Objective:To investigate the structural changes in the spinal cord in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) and their relationship with clinical disability.Methods:This study was cross-sectional. A retrospective analysis of clinical and imaging data from 124 patients with MS (MS group), 101 patients with aquaporin-4 antibody-positive NMOSD (NMOSD group), and 110 healthy controls (HC group) from seven medical centers were conducted from January 2018 to October 2021. All subjects underwent 3D T 1WI, and the upper cervical spinal cord cross-sectional area (MUCCA) was segmented and measured. All patients completed the expanded disability status scale (EDSS) assessments at baseline and during follow-up, as well as the baseline 25-foot walk test (T25FW) and the nine-hole peg test (NHPT). Patients were classified into EDSS progression and non-progression groups based on follow-up EDSS scores. Comparisons of MUCCA among the three groups were conducted using analysis of covariance, controlling for age and sex as covariates. Pairwise comparisons between groups were performed using the HSD test. Univariate linear regression and logistic models were employed to identify candidate predictors of baseline clinical disability status or EDSS progression in the MS and NMOSD groups. L1 regularized multivariable linear regression analysis was used to determine independent predictors of baseline clinical disability status or EDSS progression. Independent predictors were then combined to establish a logistic regression model, and the model′s performance in predicting EDSS progression was evaluated using receiver operating characteristic analysis and the area under the curve (AUC). Results:A total of 144 patients completed follow-up EDSS assessments, with a follow-up duration of 3.30 (1.10, 6.42) years, including 82 patients in the MS group and 62 patients in the NMOSD group. Controlling for sex and age as covariates, the overall difference in MUCCA among the MS, NMOSD, and HC groups was statistically significant ( P=0.001). The MUCCA in the MS group was lower than that in the HC group, with a significant difference ( t=-2.54, P=0.007); the MUCCA in the NMOSD group was also lower than that in the HC group, with a significant difference ( t=-2.80, P=0.002). However, the difference in MUCCA between the MS and NMOSD groups was not statistically significant ( t=-0.40, P=0.882). In the MS group, MUCCA was an independent predictor of baseline EDSS score (β=-0.03), baseline T25FW score (β=-0.09), and baseline NHPT score (β=-0.30). In the NMOSD group, MUCCA (β=-0.08), age (β=0.06), and baseline EDSS score (β=-0.43) were independent predictors of EDSS progression, and the logistic regression model incorporating these three factors predicted EDSS progression with an AUC of 0.82. Conclusions:Significant spinal cord atrophy occurs in patients with both MS and NMOSD. Atrophy of the upper cervical spinal cord can predict the degree of disability in MS patients and the progression of clinical disability in NMOSD patients.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

Objective:To investigate the structural changes in the spinal cord in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) and their relationship with clinical disability.Methods:This study was cross-sectional. A retrospective analysis of clinical and imaging data from 124 patients with MS (MS group), 101 patients with aquaporin-4 antibody-positive NMOSD (NMOSD group), and 110 healthy controls (HC group) from seven medical centers were conducted from January 2018 to October 2021. All subjects underwent 3D T 1WI, and the upper cervical spinal cord cross-sectional area (MUCCA) was segmented and measured. All patients completed the expanded disability status scale (EDSS) assessments at baseline and during follow-up, as well as the baseline 25-foot walk test (T25FW) and the nine-hole peg test (NHPT). Patients were classified into EDSS progression and non-progression groups based on follow-up EDSS scores. Comparisons of MUCCA among the three groups were conducted using analysis of covariance, controlling for age and sex as covariates. Pairwise comparisons between groups were performed using the HSD test. Univariate linear regression and logistic models were employed to identify candidate predictors of baseline clinical disability status or EDSS progression in the MS and NMOSD groups. L1 regularized multivariable linear regression analysis was used to determine independent predictors of baseline clinical disability status or EDSS progression. Independent predictors were then combined to establish a logistic regression model, and the model′s performance in predicting EDSS progression was evaluated using receiver operating characteristic analysis and the area under the curve (AUC). Results:A total of 144 patients completed follow-up EDSS assessments, with a follow-up duration of 3.30 (1.10, 6.42) years, including 82 patients in the MS group and 62 patients in the NMOSD group. Controlling for sex and age as covariates, the overall difference in MUCCA among the MS, NMOSD, and HC groups was statistically significant ( P=0.001). The MUCCA in the MS group was lower than that in the HC group, with a significant difference ( t=-2.54, P=0.007); the MUCCA in the NMOSD group was also lower than that in the HC group, with a significant difference ( t=-2.80, P=0.002). However, the difference in MUCCA between the MS and NMOSD groups was not statistically significant ( t=-0.40, P=0.882). In the MS group, MUCCA was an independent predictor of baseline EDSS score (β=-0.03), baseline T25FW score (β=-0.09), and baseline NHPT score (β=-0.30). In the NMOSD group, MUCCA (β=-0.08), age (β=0.06), and baseline EDSS score (β=-0.43) were independent predictors of EDSS progression, and the logistic regression model incorporating these three factors predicted EDSS progression with an AUC of 0.82. Conclusions:Significant spinal cord atrophy occurs in patients with both MS and NMOSD. Atrophy of the upper cervical spinal cord can predict the degree of disability in MS patients and the progression of clinical disability in NMOSD patients.

