ObjectiveTo investigate how Xiaoyao Shukun decoction （XYSKD） regulates the formation and release of neutrophil extracellular traps （NETs） via the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway， thereby reducing inflammation， inhibiting the excessive proliferation of fibroblasts in pelvic adhesion tissue， decreasing adhesion and fibrosis， and repairing the tissue damage in sequelae of pelvic inflammatory disease （SPID）. MethodsA total of 84 Wistar rats were randomly allocated into seven groups： blank， model， XYSKD （8 mg·kg^-1）， mTOR agonist （10 mg·kg^-1）， mTOR agonist + XYSKD （10 mg·kg^-1+8 mg·kg^-1）， mTOR inhibitor （2 mg·kg^-1）， and mTOR inhibitor + XYSKD （2 mg·kg^-1+8 mg·kg^-1）. The rat model of SPID was constructed by starvation， fatigue， and ascending Escherichia coli infection. After 14 days of drug intervention， the ultrastructure of fibroblasts in the pelvic adhesion tissue was observed by transmission electron microscopy. The general morphology of the uterus， fallopian tube， and ovary was observed by laparotomy. The levels of interleukin-1β （IL-1β）， interleukin-17 （IL-17）， and tumor necrosis factor-α （TNF-α） in the peritoneal flushing fluid were determined by enzyme-linked immunosorbent assay （ELISA）. The expression of myeloperoxidase （MPO） and citrullinated histone 3 （H3） in the fallopian tube was detected by immunofluorescence. Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR） were employed to determine the relative protein and mRNA levels， respectively， of neutrophil elastase （NE）， intercellular adhesion molecule-1 （CD54）， α-smooth muscle actin （α-SMA）， H3， PI3K， and Akt. ResultsCompared with the blank group， the model group presented a large number of collagen fibers in bundles， numerous cytoplasmic folds of fibroblasts， reduced or absent mitochondrial cristae， and disordered and expanded endoplasmic reticulum. By laparotomy， extensive pelvic congestion， connective tissue hyperplasia， thickening and hardening of the tubal end near the uterus， and tubal and ovarian adhesion or cyst were observed in the model group. In addition， the model group showed raised levels of IL-1β， IL-17， and TNF-α in the peritoneal flushing fluid （P<0.01）， increased average fluorescence intensities of MPO and H3 （P<0.01）， and up-regulated protein and mRNA levels of NE， H3， CD54， PI3K， and Akt （P<0.01）. Compared with the model group， the mTOR agonist group showed increased fibroblasts and cytoplasmic folds， absence of mitochondrial cristae， endoplasmic reticulum dilation， and evident collagen fiber hyperplasia. Pelvic adhesions were observed to cause aggravated damage to the uterine， fallopian tube， and ovarian tissues. The levels of IL-1β， IL-17， and TNF-α in the peritoneal lavage fluid elevated （P<0.01） and the average fluorescence intensities of MPO and H3 enhanced （P<0.01） in the mTOR agonist group. In contrast， the XYSKD group and the mTOR inhibitor group showcased decreased fibroblasts and collagen fibers， alleviated mitochondrial crista loss and endoplasmic reticulum dilation， improved morphology and appearance of the uterine， fallopian tube， and ovarian tissues， lowered levels of IL-1β， IL-17， and TNF-α in the peritoneal lavage fluid （P<0.01）， decreased average fluorescence intensities of MPO and H3 （P<0.01）， and down-regulated protein and mRNA levels of NE， H3， CD54， PI3K， and Akt （P<0.05）. Compared with the mTOR agonist group， the mTOR agonist + XYSKD group showed alleviated pathological changes in the pelvic tissue， declined levels of IL-1β， IL-17， and TNF-α （P<0.01）， decreased average fluorescence intensities of MPO and H3 （P<0.01）， and down-regulated protein levels of NE， H3， CD54， α-SMA， p-PI3K/PI3K， and p-Akt/Akt （P<0.01） and mRNA levels of NE， H3， CD54， α-SMA， PI3K， and Akt （P<0.01）. Compared with the mTOR inhibitor group， the mTOR inhibitor + XYSKD group demonstrated reduced pathological severity of the pelvic tissue， reduced levels of IL-1β， IL-17， and TNF-α （P<0.01）， decreased average fluorescence intensities of MPO and H3 （P<0.01）， and down-regulated protein and mRNA levels of NE and CD54 （P<0.05）. ConclusionXYSKD can inhibit the excessive formation and release of NETs via PI3K/Akt/mTOR to ameliorate the inflammatory environment and reduce fibrosis and adhesion of the pelvic tissue， thereby playing a role in the treatment of SPID. It may exert the effects by lowering the levels of IL-1β， IL-17， and TNF-α and down-regulating the expression of NE， H3， CD54， α-SMA， PI3K， and Akt in the pelvic adhesion tissue.

