Electroacupuncture Promotes Functional Recovery after Facial Nerve Injury in Rats by Regulating Autophagy via GDNF and PI3K/mTOR Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To explore the mechanism of electroacupuncture (EA) in promoting recovery of the facial function with the involvement of autophagy, glial cell line-derived neurotrophic factor (GDNF), and phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway.@*METHODS@#Seventy-two male Sprague-Dawley rats were randomly allocated into the control, sham-operated, facial nerve injury (FNI), EA, EA+3-methyladenine (3-MA), and EA+GDNF antagonist groups using a random number table, with 12 rats in each group. An FNI rat model was established with facial nerve crushing method. EA intervention was conducted at Dicang (ST 4), Jiache (ST 6), Yifeng (SJ 17), and Hegu (LI 4) acupoints for 2 weeks. The Simone's 10-Point Scale was utilized to monitor the recovery of facial function. The histopathological evaluation of facial nerves was performed using hematoxylin-eosin (HE) staining. The levels of Beclin-1, light chain 3 (LC3), and P62 were detected by immunohistochemistry (IHC), immunofluorescence, and reverse transcription-polymerase chain reaction, respectively. Additionally, IHC was also used to detect the levels of GDNF, Rai, PI3K, and mTOR.@*RESULTS@#The facial functional scores were significantly increased in the EA group than the FNI group (P<0.05 or P<0.01). HE staining showed nerve axons and myelin sheaths, which were destroyed immediately after the injury, were recovered with EA treatment. The expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats (P<0.01); however, EA treatment reversed these abnormal changes (P<0.01). Meanwhile, EA stimulation significantly increased the levels of GDNF, Rai, PI3K, and mTOR (P<0.01). After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist, the repair effect of EA on facial function was attenuated (P<0.05 or P<0.01).@*CONCLUSIONS@#EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of FNI. EA may exert this neuroreparative effect through mediating the release of GDNF, activating the PI3K/mTOR signaling pathway, and further regulating the autophagy of facial nerves.

Effect of electroacupuncture on enteric neuronal autophagy in functional constipation mice / 中国针灸

OBJECTIVES@#To explore the effect mechanism of electroacupuncture (EA) on functional constipation (FC) at the combined lower he-sea and front-mu points of large intestine based on enteric neuronal autophagy.@*METHODS@#A total of 40 SPF Kunming mice were randomly divided into 5 groups (n = 8), i.e. a control group, a model group, an acupuncture group, a 3-methyl adenine (3-MA) group, and a 3-MA + acupuncture group. Except the control group, the FC model was established by gavage with compound diphenoxylate suspension for 14 days in the other 4 groups. After successful modeling, the mice of the acupuncture group and the 3-MA + acupuncture group received EA at bilateral "Tianshu" (ST 25) and "Shangjuxu" (ST 37), stimulated for 30 min with disperse-dense wave, 2 Hz/15 Hz of frequency, 1 mA of intensity. EA was delivered once daily. One course of treatment was composed of 5 days and 2 courses were needed, with an interval of 2 days. An intraperitoneal injection of 3-MA (15 mg/kg) was administered 30 min before EA in the mice of the 3-MA group and the 3-MA + acupuncture group, once daily. Before and after intervention, the time of the first black stool defecation and defecation behaviors in 6 h were observed in each group. After intervention, in every group, the small intestine propulsion rate was calculated, the colon tissue morphology was observed using HE staining, the ultrastructure of enteric neuronal autophagy was observed under transmission electron microscope, and the expressions of microtubule-associated protein 1 light chain 3 (LC3), Beclin-1 and neuronal nuclear antigen protein (NeuN) in neurons of colonic muscularis were determined by immunohistochemistry.@*RESULTS@#Before intervention, when compared with those in the control group, the time of the first black stool defecation was prolonged (P<0.01, P<0.05), and numbers (P<0.01), wet weight (P<0.01, P<0.05) and water content (P<0.05, P<0.01) of stool in 6 h were reduced in the model, acupuncture, 3-MA and 3-MA + acupuncture groups. After intervention, compared with those in the control group, the time of the first black stool defecation was longer (P<0.05), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were decreased in the model group. The time of the first black stool defecation was shortened (P<0.01), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were increased in the acupuncture group when compared with those in the model group. The time of the first black stool defecation was extended (P<0.01), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were declined in the 3-MA + acupuncture group in comparison with those in the acupuncture group. All layers of colon tissue were normal and intact in each group. When compared with the control group, the small intestine propulsion rate and the average optical density (OD) values of LC3, Beclin-1 and NeuN in neurons of colonic muscularis were decreased (P<0.01), and autophagosomes were dropped in the model group. In the acupuncture group, the small intestine propulsion rate and the average OD values of NeuN, LC3 and Beclin-1 in neurons of colonic muscularis increased (P<0.01,P<0.05), and autophagosomes were elevated when compared with those in the model group. The small intestine propulsion rate and the average OD values of NeuN, LC3 and Beclin-1 in neurons of colonic muscularis were dropped (P<0.05,P<0.01) in the 3-MA + acupuncture group in comparison with those in the acupuncture group.@*CONCLUSIONS@#Electroacupuncture may promote enteric neuronal autophagy and increase the number of neurons so that the intestinal motility can be improved and constipation symptoms can be relieved in FC mice.

