Infectious diseases continue to pose a threat to global public health. Successive global shocks caused by emerging and re-emerging pathogens have continuously challenged existing surveillance systems, highlighting the urgent need to build efficient and precise pathogen surveillance networks. Pathogen genomic databases have been developed rapidly in recent two decades, significantly improving the molecular identification, evolutionary analysis, and transmission tracking of pathogens, and changing disease surveillance strategies and patterns. This paper summarizes the developmental history and current state of pathogen genomic databases, and discusses their applications in public health, including pathogen variation surveillance, emerging or suspected pathogen identification, and epidemiological tracing. Furthermore, this paper systematically analyzes the limitations and key challenges faced by current global health prevention and control system, and suggests the focus of the development of online pathogen databases to address existing shortcomings, ultimately improve global infectious disease surveillance and early warning

Infectious diseases continue to pose a threat to global public health. Successive global shocks caused by emerging and re-emerging pathogens have continuously challenged existing surveillance systems, highlighting the urgent need to build efficient and precise pathogen surveillance networks. Pathogen genomic databases have been developed rapidly in recent two decades, significantly improving the molecular identification, evolutionary analysis, and transmission tracking of pathogens, and changing disease surveillance strategies and patterns. This paper summarizes the developmental history and current state of pathogen genomic databases, and discusses their applications in public health, including pathogen variation surveillance, emerging or suspected pathogen identification, and epidemiological tracing. Furthermore, this paper systematically analyzes the limitations and key challenges faced by current global health prevention and control system, and suggests the focus of the development of online pathogen databases to address existing shortcomings, ultimately improve global infectious disease surveillance and early warning

Objective To establish an allogeneic rat model of endometriosis and to evaluate the effects of gonadotropin-releasing hormone (GnRH) agonist GenSci006 on experimental rat endometriosis. Methods Endometrium from SPF grade donor female SD rats were transplanted onto the abdominal wall of recipient female rats to construct an allogeneic endometriosis model. The rats undergoing sham surgery were divided into the sham group. Three weeks later, the length, width and height of the ectopic endometrium were measured, and the volume of the endometrium (V₁) was calculated before drug administration. The modeling rats were randomly divided into four groups: model group, triptorelin group (0.25 mg/kg), GenSci006-1 group (0.125 mg/kg) and GenSci006-2 group (0.25 mg/kg). Each group had 16 rats and received a single dose of the corresponding drug. The sham group and model group were administered an equal volume of solvent. Three weeks after administration, ectopic endometrium was measured to calculate the volume V₂ and inhibition rate. The effect of GenSci006 on rat uterus and ovarian tissues was assessed by comparing organ coefficients and changes in pathological sections. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of serum estradiol (E₂), progesterone (P₄), follicle stimulating hormone (FSH), and luteinizing hormone (LH). Real-time fluorescent quantitative PCR was used to detect the expression of GnRH receptor (GnRHR) mRNA in the hypothalamus and pituitary. Western blot was used to detect the expression of estradiol receptor alpha (ERα), beta (ERβ) and progesterone receptor (PR) in ectopic endometrium. Results Three weeks after administration, compared with the model group, the body weight of rats in the triptorelin and GenSci006-2 groups significantly increased (P < 0.05), while the volume of ectopic endometrium significantly decreased (P < 0.05). Compared with the sham group, the model group showed no significant changes in uterine and ovarian organ coefficients or endometrial thickness (P > 0.05). Compared with the model group, the uterine organ coefficients and endometrial thickness were significantly reduced in the triptorelin and GenSci006-2 groups (P < 0.05). Compared with the sham group, the serum levels of E₂, P₄, FSH and LH in the model group showed no significant changes (P > 0.05). Compared with the model group, the ovarian organ coefficient and serum P₄ levels of rats in the Triptorelin, GenSci006-1, and GenSci006-2 groups were significantly reduced (P < 0.05), while the serum LH levels of rats in the GenSci006-1 group were significantly increased (P < 0.05). However, there were no significant changes in serum E₂ and FSH levels in each group (P > 0.05). Compared with the model group, the expression levels of GnRHR mRNA in the pituitary tissue of rats in the triptorelin and GenSci006-2 groups were significantly downregulated (P < 0.05), with no significantly changes in the hypothalamus (P > 0.05). There were no significant changes in the expression level of GnRHR mRNA in the hypothalamus or the protein levels of ERα, ERβ and PR in the ectopic endometrial tissue in any group (P > 0.05). Conclusion The allogeneic endometriosis rat model is a suitable animal model for screening and evaluating drugs for treating endometriosis. The volume of ectopic endometrium, inhibition rate, uterine and ovarian organ coefficients, and serum E₂ levels may serve as indicators for detecting drug efficacy.

