). 2. H.p ylori compared to the positive and negative groups: positive age slightly higher than negative group (P < 0.05), H.p ylori positive group in BMI, systolic pressure, diastolic blood pressure, TG, FBG, pepsinogen Ⅰ, pepsinogen Ⅱ, G-17, Hcy were higher than negative group (P < 0.05); H.p ylori positive group in HDL - C, pepsinogen Ⅰ/Ⅱ, TBIL were lower than that of negative group (P < 0.05). There was no significant difference in PLT, UA, TC, LDL-C, T3, T4 and TSH between the two groups (P>0.05). 3, DOB value height and age, FBG, pepsinogen Ⅰ, pepsinogen Ⅱ, G - 17 were positively correlated (P = 0.000); DOB values with the pepsinogen Ⅰ / Ⅱ, TBIL negatively correlated (P = 0.000). 4, further P < 0.05 parameters into binary Lojistic regression analysis, the results showed that age, BMI, FBG, TBIL, pepsinogen Ⅰ, pepsinogen Ⅱ, pepsinogen Ⅰ / Ⅱ, Hcy are a risk factor for helicobacter pylori infection (P < 0.05). Conclusion: The risk of H.pylori infection increases with age, and infection is more common in males. Binary Lojistic regression analysis showed that age, BMI, FBG, TBIL, pepsinogen Ⅰ, pepsinogen Ⅱ, pepsinogen Ⅰ / Ⅱ, Hcy are H.p ylori the risk factors of infection. Early intervention of these risk factors is expected to reduce the infection of H.pylori and provide theoretical basis for the primary prevention of gastrointestinal diseases.

Objective To compare the setup errors provided by the chest and abdomen flat frame fixation device and integral cervicothoracic fixation device in supraclavicular regions of locally advanced esophageal cancer patients. Methods The cone beam computed tomography (CBCT) images of 50 locally advanced esophageal cancer patients who received radiotherapy in supraclavicular region were retrospectively analyzed. Each group of using the chest and abdomen flat frame fixation device (group A) or the integral cervicothoracic fixation device (group B) included 25 patients .There were 175 CBCT images in group A and 230 CBCT images in group B. The setup errors of the two groups were analyzed, and the movement and displacement of acromioclavicular joint in three-dimensions were measured. The differences were compared by independent sample t test and rank sum test. Results The setup errors were significant difference between group A and group B. The P value in X axis (left-right) and Z axis (anterior-posterior) both were less than 0.001 （P＜0.001）；The P value in pitch was less than 0.001 （P＜0.001），and roll was less than 0.05 （P＜0.05）. The movement amplitude of acromioclavicular joint (ΔX, ΔY, ΔZ) of groups A and B were (0.100.10)cm and (0.080.08)cm in X axis, (0.140.13)cm and (0.110.11)cm in Y axis, (0.160.12)cm and (0.110.12)cm in Z axis. The three-dimensional displacement of groups A and B were (0.270.14)cm and (0.200.14)cm, (P＜0.001). Conclusions When the influence of rotation angle is properly controlled, the application of the integral cervicothoracic fixation device is better to immobilize the acromioclavicular joint and reproduce the setup position for locally advanced esophageal cancer patients .Special attention should be paid for the influence of rotation angle on the location accuracy of target.

Objective To isolate and identify Rhodococcus equi （R.equi）from clinical specimens, and to explore the relationship between antibiotic sensitivity and clinical efficacy. Methods From April 2019 to April 2020, 17 cases of erythrococcus equi were isolated and identified as the treatment group, and 17 cases of empirical drug treatment patients as the control group. Results According to the antibiotic sensitivity combined with drug therapy, the clinical efficacy of the treatment group was higher than that of the control group. Conclusion Rational use of antibiotics combined with drugs can significantly improve the cure rate of clinical curative effect.