Chloroplast genome resolution and phylogenetic analysis of Ardisia crispa var. amplifolia and Ardisia crispa var. dielsii / 药学学报

italic>Ardisia crispa (Thunb.) A. DC. is a traditional Miao medicinal herb with significant therapeutic effects in the treatment of sore throat, tonsillitis, edema of nephritis and bruising and rheumatism, etc. Ardisia crispa var. amplifolia and Ardisia crispa var. dielsii are varieties of A. crispa. A. crispa var. amplifolia and A. crispa var. dielsii are controversial in terms of species evolutionary relationships and taxonomic identification. In this study, we sequenced the whole genome sequences of A. crispa var. amplifolia and A. crispa var. dielsii chloroplasts using Illumina platform, assembled, annotated and characterized them, compared the structural features and degree of variation among chloroplast genomes using bioinformatics methods, and also downloaded constructing phylogenetic trees to analyze the phylogenetic relationships of chloroplasts in Primulaceae and Myrsinaceae using whole genome sequence information. The results showed that the complete chloroplast genome sequences of A. crispa var. amplifolia and A. crispa var. dielsii were 156 749 bp and 156 748 bp in length, with 132 genes annotated, including 87 protein-coding genes; the codon preference of A/U was greater than that of G/C; The differences in the coding regions of rps15 and rpoB genes in the comparative genome analysis can be used as loci for molecular identification of the two species; the differences in the coding regions of ycf1, ycf2, rpoC1, ycf3, petD and rpl16 genes in the chloroplast genome compared with those of the same genus can be used as loci for identification of the genus. In the phylogenetic results, A. crispa var. amplifolia and A. crispa var. dielsii were clustered together with 100% support, indicating that they are closely related. In this research, we analyzed the chloroplast genome structure and phylogenetic relationships of A. crispa var. amplifolia and A. crispa var. dielsii, providing an important theoretical basis for their molecular identification, genetic variation, breeding and phylogenetic analysis.

Novel discovery of schisandrin A regulating the interplay of autophagy and apoptosis in oligoasthenospermia by targeting SCF/c-kit and TRPV1 via biosensors

Oligoasthenospermia is the primary cause of infertility. However, there are still enormous challenges in the screening of critical candidates and targets of oligoasthenospermia owing to its complex mechanism. In this study, stem cell factor (SCF), c-kit, and transient receptor potential vanilloid 1 (TRPV1) biosensors were successfully established and applied to studying apoptosis and autophagy mechanisms. Interestingly, the detection limit reached 2.787 × 10-15 g/L, and the quantitative limit reached 1.0 × 10-13 g/L. Furthermore, biosensors were used to investigate the interplay between autophagy and apoptosis. Schisandrin A is an excellent candidate to form a system with c-kit similar to SCF/c-kit with a detection constant (KD) of 5.701 × 10-11 mol/L, whereas it had no affinity for SCF. In addition, it also inhibited autophagy in oligoasthenospermia through antagonizing TRPV1 with a KD of up to 4.181 × 10-10 mol/L. In addition, in vivo and in vitro experiments were highly consistent with the biosensor. In summary, high-potency schisandrin A and two potential targets were identified, through which schisandrin A could reverse the apoptosis caused by excessive autophagy during oligoasthenospermia. Our study provides promising insights into the discovery of effective compounds and potential targets via a well-established in vitro-in vivo strategy.

Comparative Study of the Two High-Efficient Strategies for in vitro Generation of Human Umbilical Cord Blood-derived Natural Killer Cells / 中国实验血液学杂志