Objective:To explore the effects of consecutively repeated application of emergency contraception pills (ECPs) containing levonorgestrel (LNG) on the female fertility and the health outcomes of F1 generation rats.Methods:Female SPF rats were intragastric administered with LNG-ECPs consecutively for 3 (P-3), 6 (P-6) and 12 (P-12) estrous cycles (three times in each estrous cycle), respectively. Under each administration schedule, rats were randomly divided into 2 groups according to body weight stratification using random numbers generated in Excel, i.e. LNG-ECPs group and solvent control group, administered with 0.12 mg/kg LNG-ECPs and corresponding volumes of 0.5% CMC-Na, respectively. Four hours after the last dosing, half of the animals (12-18) in each group were allotted randomly for dissection (6-9) and mating (6-9), respectively. The remaining half (12-18) were recovered for 3 estrous cycles, and then were randomly allocated for dissection (6-9) and mating (6-9). Organ coefficients were calculated. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, testosterone, anti-Müllerian hormone (AMH) and free thyroid hormone 3 (fT3) were examined by enzyme linked immunosorbent assay (ELISA). Ovarian tissues were sectioned and stained with hematoxylin and eosin (HE) for follicle counting. In addition, the pregnancy rate and litter size of the female rats were recorded, and the growth indexes and behavioral parameters of the cubs were measured. Moreover, RNA sequencing (RNA-seq) of the ovarian tissues was performed to establish the differential expression gene profile of ovarian injury induced by LNG-ECPs. Then gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed.Results:1) After consecutive administration for 3 and 6 estrous cycles, LNG-ECPs showed no significant impact on the serum hormone levels and female fertility (all P>0.05), and the growth indexes and behavioral parameters of the F1 generation (all P>0.05). 2) After consecutive administration for 12 estrous cycles, the serum levels of FSH [(0.21±0.17) U/L], LH [(0.27±0.08) U/L] and progesterone [(0.68±0.23) μg/L] in LNG-ECPs group decreased significantly compared with those in solvent control group [(1.00±0.82) U/L, P=0.043; (1.00±0.50) U/L, P=0.006; (1.00±0.20) μg/L, P=0.027], while the level of estradiol [(2.24±1.03) μg/L] and testosterone [(1.25±0.25) μg/L] increased noticeably compared with those in solvent control group [(1.00±0.35) μg/L, P=0.019; (1.00±0.07) μg/L, P=0.044]. The number of primordial follicles (4.88±2.36) lost distinctly, while the number of atretic follicles (24.38±5.01) increased markedly in LNG-ECPs group compared with those in solvent control group (16.13±9.36, P=0.005; 19.13±2.30, P=0.018). In addition, the weight-loaded swimming (WLS) time of the F1 generation rats from the LNG-ECPs group [(157.13±32.29) s] reduced obviously compared with those from the solvent control group [(198.06±40.01) s, P=0.003]. Moreover, after recovering for 3 estrous cycles, LNG-ECPs significantly increased the levels of FSH [(2.48±1.18) U/L], LH [(1.60±0.41) U/L], testosterone [(1.37±0.23) μg/L] and the ratio of FSH/LH (1.61±0.41) compared with those in solvent control group [(1.00±0.67) U/L, P=0.024; (1.00±0.27) U/L, P=0.014; (1.00±0.18) μg/L, P=0.011; 1.00±0.49, P=0.042], respectively. Additionally, the serum levels of estradiol [(0.49±0.15) μg/L] and AMH [(0.79±0.15) μg/L] were significantly lower than those in solvent control group [(1.00±0.37) μg/L, P=0.011; (1.00±0.10) μg/L, P=0.016]. In addition, the number of primordial follicles in rats of LNG-ECPs group (6.25±5.06) were obviously less than that in solvent control group (12.00±5.56, P=0.048). Furthermore, the total distance in open field [(89.85±36.98) m] and the swimming time in WLS [(112.00±29.52) s] in rats treated with LNG-ECPs both decreased distinctly compared with those in solvent control group [(147.55±23.13) m, P<0.001; (137.69±25.85) s, P=0.014]. 