Objective To observe the effects of Angelicae Sinensis Radix-Paeoniae Radix alba combined with bone marrow mesenchymal stem cells(BM-MSCs)transplantation on liver inflammation and hepatocytes regeneration in non-alcoholic steatohepatitis(NASH)associated cirrhosis;To discuss its possible mechanism.Methods West diet combined with carbon tetrachloride was used to prepare the NASH related cirrhosis model.The mice were randomly divided into control group,model group,Angelicae Sinensis Radix-Paeoniae Radix alba group,BM-MSCs group,and Angelicae Sinensis Radix-Paeoniae Radix alba+BM-MSCs group,with 12 mice in each group.After successful modeling,corresponding interventions were given according to grouping for 4 consecutive weeks.HE staining was used to observe the morphology of liver tissue;the contents of serum ALT,AST,TBil,TG,ALB,AFP,as well as the contents of IL-1β,TNF-α and HGF in liver tissue were detected;RT-qPCR was used to detect TLR9,MyD88,TRAF6 and NF-κBp65 mRNA expression in liver cells;primary liver cells were separated,CpG ODN 2216 stimulation was induced in vitro,cells supernatant was extracted,and IL-1β and TNF-α content were detected.Results Compared with the control group,inflammatory cell infiltrated in liver tissue of model group mice,accompanied by hepatocyte necrosis and collagen deposition,forming pseudo lobules;the contents of serum ALT,AST,TBil and TG increased,the content of ALB decreased,the content of HGF in liver tissue decreased,the contents of IL-1β and TNF-α increased,with statistical significance(P<0.05);the mRNA expressions of TLR9,MyD88,TRAF6 and NF-κBp65 in liver cells increased(P<0.05),and the contents of IL-1β and TNF-α in cells supernatant increased after CpG ODN 2216 induction(P<0.05).Compared with the model group,the inflammatory infiltration in liver tissue and necrosis of liver cells were reduced and the degree of liver fibrosis was alleviated in the Angelicae Sinensis Radix-Paeoniae Radix alba+BM-MSCs group,the liver tissue damage in Angelicae Sinensis Radix-Paeoniae Radix alba group and BM-MSCs group were slightly improved;except for the TG content in BM-MSCs group,all detection indicators showed significant improvement in each intervention group(P<0.05).Compared with the Angelicae Sinensis Radix-Paeoniae Radix alba group and BM-MSCs group,the Angelicae Sinensis Radix-Paeoniae Radix alba+BM-MSCs group showed statistical significance in related detection indicators(P<0.05),and demonstrated a synergistic effect.Conclusion Angelicae Sinensis Radix-Paeoniae Radix alba combined with BM-MSCs transplantation could effectively improve the liver function and promote liver cell regeneration.The mechanism is associated with the down-regulation of TLR9/NF-κB signaling pathway expressions and function,the inhibition of inflammatory cytokines secretions,and the improvement of liver inflammatory microenviroment.