OBJECTIVE@#To explore the similarities and variations of biological phenotype and cytotoxicity of human umbilical cord blood natural killer cells (hUC- NK) after human umbilical cord blood-derived mononuclear cells (hUC-MNC) activated and expanded by two in vitro high-efficient strategies.@*METHODS@#Umbilical cord blood mononuclear cells (MNC) from healthy donor were enriched by Ficoll-based density gradient centrifugation. Then, the phenotype, subpopulations, cell viability and cytotoxicity of NK cells derived from Miltenyi medium (denoted as M-NK) and X-VIVO 15 (denoted as X-NK) were compared using a "3IL" strategy.@*RESULTS@#After a 14-day's culture, the contents of CD3-CD56+ NK cells were elevated from 4.25%±0.04% (d 0) to 71%±0.18% (M-NK) and 75.2%±1.1% (X-NK) respectively. Compared with X-NK group, the proportion of CD3+CD4+ T cells and CD3+CD56+ NKT cells in M-NK group decreased significantly. The percentages of CD16+, NKG2D+, NKp44+, CD25+ NK cells in X-NK group was higher than those in the M-NK group, while the total number of expanded NK cells in X-NK group was half of that in M-NK group. There were no significant differences between X-NK and M-NK groups in cell proliferation and cell cycle, except for the lower percentage of Annexin V+ apoptotic cells in M-NK group. Compared with X-NK group, the proportion of CD107a+ NK cells in M-NK group were higher under the same effector-target ratio (E∶T) (P<0.05).@*CONCLUSION@#The two strategies were adequate for high-efficient generation of NK cells with high level of activation in vitro, however, there are differences in biological phenotypes and tumor cytotoxicity.

Research and exploration of salivary biological markers for hepatitis B-related hepatocellular carcinoma / 中华肝脏病杂志

Objective: To study using isotope-labeled relative and absolute quantitative proteomics methodologies to screen for salivary biological markers as a simple, non-invasive tool for identifying hepatitis B-related HCC at an early stage. Methods: Saliva samples were collected to extract salivary proteins. Isotope-labeled relative and absolute quantitative proteomics were used to analyze the differentially expressed proteins between the hepatocellular carcinoma (HCC) and non-HCC groups. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were used to verify differential proteins and identify markers in liver cancer tissues and saliva. Statistical analysis was used to analyze the diagnostic efficiency of salivary biomarkers. Results: 152 differentially expressed salivary proteins were screened out between the HCC and non-HCC groups. Western blot, immunohistochemistry, and enzyme-linked immunosorbent assays validated that the expressions of α-1-acid glycoprotein 1 (ORM1) and alpha-fetoprotein (AFP) were significantly increased in HCC (P < 0.05). There was a significant correlation between salivary AFP and serum AFP (P < 0.05). HCC was diagnosed when salivary α-1-acid glycoprotein 1 combined with AFP. The area under the receiver operating characteristic curve was 0.8726 (95% confidence interval: 0.8104 ~ 0.9347), the sensitivity was 78.3%, and the specificity was 88%. Conclusion: Salivary AFP and α-1-acid glycoprotein 1 can serve as potential biomarkers for hepatitis B-related hepatocellular carcinoma.

Survival and disease burden trend analysis of occupational pneumoconiosis from 1963 to 2020 in Shizuishan City / 中华劳动卫生职业病杂志

Objective: To understand the survival status and its influencing factors of occupational pneumoconiosis patients in Shizuishan City, and to analyze the disease burden of occupational pneumoconiosis and its trend, so as to provide scientific basis for formulating comprehensive prevention and treatment measures of occupational pneumoconiosis. Methods: A retrospective survey was conducted during July to December 2020 to explore the survival status of occupational pneumoconiosis patients who had been reported from 1963 to 2020 in Shizuishan City. The Kaplan-Meier method and Life-table method were used for survival analysis, and Cox proportional hazards regression model was used to analyze the influencing factors of survival time. The disability adjusted life years (DALY) was applied to analyze the disease burden of occupational pneumoconiosis and its temporal trend. Results: From 1963 to 2020, a total of 3263 cases of occupational pneumoconiosis were reported in Shizuishan City, of which 1467 died, so that the fatality rate was 44.96%. The median survival time was 26.71 years, average age of death was (70.55±10.92) years old. There were significant differences in the survival rates of occupational pneumoconiosis patients among different types, diagnosis age, exposure time, industry, initial diagnosis stage and whether upgraded (P<0.05) . As the survival time increased, the survival rate of patients decreased gradually. When the survival time was ≥50 years, the cumulative survival rate of patients was 4.20%. Cox regression analysis suggested that the type of pneumoconiosis, industry, diagnosis age, exposure time, initial diagnosis stage and whether upgraded were the influencing factors for the survival time of patients with occupational pneumoconiosis (P<0.05) . The total DALY attributable to occupational pneumoconiosis from 1963 to 2020 in Shizuishan City was 48026.65 person years, of which the years of life lost (YLL) was 15155.39 person years, and the average YLL was 10.33 years/person, and the years lost due to disability (YLD) was 32871.26 person years, and the average YLD was 10.07 years/person. The DALY attributed to coal worker's pneumoconiosis and silicosis were 39408.51 person years and 6565.02 person years, respectively, and they accounted for 82.06% and 13.67% of the total disease burden in Shizuishan City, respectively. The DALY caused by occupational pneumoconiosis in the age group of 40-49 years old and the first diagnosis of stage I occupational pneumoconiosis were higher, which were 20899.71 and 36231.97 person years, respectively. The average YLL and average YLD showed a volatility downtrend over time. Conclusion: The disease burden of occupational pneumoconiosis cannot be ignored in Shizuishan City, and timely targeted measures should be taken for key populations and key industries. It is recommended that life-cycle health management and hierarchical medical should be taken to improve the life quality of patients and prolong their lifes.