Aim To explore the effect of cuminaldehyde in cumin fruit on gastric ulcer and the protective mechanism via establishing the gastric ulcer model of rats was by ethanol injury. Methods Thirty-six male R. norregicus were divided into six groups: control group, model group, omeprazole positive control group and cuminaldehyde low, medium and high dosage groups. After seven days of continuous intragastric administration, the acute gastric ulcer of R. norregicus was tested by absolute alcohol. Gastric ulcer area, inhibition rate, gastric tissue antioxidant activity, serum inflammatory factors and gastric mucosal protective factors were detected in different groups. Results The results showed that cuminaldehyde significantly reduced the area of gastric ulcer and increased the inhibition rate of gastric ulcer. The inhibition rate of cuminaldehyde at high dose group was up to 74.65%, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH) in gastric tissue significantly increased, and the contents of serum prolandin E

Proportion and rate have multiple and overlapping meanings, which blur their concepts. Based on the existence of the states and the occurrence of the events and their measuring process, we first put forward the concept of "cumulative number of states in point time". Considering the general meaning of "rate" in mathematics and the units of the elements in indexes, this paper puts forward the concept of "the change of cumulative number of states in point time", which is equal to the commonly acknowledged concept "number of incident event within observation period" or "absolute rate", and further constructs relative rate and proportion. Proportions can be classified into three types: time-point (or rate-type) constitutional proportion, time-period incidence proportion and their synthesis, time-period constitutional proportion. The essential difference between relative rate and time-period proportions is whether the observation period is regarded as a one-unit-length fixed period which would be further moved to the description of the indexes. Furthermore, the sources populations of relative rate and proportions are exclusively those at the beginning of the observation period. Thus, we established a unified identification route about ratios, proportions, and rates, the basic indicators of categorical data in populations. These are applicable to both fixed and dynamic populations. The paper aims to clarify the connotation of the indexes and the feasible understanding route and provide some reference for the population researchers.
Humans ; Incidence

Tumor immune therapy has been remarkably successful in recent years and several kinds of PD-1/PD-L1 (programmed death-1/programmed death-ligand 1) antibody drugs have been approved by the FDA for treatment of advanced malignant neoplasms. However, as biomacromolecules these antibody drugs have certain drawbacks such as high cost, injection-only administration and immunogenicity; thus, we turned to small molecules that have lower immune risks and better modifiability. Considering the structural diversity of natural products, we chose to investigate the active components in Panax ginseng, a famous and highly valued traditional Chinese medicine. Nine compounds were separated and identified in this research using a HPLC-coupled MS system, and 3 PD-1 binding compounds were identified using the SPR method. The PD-1/PD-L1 inhibitory ability of ginsenoside Rg₁, as a representative ginsenoside, was verified by cytopharmacological methods. This research provides a new method for the identification of immune blockade inhibitors in natural products.