AIM:To evaluate corrective effect and stability of corneal morphology in patients with moderate to high myopia after 2a treatment of femtosecond laser assisted laser in situ keratomileusis(FS-LASIK)Xtra.METHODS:Retrospective case-control study. A total of 30 cases(58 eyes)Patients with moderate to high myopia combined with astigmatism who planned to undergo refractive surgery in our hospital from August 2019 to August 2020 were included, and different types of surgery were performed respectively based on the relevant index of keratoconus screening in the preoperative corneal topography. They were divided into FS-LASIK group and Xtra group, with 15 cases(29 eyes)in each group. Uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), spherical equivalent(SE)and the corneal curvature of the anterior and posterior surfaces of different diameters(3, 5 and 7 mm)measured by Sirius three-dimensional corneal topography were observed preoperatively and 3 mo, 1 and 2 a postoperatively.RESULTS: The UCVA of the two groups of patients at different time points after surgery was significantly increased compared with preoperatively(both P<0.01), and there was no difference in UCVA and SE between the two groups(P>0.05). After 2 a postoperatively, residual astigmatism was -0.25-0 D in 25 eyes(86%)of the FS-LASIK Xtra group and 24 eyes(83%)of the FS-LASIK group. The actual corrected SE and expected corrected SE of both groups were positively correlated(both P<0.05). There were differences in corneal curvature on the surface of different diameter areas(3, 5, and 7 mm)between the two groups at 3 mo, 1, and 2 a postoperatively compared with preoperatively. After 1 and 2 a postoperatively, the corneal posterior surface curvature of the FS-LASIK Xtra group with corneal diameter of 3 and 5 mm was higher than that of the FS-LASIK group(P<0.05).CONCLUSIONS:FS-LASIK Xtra has good safety, efficacy and predictability in correcting patients with moderate to high myopia.

Objective:To learn about the epidemic dynamics and spatial epidemic characteristics of human brucellosis in Gansu Province.Methods:Data on human brucellosis in Gansu Province reported by China Disease Control and Prevention Information System from January 2016 to December 2020 were collected and analyzed by descriptive epidemiology and spatial clustering analysis.Results:A total of 10 025 cases of human brucellosis were reported in Gansu Province from 2016 to 2020, with a statistically significant difference in incidence rate between years (χ 2 = 242.86, P = 0.001). The incidence was the lowest in 2018 (6.03/100 000), and the highest in 2020 (11.39/100 000). The reported cases were concentrated in 45 - 55 years old, accounting for 34.52% (3 461/10 025); the male to female ratio was 2.91 ∶ 1.00 (7 458/2 567); farmers were the main occupation, accounting for 82.11% (8 232/10 025). Among the 86 counties (cities, districts) in Gansu Province, Yongchang County had the highest number of reported cases in 2020 (339 cases), and Sunan Yugur Autonomous County had the highest incidence in 2020 (190.89/100 000). Spatial autocorrelation analysis showed that there was significant spatial positive correlation between the incidence rate of human brucellosis in Gansu Province from 2016 to 2020 (global Moran's I > 0, Z > 1.96, P < 0.05), showing a spatial clustering distribution. The high-high clustering areas were concentrated in Yongchang County and Sunan Yugur Autonomous County. Conclusion:In Gansu Province, the main population of human brucellosis is middle-aged male farmers, and the incidence of brucellosis is spatially clustered.