Silencing of Myh3 Gene by siRNA Inhibits Glycolysis in C2C12 Cells / 中国生物化学与分子生物学报

The Myh3 (myosin heavy chain 3) gene is a marker gene of muscle cell differentiation and regulates the utilization of energy in muscle cells, but whether it affects the glycolysis process of muscle cells in different states is rarely reported. In this paper, the expression patterns of Myh3 and glycolysis-related genes Pkm (M-type pyruvate kinse), Prkag3 (protein kinase adenosine monophosphate-activated γ3-subunit), and Gsk3β (glycogen synthase kinase-3β) were studied by the qRT-PCR (quantitative-Real-Time-PCR) method using C2C12 cells at different stages of myoblast and adipogenic differentiation as models. It was found that in the process of myoblast differentiation of C2C12 cells, the relative expression trends of Myh3 and glycolysis genes Prkag3 and Pkm were basically the same, and the relative expression levels first increased, reached the peak on the second day of differentiation, and then decreased; glycogen synthase the expression trend of the inhibitory gene Gsk3β was relatively stable. In the process of adipogenic differentiation of C2C12 cells, the relative expression trend of Myh3 and glycolysis genes Prkag3 and Pkm remained basically the same, and the relative expression gradually increased, reaching the highest value on the 8th day of differentiation; glycogen synthase inhibitory gene Gsk3β expression remained stable. In the myogenic differentiation state of C2C12 cells, qRT-PCR and Western blotting were used to detect the effects of interfering Myh3 on the mRNA and protein expressions of glycolysis-related genes Pkm, Prkag3, and Gsk3β. The results showed that after interfering with Myh3, the mRNA expressions of glycolysis genes Pkm and Prkag3 were significantly decreased (P 0.05). The protein levels of Myh3 and Pkm were significantly lower than those in the blank group and NC group. Under the adipogenic differentiation state of C2C12 cells, after interfering with Myh3, the mRNA levels of glycogen synthase inhibitor Gsk3β and glycolysis gene Prkag3 were significantly increased (P<0.01), and the mRNA level of glycolysis gene Pkm was decreased; the protein levels of Myh3 and Pkm in the Myh3 interference group were also lower than those in the blank group and NC group. Based on the above studies, there are significant differences in the levels of glycolysis in C2C12 cells in the myogenic and adipogenic states, and the expression patterns of Myh3 and glycolysis genes are similar. Further results showed that Myh3 suppression could inhibit the glycolysis of C2C12 cells in the myogenic state without affecting the glycogen synthesis. Unlike in the myogenic state, interfering expression of Myh3 in the adipogenic state of C2C12 cells inhibited both glycogen synthesis and glycolysis.

Effect of Buyi Pishen acupuncture on inflammatory factor and cartilage matrix in adjuvant arthritis rats / 中国针灸