Objective Changes in the number and function of myeloid-derived suppressor cells (MDSC) were reported in clinical and experimental Sjögren’s syndrome (SS), whereas the underlying mechanisms of MDSCs in SS remain to be elucidated. This study was to observe the changes in the pathologic structure and function of the submandibular gland and salivary flow in SS mice after adoptive transfer or deletion of MDSCs and explore the action mechanisms of MDSCs. Methods Ten 4-week-old non-obese diabetic (NOD) mice (without SS-like symptoms) received adoptive transfer of purified MDSCs at 1×10⁶ per mouse (the MDSC group, n = 5) or injection of PBS (the PBS group, n = 5). Another ten 10-week-old NOD mice were injected intraperitoneally with anti-Gr1 antibodies (the anti-Gr1 group, n = 5) or commensurable Rat IgG2b isotype antibodies (the Rat IgG2b group, n = 5). At 2 weeks after treatment, we determined the salivary flow rate, examined lymphocytic infiltration in the submandibular glands, and counted the MDSCs on Th2 cells in different groups of the mice. Results Compared with the PBS group, the NOD mice of the MDSC group showed significantly reduced Th2 cells in the peripheral blood ([0.67 ± 0.13] % vs [0.16 ± 0.07] %, P < 0.05) and spleen ([0.80 ± 0.13] % vs [0.37 ± 0.04] %, P < 0.05) and salivary flow ([78.70 ± 6.80] vs [33.85 ± 11.25] µL, P < 0.05), but increased numbers of MDSCs in the peripheral blood ([1.54 ± 0.14] vs [5.47 ± 1.54] ×10⁵, P < 0.05) and spleen ([1.09 ± 0.23] vs [4.50 ± 1.04] ×10⁵, P < 0.05). In comparison with the Rat IgG2b group, the animals of the anti-Gr1 group exhibited remarkably decreased Th2 cells in the peripheral blood ([0.55 ±0.09] % vs [0.92 ± 0.10] %, P < 0.05) and spleen ([0.63 ± 0.08] % vs [1.10 ± 0.06] %, P < 0.05) and salivary flow ([56.48 ± 14.18] vs [121.20 ± 10.34] µL, P < 0.05), as well as decreased numbers of MDSCs in the peripheral blood ([1.53 ± 0.12] vs [0.35±0.16] ×10⁵, P < 0.05) and spleen ([2.53 ± 1.10] vs [0.91±0.07] ×10⁵, P < 0.05). The adoptive transfer of MDSCs aggravated while the injection of anti-Gr1 antibodies attenuated lymphocytic infiltration in the submandibular gland of the mice. Conclusion MDSCs participate in the pathogenesis Sjögren’s syndrome by suppressing the response of Th2 cells, which suggests that increasing the response of Th2 cells by inhibiting MDSCs could be a novel target for the treatment of Sjögren’s syndrome.

The aim of this study was to investigated the biological diversity, antibacterial activites and the plant growth-promoting traits of endophytic fungi of sandal (Santalum album), and to assess their potential in the development of antibacterial substances and rapid cultivation of sandal. The results of isolation and taxa analysis of endophytic fungi from sandal showed that 325 strains of endophytic fungi belonging to 16 genera of endophytic fungi were isolated from sandal (of which 86 from roots, 105 from stems and 134 from leaves). The isolation rate and colonization rate of endophytic fungi in different sandal parts showed the same pattern of change: leave>stems>roots. The diversity index of endophytic fungi in sandal roots was significantly higher than that of stems and leaves. The dominant endophytic fungi of sandal roots, stems and leaves showed significant differences. The dominant endophytic fungi of roots were Fusarium (50.00%) and Alternaria (10.47%), Alternaria (58.11%) and Acremonium (20.00%) for stems, and Pantoea (74.63%) for leaves. The antibacterial activity of 40 representative strains of sandal endophytic fungi were analyzed and the results showed that 90% of endophytic fungi exhibited inhibitory activity against at least one of the tested bacteria strains, and the strains with inhibitory activity to Escherichia coli, Enterobacter aerogenes, Shigella dysenteriae, Salmonella typhimurium, Staphylococcus aureus, and Bacillus subtilis accounted for 45.0%, 30%, 47.5%, 55%, 72.5%, and 62.5%, respectively. The sandal fungal endophytes with plant growth-promoting characteristics were screened, and 5 strains of endophytic fungi with phosphorus-solubilizing activity, 8 strains of endophytic fungi producing IAA, and 4 strains of endophytic fungi producing siderophores were found. Among them, endophytic fungus Monilia sp TXRF45 clould produced IAA and siderophores, and also show phosphate-solubilizing activity. The results indicated that the endophytic fungi of Sandal were rich in species diversity and their distribution had a certain tissue specificity. Some strains showed good antibacterial activity and growth-promoting properties, which could potentially applicable for the development of antibacterial substances and rapid cultivation of sandal.