3) According to transcriptomic analysis, Cd5, Cxcr1, Lexm, Fga, Mybphl and Gstm5 were the significant differential expressed genes (DEGs) in the ovarian tissues of rats. These DEGs were involved in pathways related to steroid hormone biosynthesis, including terpenoid backbone biosynthesis, ovarian steroidogenesis, cortisol synthesis and secretion. Additionally, these genes were involved in metabolic processes, such as carbon metabolism, butanoate metabolism, cysteine and methionine metabolism. And the genes were also involved in immunoregulatory processes including cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptors. Conclusion:Consecutively repeated administering LNG-ECPs to the female rats in a short-term period (<12 cycles) did not demonstrate significant adverse effects on female fertility and the growth and development and the behaviors of their F1 generation cubs. However, long-term repeated treatment with LNG-ECPs (12 cycles) caused ovarian injury on female rats and showed negative impacts on the health of the F1 generation cubs, and no significant improvement was observed after recovering for 3 estrous cycles.

Objective:To explore the effects of consecutively repeated application of emergency contraception pills (ECPs) containing levonorgestrel (LNG) on the female fertility and the health outcomes of F1 generation rats.Methods:Female SPF rats were intragastric administered with LNG-ECPs consecutively for 3 (P-3), 6 (P-6) and 12 (P-12) estrous cycles (three times in each estrous cycle), respectively. Under each administration schedule, rats were randomly divided into 2 groups according to body weight stratification using random numbers generated in Excel, i.e. LNG-ECPs group and solvent control group, administered with 0.12 mg/kg LNG-ECPs and corresponding volumes of 0.5% CMC-Na, respectively. Four hours after the last dosing, half of the animals (12-18) in each group were allotted randomly for dissection (6-9) and mating (6-9), respectively. The remaining half (12-18) were recovered for 3 estrous cycles, and then were randomly allocated for dissection (6-9) and mating (6-9). Organ coefficients were calculated. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, testosterone, anti-Müllerian hormone (AMH) and free thyroid hormone 3 (fT3) were examined by enzyme linked immunosorbent assay (ELISA). Ovarian tissues were sectioned and stained with hematoxylin and eosin (HE) for follicle counting. In addition, the pregnancy rate and litter size of the female rats were recorded, and the growth indexes and behavioral parameters of the cubs were measured. Moreover, RNA sequencing (RNA-seq) of the ovarian tissues was performed to establish the differential expression gene profile of ovarian injury induced by LNG-ECPs. Then gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed.Results:1) After consecutive administration for 3 and 6 estrous cycles, LNG-ECPs showed no significant impact on the serum hormone levels and female fertility (all P>0.05), and the growth indexes and behavioral parameters of the F1 generation (all P>0.05). 