OBJECTIVE@#To observe the effect of Buyi Pishen acupuncture (acupuncture for invigorating spleen and kidney) on inflammatory factor and synovial cartilage matrix in adjuvant arthritis (AA) rats, and to explore the mechanism of acupuncture for rheumatoid arthritis (RA).@*METHODS@#A total of 60 clean male Wistar rats were randomized into a normal group, a model group, a tripterygium wilfordii polyglycoside tablet (TWP) group and an acupuncture group, 15 rats in each group. Rats in the model group, the TWP group and the acupuncture group received intradermal injection of Freund's complete adjuvant (FCA) at right hind foot pad to induce the AA model. TWP suspension of 8 mg/kg was given by gavage in the TWP group. Acupuncture was applied at "Shenshu" (BL 23), "Pishu" (BL 20) and right "Housanli" (ST 36), "Sanyinjiao" (SP 6), "Yanglingquan" (GB 34) in the acupuncture group, 15 min a time, once a day. The intervention was given 15 days in both TWP group and acupuncture group. The foot-pad swelling degree before modeling, before and after intervention and the arthritis index (AI) score before and after intervention were calculated; the serum levels of interleukin (IL)-1β, IL-4, IL-10 and tumor necrosis factor-α (TNF-α) were detected by ELISA method; the ultrastructure and histomorphological changes of synovium issue were observed by transmission electron microscope and HE staining; the positive expression of matrix metalloproteinase (MMP)-3 and MMP-9 in synovium issue was detected by immunohistochemistry method.@*RESULTS@#Before intervention, foot-pad swelling degree of the model group, the TWP group and the acupuncture group was increased compared with the normal group (P<0.01). After intervention, foot-pad swelling degree and AI score were increased compared with the normal group (P<0.01), foot-pad swelling degree and AI scores in the TWP group and the acupuncture group were lower than the model group (P<0.05), and those in the acupuncture group were decreased compared with the TWP group (P<0.05). The model group exhibited unclear nuclear membrane of synovial cells, chromatin pyknosis, massive inflammatory cell infiltration and hyperplasia in synovial tissue; the TWP group and the acupuncture group exhibited clear and smooth nuclear membrane of synovial cells, inapparent chromatin pyknosis, less inflammatory cell infiltration and hyperplasia in synovial tissue, the acupuncture group exhibited less matrix destruction as well. Compared with the normal group, serum levels of IL-1β and TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were increased (P<0.01), while serum levels of IL-4 and IL-10 were decreased (P<0.01) in the model group. Compared with the model group, serum levels of IL-1β and TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were decreased (P<0.05, P<0.01), while serum levels of IL-4 and IL-10 were increased (P<0.05) in the TWP group and the acupuncture group; compared with the TWP group, serum level of TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were decreased (P<0.05), while serum levels of IL-4 and IL-10 were increased (P<0.05) in the acupuncture group.@*CONCLUSION@#Buyi Pishen acupuncture can effectively improve the injury of articular cartilage in AA rats, its mechanism maybe related to reducing the inflammatory reaction in synovium and inhibiting the degradation of articular cartilage matrix.

Anti-tumor mechanism of sesquiterpenoids from Cryptoporus volvatus based on molecular docking / 南方医科大学学报

OBJECTIVE@#To identify the target genes mediating anti-tumor effect of sesquiterpenoids from Cryptoporus volvatus and explore the possible mechanism using molecular docking and molecular dynamics simulation.@*METHODS@#Based on the chemical structure of sesquiterpenes from C. volvatus, we explored the online reverse target finding websites PharmMapper, SEA, Target Hunter and related literature for preliminary prediction of possible anti-tumor targets. Discovery Studio 4.0 (Libdock function) and Maestro 12.3 were used to connect sesquiterpenes with the possible targets, and the potential targets were selected according to the scores. The interaction between the sesquiterpenes and the targets were analyzed using 2D interaction diagram, and the influence of different sesquiterpene skeletons on their activity was inferred based on their activity measurements in experiment. Kinetic simulation was performed for front-end protein sequence (1UNQ) of the Akt (protein kinase B) and for the complex formed by 1UNQ and compound 4 (which had the best cytotoxic activity in vitro) in its optimal conformation, and the root mean square deviation (RMSD) value and root mean square float (RMSF) value of the complex and 1UNQ were measured to evaluate the stability of the binding of compound 4 to the target.@*RESULTS@#The sesquiterpenes showed optimal binding with 1UNQ. Analysis of 2D interaction diagram suggested that the hydrogen bonding and electrostatic force were the most important forces mediating the interaction between the sesquiterpenes and 1UNQ. Analysis of the optimal 3D conformation showed that for different sesquiterpenes, a slight change of the molecular framework produced a steric hindrance effect and caused changes in their bioactivity. Kinetic simulation showed that the complex formed by compound 4 and1UNQ had a lower RMSD than the target pure protein sequence, indicating that compound 4 could stably bind to 1UNQ. The anti-tumor effect of the sesquiterpenoids from C. volvatus was associated with their ability to cause Lys-144 acetylation, which blocks Akt binding to the downstream PIP3 and thus affects the proliferation of tumor cells.@*CONCLUSION@#1UNQ is the target of sesquiterpenoids from C. volvatus, which affects the proliferation of tumor cells by acetylating Lys-14.

Analysis on YABBY Transcription Factor Family of Original Plant Cannabis sativa of Traditional Chinese Medicine Cannabis Fructus / 中国实验方剂学杂志