Objective To study the inhibitory effect of Tilianin on non -small cell lung cancer cell lines (A549) and the associated mechanisms.Methods The control group and 10,20,40,80 and 160 μmol· L-1 experimental group were treated with 0,10,20,40,80 and 160 μ mol· L-1Tilianin for 24 h,cell proliferation and toxicity test kit (CCK8) was used to observe the proliferation of A549 cells.The apoptosis of A549 cells in each group was detected by flow cytometry.In the hypoxia model group,A549 cells were cultured in hypoxic incubator for 4 h.In the hypoxia experimental group of 10,20 and 40 μmol · L-1Tilianin,A549 cells were pretreated with 10,20 and 40 μmol · L-1Tilianin for 4 h,and then cultured in hypoxic incubator for 4 h.Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) was used to detect the gene expressions of vascular endothelial growth factor(VEGF) and HIF-1α (HIF-1α).The protein expressions of VEGF-A,HIF-1α and p-Akt were detected by Western blot.Results Compared with control group,Tilianin significantly inhibited the proliferation of A549 in a dose -dependent manner.The inhibitory rates of proliferation of 10,20,40,80 and 160 μmol · L-1 experimental groups were (5.83 ±1.67)％,(6.77 ±0.87)％,(12.26 ±0.23)％,(22.97 ±0.50)％ and (46.24±1.44)％,the difference was statistically significant (P ＜0.05).The apoptosis rates of 10,20,40,80 and 160 μmol · L-1Tilianin were (6.80 ±0.62)％,(14.70 ±1.36)％,(24.76 ±4.37)％,(39.26±6.42)％ and (62.31 ±1.79)％,respectively,compared with the control group,the differences were statistically significant (P ＜ 0.05).In the hypoxia model group,the gene expression of HIF-1α was 4.30 ± 0.26,VEGF expression was 6.02 ± 0.53,compared with the control group,the differences was statistically significant (P ＜0.05).In 10,20,40 μmol · L-1Tilianin hypoxia experiment group,the gene expression of VEGF were 4.73 ±0.20,2.31 ±0.09 and 1.47 ±0.16,respectively.The expression of HIF-1α were 3.01 ± 0.11,1.81 ± 0.13 and 1.03 ± 0.16.Compared with hypoxia model group,the differences was statistically significant (P ＜ 0.05).The expression of p-AKT protein in hypoxic model group was (106.47 ± 2.08)％,the expression of HIF-1αwas (204.31 ± 8.35)％,the expression of VEGF-A was 212.30 ±4.80.The expression of p-AKT protein in 10,20,40 μmol · L-1 hypoxic experimental group were (87.51 ±2.72)％,(75.18 ± 1.67)％ and (32.40 ± 0.86)％,the protein expression levels of HIF-1α were (182.54 ± 6.42),(90.95 ± 2.76)％,(15.03 ± 4.21)％,the protein expression of VEGF-A were (156.38 ± 5.12) ％,(79.62 ± 2.84) ％ and (13.72 ± 4.64) ％,with significant difference (P ＜ 0.05).Conclusion Tilianin has the effect of inhibiting the proliferation and inducing apoptosis of A549 in vitro through AKT / HIF-1α signaling pathway.