2) After consecutive administration for 12 estrous cycles, the serum levels of FSH [(0.21±0.17) U/L], LH [(0.27±0.08) U/L] and progesterone [(0.68±0.23) μg/L] in LNG-ECPs group decreased significantly compared with those in solvent control group [(1.00±0.82) U/L, P=0.043; (1.00±0.50) U/L, P=0.006; (1.00±0.20) μg/L, P=0.027], while the level of estradiol [(2.24±1.03) μg/L] and testosterone [(1.25±0.25) μg/L] increased noticeably compared with those in solvent control group [(1.00±0.35) μg/L, P=0.019; (1.00±0.07) μg/L, P=0.044]. The number of primordial follicles (4.88±2.36) lost distinctly, while the number of atretic follicles (24.38±5.01) increased markedly in LNG-ECPs group compared with those in solvent control group (16.13±9.36, P=0.005; 19.13±2.30, P=0.018). In addition, the weight-loaded swimming (WLS) time of the F1 generation rats from the LNG-ECPs group [(157.13±32.29) s] reduced obviously compared with those from the solvent control group [(198.06±40.01) s, P=0.003]. Moreover, after recovering for 3 estrous cycles, LNG-ECPs significantly increased the levels of FSH [(2.48±1.18) U/L], LH [(1.60±0.41) U/L], testosterone [(1.37±0.23) μg/L] and the ratio of FSH/LH (1.61±0.41) compared with those in solvent control group [(1.00±0.67) U/L, P=0.024; (1.00±0.27) U/L, P=0.014; (1.00±0.18) μg/L, P=0.011; 1.00±0.49, P=0.042], respectively. Additionally, the serum levels of estradiol [(0.49±0.15) μg/L] and AMH [(0.79±0.15) μg/L] were significantly lower than those in solvent control group [(1.00±0.37) μg/L, P=0.011; (1.00±0.10) μg/L, P=0.016]. In addition, the number of primordial follicles in rats of LNG-ECPs group (6.25±5.06) were obviously less than that in solvent control group (12.00±5.56, P=0.048). Furthermore, the total distance in open field [(89.85±36.98) m] and the swimming time in WLS [(112.00±29.52) s] in rats treated with LNG-ECPs both decreased distinctly compared with those in solvent control group [(147.55±23.13) m, P<0.001; (137.69±25.85) s, P=0.014]. 3) According to transcriptomic analysis, Cd5, Cxcr1, Lexm, Fga, Mybphl and Gstm5 were the significant differential expressed genes (DEGs) in the ovarian tissues of rats. These DEGs were involved in pathways related to steroid hormone biosynthesis, including terpenoid backbone biosynthesis, ovarian steroidogenesis, cortisol synthesis and secretion. Additionally, these genes were involved in metabolic processes, such as carbon metabolism, butanoate metabolism, cysteine and methionine metabolism. And the genes were also involved in immunoregulatory processes including cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptors. Conclusion:Consecutively repeated administering LNG-ECPs to the female rats in a short-term period (<12 cycles) did not demonstrate significant adverse effects on female fertility and the growth and development and the behaviors of their F1 generation cubs. However, long-term repeated treatment with LNG-ECPs (12 cycles) caused ovarian injury on female rats and showed negative impacts on the health of the F1 generation cubs, and no significant improvement was observed after recovering for 3 estrous cycles.

Aim To study the function of VR1 in chronic pain, to construct VR1 siRNA expression vectors and to study their silencing effect in the DRG neurons of rats were detected.Methods The hairpin sequences of siRNAs targeting VR1 gene of rat were designed, and two pairs of oligonucleotide sequence were synthesized. The annealed oligonucleotide fragments were cloned into linearized pRNAT-U6.2/Lenti expression vector and identified by PCR and DNA sequencing.Then, they were co-transfected by lipofectamine into 293T cells.The silencing effects of the lentivector-mediated VR1 siRNAs on the expression of VR1 mRNA were determined by RT-PCR after intrathecal injection in rats.Results DNA sequencing showed that the oligonucleotide fragments were correctly cloned into linearized pRNAT-U6.2/Lenti expression vector and the expression of VR1 mRNA in L4-L6 DRG neurons was inhibited significantly by pRNAT-U6.2/Lenti-siVR1 after intrathecal injection in rats.Conclusion The lentivector-mediated siRNAs are successfully constructed and they inhibit the expression of VR1 mRNA in the DRG neurons of rats, which may provide a potential tool for the further study and treatment of chronic pain.