Objective:To analyze the sequence characteristics，chromosomal location，gene structure，conserved motifs，phylogenetic evolution and differential gene expressions of the <italic>Cannabis sativa</italic> YABBY transcription factor family，in order to provide a molecular basis for in-depth study of <italic>YABBY</italic> gene function and theoretical support for the selection and breeding of superior hemp varieties. Method:The bio-informatics method was used to identify and analyze the <italic>CsYABBY </italic>gene family of the original hemp seed plant. PlantTFDB，ExPASy，MEME，CELLO，PLANTCARE and other online websites and TBtools，MEGA，DNAMAN and other software were used for prediction，visualization and analysis. Result:<italic>C. sativa</italic> contains 6 <italic>YABBY</italic> gene members distributed on 5 chromosomes，in which 5 members are localized in the nucleus and 1 in extracellular， they consist of 185-235 amino acids， and the isoelectric point is between 5.05 and 9.34， the molecular weight is between 20 582.45-26 282.7 Da. All of CsYABBY proteins contain two conserved domains， namely Zinc finger domain and YABBY domain. <italic>CsYABBY</italic> genes have multiple cis-acting elements，and their expressions differ in different tissues and cultivars. Conclusion:The expressions of CsYABBY may be affected by hormones and externally environmental factors. <italic>CsYABBY</italic> gene expressions are tissue-specific. In addition，YABBY transcription factor family may play an important role in regulating the development of <italic>C. sativa</italic> female flowers，and subfamilies YAB1 and YAB5 may be involved in the synthesis of cannabinoids.

Progress of Aflibercept of clinical application for neovascular age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

@#Aflibercept is a recombinant human fusion protein that acts as a soluble decoy receptor for vascular endothelial growth factor(VEGF)family members. VEGF-A, VEGF-B and placental growth factor(PLGF)were included in VEGF family that could inhibit downstream signalling mediated by these ligands. Aflibercept binds to all isoforms of VEGF-A with high affinity, and presented a markedly higher affinity compared with ranibizumab or bevacizumab. Intravitreal injection aflibercept has been approved for the treatment of patients with age-related macular degeneration(ARMD). Numerous studies showed it could improve best corrected visual acuity(BCVA), reduce macular edema and with fewer complications that has been another choice for ARMD patients. However, studies of participation time with large sample are lacking, and relevant studies are limited in China. Contribution in clinical efficacy, advancement in selection and use of medicines, safety and limitations with aflibercept will be here summarized.

Sepsis risk calculator-guided antibiotic management in neonates with suspected early-onset sepsis / 中国当代儿科杂志

OBJECTIVE@#To evaluate the efficacy of sepsis risk calculator (SRC) in guiding antibiotic use in neonates with suspected early-onset sepsis (EOS).@*METHODS@#A total of 284 neonates with a gestational age of ≥ 35 weeks were enrolled as the control group, who were hospitalized in the Children's Hospital of Chongqing Medical University from March to July, 2019 and were suspected of EOS. Their clinical data were retrospectively collected and the use of antibiotics was analyzed based on SRC. A total of 170 neonates with a gestational age of ≥ 35 weeks were enrolled as the study group, who were admitted to the hospital from July to November, 2020 and were suspected of EOS. SRC was used prospectively for risk scoring to assist the decision making of clinical antibiotic management. The two groups were compared in terms of the rate of use of antibiotics, blood culture test rate, clinical outcome, and adherence to the use of SRC.@*RESULTS@#Compared with the control group, the study group had a significantly higher SRC score at birth and on admission (@*CONCLUSIONS@#The use of SRC reduces the rate of empirical use of antibiotics in neonates with suspected EOS and does not increase the risk of adverse outcomes, and therefore, it holds promise for clinical application.

Research progress of effect of anxiolytic traditional Chinese medicines and formulas on neurotransmitters / 中国中药杂志

Anxiety disorders are a common mental illness that seriously endangered physical and mental health of human beings. The etiology of anxiety disorders is closely related to the abnormality of monoamines neurotransmitters, amino acids neurotransmitters and neuropeptides. The long-term use of anti-anxiety chemical drugs has some adverse effects, such as constipation, muscle relaxation, lethargy, tolerance and withdrawal symptoms. However, traditional Chinese medicines have advantages of multi-component, multi-target coordination, with less adverse reactions. Therefore, it is a promising prospect to develop novel anti-anxiety drugs from traditional Chinese medicines and formulas. This article reviewed some traditional Chinese medicines and formulas that can relieve anxiety symptoms. These include traditional Chinese medicines(Panax ginseng, Lycium ruthenium, Morus alba, Bupleurum plus dragon bone oyster soup, Chailong Jieyu Pills, and Naogongtai Formulas) with the effect on monoamine neurotransmitters, such as serotonin, dopamine, and norepinephrine; traditional Chinese medicines(Rehmannia glutinosa, Ziziphus jujuba Mill. var. spinosa, Jielv Anshen Decoction, Baixiangdan Capsules, Antianxietic Compound Prescription Capsules) with the effect on amino acid neurotransmitters, such as glutamic acid, γ-aminobutyrc acid; and traditional Chinese medicines(P. ginseng, Xiaoyao San, Shuyu Ningxin Decoction)with the effect on neuropeptide Y pathway, with the aim to provide theoretical basis for the further development of some novel and more effective anti-anxiety therapeutics from traditional Chinese medicine and formulas.