Objective To establish a molecular detection method for the Plasmodium female gametocyte. Methods Capture and ligation probes was specific designed based on Plasmodium falciparum and Plasmodium vivax femal gametocyte special RNA targets,which is s25 mRNA. After the whole blood is lysed, the RNA target is directly released and fixed on the 96-well plate with capture probes without extraction. Washing away the unbound probe, the ligation probes which also hybridized to the RNA target is specific ligated to form an single-strand amplification template with specific-designed sequence at both ends. The SYBR Green qPCR was carried out with universal primers and the TaqMan qPCR was carried out with universal primers and universal fluorescent probes. Evaluate the sensitivity, specificity and repeatability of this method and compared with the RT-qPCR methods. And it was also used to detect clinical samples. Results This method was successfully applied to detect s25 mRNA with high sensitivity and specificity. All three methods can detect as low as 11 copies of S25 mRNA targets, and this method is simpler than RT-qPCR. And it can accurately detect gametocytes in the blood of malaria patients. The detection of 96 samples can be completed within 3h. Conclusion Established a method for the femal gametocyte of Plasmodium falciparum and Plasmodium vivax detection which provides a sensitive and efficient method for large-scale disease screening of gametocytes and control of malaria transmission .

Schwann cells (SCs) have strong plasticity. After peripheral nerve injury, Schwann cells dedifferentiate into repair phenotype and dominate the repair process. C-Jun N-terminal kinase, mitogen activated protein kinase and other signaling pathways and transcriptional regulators are involved in regulating Schwann cell-mediated repair process. In this review, we discuss the main signaling pathways and transcriptional regulators of Schwann cell promoting peripheral nerve regeneration.

Liver barrier, the main structure to protect the liver from exogenous harmful substances, plays an important role in maintaining secretion function, regulating bile transport and intercellular information transmission. Liver barrier protein alteration and barrier dysfunction can be induced by endotoxin, inflammatory cytokines and bile acids, which may be involved in the occurrence of colitis-related liver diseases. To explore the effect and underlying mechanism of intestinal inflammation on liver barrier function may explain the pathogenesis of colitis-related liver diseases, and thus provide clues and basic information for its prevention and treatment.

Establishment of physiological reference intervals (RIs) is important for health status evaluation, disease screening and diagnosis,and the effect assessment of clinical therapy. Currently, there is no review on methodology of RI establishment in China. Therefore, by reviews of literatures on methodology of RI establishment, this study aimed to give a comprehensive description on the purpose and significance of RI establishment and its statistical methods of calculation, as well as its application. Three methods are commonly used for RI calculation: the nonparametric, parametric and robust estimate. Researchers could choose a specific method or methods based on their purpose and the characteristics of the data. This review could provide methodological reference for RI establishment in China, and also guidelines to better understand the meaning of physiological constant RIs in health practices.

IL-6/JAK/STAT3 is one of the most significant signaling pathways activated by IL-6.IL-6 and p-STAT3 are highly expressed in prostate cancer (PCa) tissues and metastatic tumors, and play a key role in inducing the occurrence of prostate cancer, promoting the proliferation, invasion and metastasis of tumor cells, and participating in castration resistance and tumor drug resistance of PCa through activation of AR.The multiple roles of IL-6/JAK/STAT3 and its activated downstream factors in tumor progression provide a good basis for the development of chemotherapy drugs. Currently, many targeted inhibitors have been proved to be effective in inhibiting tumor progression, and more effective drugs are expected to be developed.

Prostate cancer is a common malignancy in males. Exosomes are lipid bilayer vesicles containing protein, mRNA and miRNA, which are active in intercellular communications. Exosomes can promote the development of prostate cancer, support immune escape and chemotherapy resistance, stimulate angiogenesis, induce epithelial-mesenchymal transition of tumor cells, and contribute to the formation of pre-metastatic niche, thus promoting the invasion and metastasis of prostate cancer. Based on the role in tumor biological behavior and heterogeneity in different cells, exosomes hold great potentials as biomarker for diagnosis and prognosis of prostate cancer, and are expected to become a favorable drug carrier. It has a promising prospect for cancer therapy.

Screening high-quality gametes and high developmental potential embryos is focus of assisted reproductive technology. In recent years, studies have found that the embryo culture medium contains proteins secreted by the embryo, free DNA fragments, cytokines and so on, and the nutrients needed for embryo development are obtained from the culture medium. Through Using non-invasive methods, for example embryo metabonomics, proteomics, to analyzed the composition of the embryo culture medium. These biomarkers are helpful for rapid and accurate screening of high-quality embryos with the most developmental potential. This paper summarizes the effects of amino acids, carbohydrates, cytokines and proteins on embryonic development.