Aim To investigate the angiogenic promoting effect of Morinda officinalis How oligosaccharides(MOO) in the ischemic myocardium of rats after acute myocardial infarction(AMI).Methods 40 male Wistar rats were established into AMI model successfully and were randomly divided into 5 groups equally, i. e. the low, medium and high doses of MOO groups, the Shexiangbaoxin group and the model group. They were treated with different doses of the water fraction of the ethanolic extract of Radix morinda officinalis (0.7, 1.4, 2.8 mg·kg~(-1) ·d~(-1)), suspension liquid of Shexiangbaoxin Pill(30 mg·kg~(-1) ·d~(-1)) and distilled water with the same volume respectively.Besides, a sham operated group with 10 rats was set up for control. All rats were sacrificed after 6-week-treatment.The Ⅷ coagulation factor, vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(bFGF) protein in ischemic myocardium of rats in each group were detected by immunohistochemistry assay.The microvessel density(MVD) was calculated. Gray values of protein expression of VEGF and bFGF in ischemic myocardium were calculated and analyzed by image analysis system.Results The MVD, the gray values of VGF and bFGF were higher in the medium and high doses of MOO groups than those in the model group(P <0.05), but still lower than those in the Shexiangbaoxin group(P <0.05). The MVD and the gray values of VEGF among 3 doses of MOO groups showed significant differences (P <0.05).Significant differences of gray value of bFGF were observed between small and middle doses of MOO groups, also between small and large doses of groups(P <0.05).Conclusion MOO can obviously promote angiogenesis in the ischemic myocardium of the rats after AMI.And up-regulating expressions of VEGF and bFGF protein in the ischemic myocardium may act as one of its angiogenic promoting mechanisms.

Aim To study the effects of amitriptyline(Ami)on focal cerebral ischemia-reperfusion injury in rats.Methods An animal model of focal cerebral ischemia-reperfusion injury was induced by the middle cerebral artery occlusion(MCAO) by reversibly inserting a nylon thread method.The rats were decapitated after ischemia for 1 hour and reperfusion for 2 hours.The infarct volumes were determined using a 2,3,5-tri-phenyl tetrazolium chloride(TTC) staining and assessed by image analysis system.The neurologic deficit status were evaluated on 0~5 grade scale.The levels of dopamine(DA),norepinephrine(NE),serotonin(5-HT) and its metabolic product~hydroxyindole acetic acid(5-HIAA) in cortex and striatum were measured by fluoro-spectrophotometry.Results Ami treatment exhibited a remarkable reduction in infarct volume and neurologic deficit scores.The monoamines content of cortex and striatum had a significant increase compared with ischemia-reperfusion group.Conclusion Amitriptyline has protective effect on cerebral ischemia-reperfusion injury in rats.The mechanism might be related to reducing the release of NE,DA and 5-HT during cerebral ischemia-reperfusion,attenuating or inhibiting of the neurotoxic effects of monoamine neurotransmitters.

AIM To study the effects of matrine (Ma) on the action potential and contractile force in guinea pig papillary muscles. METHODS Conventional microelectrode technique was used to record the fast action potentials (FAP) and slow action potentials (SAP) induced by histamine and BaCl_2 of guinea pig papillary muscles. RESULTS Ma 10,25,50 ?mol?L -1 dose-dependently prolonged the action potential duration at 50%, 90% repolarization (APD_ 50 , APD_ 90 ) and effective refractory period (ERP) of FAP, and lengthened the APD_ 50 , APD_ 90 of SAP induced by histamine and BaCl_2 when perfused with KCl 25 mmol?L -1 Tyrode's solution. The maximal upstroke velocity (V_ max ) of FAP, SAP and contractile force (Fc) were not affected by matrine 10,25,50 ?mol?L -1 . CONCLUSION It was suggested that Matrine could block K + channels in the myocardium.-