Microecology and geoherbalism of traditional Chinese medicine / 中国中药杂志

Microecology was directly or indirectly involved in the growth and development, metabolism process, and component accumulation of traditional Chinese medicine(TCM) in various ways, which affected the formation and changes of the geoherbalism of TCM. It was one of the main tasks of traditional Chinese medical microecology(TCMM) to reveal the relationship among microecological structure and its change rule and the quality effect of TCM. The heterogeneity of soil environment caused by geographical and climatic factors, as well as the discreteness limitation caused by isolation factors such as distance and host selection, were the main causes of the differentiation of microecological geography of TCM. The microecology of TCM had important influences and contributions on the distinctive origin and quality of Dao-di herbs, which was mainly reflected in the formation of excellent germplasm(including disease and insect resistance, drought resistance, salt resistance, cold resistance, etc.), the increase of yield, the formation of medicinal parts, the metabolism and accumulation of effective components, the time limit of harvesting, and the toxicity, increasing efficiency or reducing toxicity of TCM in the processing, the changes of product efficiency after introduction, and the authenticity of fungus medicine. With the vigorous development of metabonomics and modern information technology, the following aspects would become the future research trends, including the microecologically mediated biogenic pathway of chemical components, the metabolic synthesis reactor of TCM based on the microecological quantitative effect relationship, the cultivation of genuine Chinese medicine based on reconstruction of microecological structure, the origin identification barcode traceability technology, and the toxicity reduction and efficiency enhancement technology of TCM based on the microecological.

C-reactive protein-guided antibiotic treatment strategy for neonates with suspected early-onset sepsis / 中国当代儿科杂志

OBJECTIVE@#To evaluate the efficacy and safety of C-reactive protein (CRP)-guided antibiotic treatment strategy for neonates with suspected early-onset sepsis (EOS).@*METHODS@#A total of 428 neonates, with a gestational age of >35 weeks, who were admitted to the Children's Hospital of Chongqing Medical University from February to July, 2019 and were suspected of EOS were enrolled as the observation group. The effect of antibiotic treatment was prospectively observed, and if clinical symptoms were improved and CRP was 35 weeks) who were admitted to this hospital from February to July, 2018 and were suspected of EOS were enrolled as the control group, and the use of antibiotics was analyzed retrospectively. The two groups were compared in terms of duration of antibiotic treatment, length of hospital stay, incidence rate of repeated infection and clinical outcome.@*RESULTS@#Compared with the control group, the observation group had significantly shorter duration of antibiotic treatment and length of hospital stay (P0.05).@*CONCLUSIONS@#For neonates with a gestational age of >35 weeks and a suspected diagnosis of EOS, CRP-guided antibiotic treatment strategy can shorten duration of antibiotic treatment and length of hospital stay and does not increase the incidence rate of repeated infection. Therefore, it holds promise for clinical application.

Research on Natural Boundary of Traditional Geo-authentic Origin of Ligusticum chuanxiong via Soil Elements Characteristics Along Same Longitude / 中国实验方剂学杂志

Objective:To find the natural environmental boundary of the origin of the authentic Ligusticum chuanxiong by analyzing the distribution characteristics of soil elements in the traditional geo-authentic area and the southern continuous expanding areas along the same longitude. Method:The contents of 24 elements both in soil and plant L. chuanxiong samples were determined by using X-ray fluorescence spectrometry （XRF） and ICP-MS，etc. Spearman correlation test was used to evaluate the correlations of rhizosphere soil and each portion of L. chuanxiong，to screen out “characteristic elements”. Bray-Curtis similarity indexes based on all elements and "characteristic elements" were used for hierarchical cluster analysis of soil samples, to identify the sample range with similar soil element charateristics to the traditional geo-authentic area of L. chuanxiong. Result:K，Mg，Mn and Rb elements were significantly correlated in rhizosphere soil and plant L. chuanxiong. Geographical differentiation of all elements and four characteristic elements showed that there was a highest similarity between geo-authentic area and its neighbor plots S1-S6 (except plot S4) in soil elements distribution, followed by plots S14-S16. The middle section plots S7-S13 in the expansion areas were quite different from the traditional geo-authentic production areas. Conclusion:The soil element characteristics in the study areas were not completely controlled by geographical distance，but demonstrated the "fault" variation in the areas along longitude. This study provides a theoretical basis for the detrrmination of suitable cultivation area for Ligusticum Chuanxiong, and the natural boundary of its geo-authentic area may be extended an additional 60 km southward along longitude beyond the traditional origin. Additionally， K，Mg，Mn and Rb characteristic elements may be the potential markers to evaluate the suitable soil environment for cultivating L. chuanxiong.