Pituitary adenomas (PAs) are the second most common primary central nervous system tumors. Although most PAs can be cured with surgery, medical treatment, or radiotherapy, some PAs recur, invade adjacent structures, or even metastasize to other organs after traditional treatments, reducing patient overall survival and their quality of life. In recent years, studies on the immune microenvironment of brain tumors emerged, especially in the field of glioma, providing potential effective treatment targets for immunotherapy and setting the foundation for improving patient survival. However, previous studies have only conducted preliminary analyses on immune cells, immune molecules, and cytokines in the microenvironment of PAs, and immunotherapy research of PAs in animal models and humans has just started.

Circular RNAs （circRNAs） are non-coding RNAs with unique covalently closed circular structures, which are widely found in eukaryotic cells. Recent studies have shown that circRNAs are involved in the pathophysiological processes of various diseases, including malignant tumors, by regulating microRNAs, binding to proteins, and regulating transcription and splicing processes. The special structure and complex functions of circRNAs make them have great research potential in the field of cancer. Prostate cancer is one of the most common malignancies among men in the world. At present, the pathogenesis and treatment of prostate cancer still need to be further studied.

Since the startup of the "group type" aid work for Tibet, five radiologists from Peking Union Medical College Hospital have been consecutively sent to work in the Radiology Department of People's Hospital of Tibet Autonomous Region. For the past five years, remarkable achievements have been made in the equipment and software upgrading, local staff online and offline education, research programs and paper publishing, and modern management rules and regulations establishment. In this paper, all of these would be summarized and some suggestions for the future are also discussed.

Objective To design an eye model that can simulate the fundus for teaching direct ophthalmoscopy and to evaluate its effectiveness. Methods We first used 3D printing materials to make an eye model, and then randomly assigned 92 undergraduates into two groups: group A (model training group) and group B (traditional training group). After the same training time, real patients were used to test the students, with 120 seconds as the examination time limit. We recorded the ability of the students to clearly see the optic disk, and the time to determine the cup-to-disk ratio and whether the students were correct. Results 43 students in group A (93.48%) successfully saw the fundus, while 21 students in group B (45.65%) saw the fundus. The difference between the two groups was 47.83%, and the 95% confidence interval was 29.59%-66.07%, P < 0.0001. The median time to see the fundus was 29s in group A; the 95% confidence interval was 23-45s. Based on the lower limit of the 95% confidence interval, it was estimated that a minimum of more than 80 seconds was required in group B. The P value of the log-rank test was < 0.0001, and group A was significantly faster than group B. Conclusion This 3D-printed eye model significantly improved the students' study interest, study efficiency and study results and is worthy of being promoted.

Objective To explore the teaching effect of mind mapping in implementing the teaching concept of " student-centered learning (SCL)"．Methods One hundred and eighteen undergraduates of four-year curriculum in Nursing School, Peking Union Medical College enrolled in 2019 were selected as objects. Before the learning of the human parasitology, the students were investigated on the "students' autonomous learning situation"; then they were guided to make up a mind map of what they need to learn in the course of human parasitology; and the effect of mind mapping were evaluated at the end of the course. Results The teaching method that guides students to make up a mind map can effectively stimulate students' enthusiasm for learning, significantly improve students' sense of self-confidence, promote students' deep understanding of what they have learned and the logic thinking of learning, thereby effectively improving students' autonomous learning capacity. Conclusions The application of mind mapping can effectively implement the "student-centered learning" concept.

Objective To explore the application effect of diversified teaching mode in ultrasound-guided pain interventional therapy. Methods Thirty learners who studied in the Department of Pain, Peking University Third Hospital from January 2018 to December 2020 were enrolled as participants, and were divided into control group and observation group. The control group adopted conventional teaching mode, while the observation group adopted diversified teaching mode. The clinical skill assessments, teaching quality and satisfaction scores of the two groups were compared. Results The excellent and good rate of clinical skill assessments in the observation group was 93.3%, which was higher than that in the control group , which was 73.3%(P<0.05). Scores of mastering basic theoretical knowledge, improving clinical thinking ability, motivating learning interests and improving disease diagnosis and treatment ability in observation group were higher than those in control group (P < 0.01). Conclusion Diversified teaching mode can promote the improvement of ultrasound-guided pain interventional therapy skills, and is helpful to improve learners' comprehensive clinical ability. It is a teaching mode that is worthy of reference.