Prevalence of Disaccharidase Deficiency in Adults With Unexplained Gastrointestinal Symptoms

Background/Aims@#Disaccharidase assay is used for assessing carbohydrate intolerance in children, but its usefulness in adults is not known. The aim of this study is to assess the prevalence of disaccharidase deficiency in patients with unexplained gastrointestinal symptoms. @*Methods@#A retrospective review of adults with chronic (> 1 year) abdominal symptoms and negative imaging and endoscopy/colonoscopy and who completed bowel symptom questionnaire and duodenal biopsy for lactase, maltase, sucrase, and palatinase was performed. A subset also underwent 25 g lactose breath test (LBT). @*Results@#One hundred twenty patients (females = 83) were evaluated, of whom 48 also underwent LBT. Fifty-six (46.7%) patients had enzyme deficiency; 44 (36.7%) had single (either lactase or maltase), 1 had 3 enzyme deficiencies, 11 (9.2 %) had all 4 disaccharidase enzyme (pan-disaccharidase) deficiency, and 64 (53.0%) had normal enzyme levels. Baseline prevalence and severity of 11 gastrointestinal symptoms were similar between normal and single enzyme deficiency groups. The sensitivity and specificity of LBT was 78.3% and 72.0%, respectively and overall agreement with lactase deficiency was 75.0%. @*Conclusions@#Isolated disaccharidase deficiency occurs in adults, usually lactase and rarely maltase, and pan-disaccharidase deficiency is rare. Baseline symptoms or its severity did not predict enzyme deficiency.

Transmission electron microscopic observation on gonad of Oncomelania hupensis offspring bred in Weishan Lake areas / 中国血吸虫病防治杂志

Objective To observe the morphological changes in the testes and ovaries of adult 12th-generation Oncomelania hupensis bred for 12 winters in Weishan Lake areas. Methods The offspring of the adult O. hupensis snails bred in the Weishan Lake that were originated from the Yangzhou section of the Yangtze River was defined as the experiment group, while uninfected, adult O. hupensis snails captured from the marshland of the Yangzhou section of the Yangtze River served as the control group. Snails were dissected and intact testicular and ovarian specimens were sampled, routinely fixed, dehydrated, embedded, polymerized in an oven and sliced on an ultramicrotome. The sections were visualized under a transmission electron microscope, and the ultrastructure of the snail gonad was compared between the experiment and control groups. Results Transmission electron microscopy showed “9 + 2” microtubules on the transverse sections of the tails of sperm cells in the testes of male snails in the control group, with triangular acrosomes and spiral, dense nuclei seen in the tip, while in the experiment group, the “9 + 2” microtubules disappeared on the transverse sections of the tails of sperm cells in the testes of male snails, with low chromatin density found in the tip. Transmission electron microscopy revealed clear nucleolus and nuclear membranes in the ova of female snail ovaries, and displayed yolk body, liposomes and endoplasmic reticulum in the cytoplasm, bilayer twists of nuclear membrane and a uniform nucleolus in the control group, while in the experiment group, smooth nuclear membrane and unclear nucleolus were observed in the ova of female snail ovaries, with few contents seen within cells. Conclusions Following breeding for 12 winters in the Weishan Lake, the 12th-generation O. hupensis snails fail to fully adapt to the natural environment in northern China, and the remarkable changes in the ultrastructure of the snail gonad may be a cause of gradual decline and even extinction of O. hupensis in the Weishan Lake areas.

Measurement of commonly-used echocardiography indexes and determination of reference values in pregnant women with normal pregnancy / 中国实用妇科与产科杂志

OBJECTIVE: To compare the echocardiography parameters during different pregnancy trimesters and to determine the reference range of echocardiography for pregnant women.METHODS: Normal pregnant women were recruited from Renji Hospital,Shanghai Jiao Tong University School of Medicine from February 2017 to December 2017.Women were randomly assigned into 4 groups,cardiac ultrasonography was performed in any one of the three trimesters or 42 days postpartum,and the reference ranges of indicators were determined in each group.Non-pregnant women of childbearing age were recruited as controls.Make a comparison of the measurement values of echocardiography at different trimesters of pregnancy.RESULTS: A total of 733 normal pregnant and non-pregnant women were enrolled,and reference values of echocardiography indexes were determined.The reference range of echocardiograph parameters for pregnant women was established for the first time.Compared with non-pregnant women,there were significant differences in echocardiography parameters among these groups. With the increase of gestational age,the radial lines of left and right atria and ventricles enlarged;the aortic root diameter and pulmonary artery diameter increased,and left and right heart systolic function declined. Most of the above changes reached a peak in the third trimester and did not return to the nonpregnancy level at 42 days postpartum. The diastolic function did not change significantly throughout pregnancy or 42 days postpartum.CONCLUSION: The current normal reference range of echocardiography is not fully applicable to pregnant women,so it is of great importance to establish a normal reference range of echocardiography for pregnant women.