Abstract: Objective To conduct a molecular epidemiological tracing and analysis of Yersinia pestis strains isolated from two human plague outbreaks with unknown sources in Gansu Province, China. The results of this analysis would provide a basis for isolating and controlling the sources of Yersinia pestis. Methods The strains of Yersinia pestis isolated from two human plague outbreaks occurring on December 12, 2017, and September 27, 2019 were genotyped by the different region (DFR) and the clustered regularly interspaced short palindromic repeats (CRISPR). The repeat numbers of the variable number tandem repeat (VNTR) loci in the tested strains of Yersinia pestis were calculated by the multiple variable number tandem repeats analysis (MLVA), and the location of the phylogenetic tree of the tested strains was determined with the method of minimum spanning tree (MST) by the software BioNumerics 6.6. Results The strain of 20171212 lacked DFR01, DFR02, DFR03, DFR04, DFR13, DFR23, and the DFR type was identified as type 8. The space sequence of YPa was a1'-a2-a3-a4-a5-a6-a7-a35, the space sequence of YPb was b1-b2-b3-b4, the space sequence of YPc was c1-c2-c3, the gene cluster of CRISPR was Ca35', the genotype of CRISPR was 26'. MLVA clustering analysis showed that the strain clustered within in the cluster of Yuerhong pasture in Subei County and formed an independent branch. On the other hand, the strain of 20190927 lacked DFR01, DFR13 and DFR23, with the DFR type identified as type 1b. The space sequence of YPa was a1-a2-a3-a4-a5-a6-a7, the space sequence of YPb was b1-b2-b3-b4, the space sequence of YPc was c1-c2-c3, the gene cluster of CRSIPR was Ca7, the genotype of CRSIPR was 22 MLVA clustering analysis showed that the strain was located close to the cluster of Dangjinshan in Akesai County, and relatively distant from the cluster of Yuerhong pasture in Subei County. Conclusions The genotypes of strain 20171212 by DFR and CRISPR were consistent with the main genotypes of Y. pestis from Himalayana Marmota foci in Subei County, which confirmed that the human plague cases were naturally occurring locally. However, the strain gathered the cluster of Yuerhong pasture in Subei County, which indicated that the source of infection was not in Yanchiwan Town, but in the surrounding area of the Yuerhong pasture. The genotypes of strain 20190927 by DFR and CRISPR were in accordance with the main genotype of Y. pestis from Himalayana Marmota foci in Akesai County and were closer to the cluster of Dangjinshan in Aksai County than to

Objective:To study the epidemiological characteristics of human brucellosis in high incidence areas of brucellosis in Gansu Province, and provide a guidance for precise prevention and control of brucellosis in the areas with high incidence of the disease.Methods:Using a retrospective research method, human brucellosis monitoring data from five high incidence counties of brucellosis in Gansu Province from 2018 to 2020, including Huan County (eastern), Guazhou County (western), Zhangjiachuan County (southern), Gaotai County (northern), and Jingtai County (central), were collected from monitoring database of the Central Transfer Payment Project. The epidemic characteristics of brucellosis in high incidence areas were described and analyzed.Results:From 2018 to 2020, there were a total of 787 laboratory confirmed cases of brucellosis in high incidence areas of brucellosis in Gansu Province, with a prevalence rate of 3.64%. The incidence rates for each year were 2.63% (205/7 780), 4.60% (327/7 111), and 3.78% (255/6 746), with statistically significant differences between different years (χ 2 = 41.44, P < 0.001). The prevalence rates of brucellosis in Huan County, Guazhou County, Zhangjiachuan County, Gaotai County, and Jingtai County were 0.02% (1/4 263), 3.67% (140/3 817), 4.32% (182/4 209), 4.89% (237/4 847), and 5.04% (227/4 501), respectively. There was a statistically significant difference in comparison between different regions (χ 2 = 211.59, P < 0.001). In 2018, the incidence rate was highest in Jingtai County in the central region, and scattered to Zhangjiachuan County in the south and Gaotai County in the north in 2019 and 2020. There were statistically significant differences in the prevalence rates among different genders, ages, ethnicities, educational levels, and occupational groups (χ 2 = 111.95, 212.76, 35.32, 89.59, 97.93, P < 0.001). From 2018 to 2020, the incidence of brucellosis in the < 20 (0.78%, 6.36%, 10.00%), 40 - 50 age groups (5.15%, 7.03%, 8.00%), students and young children (0.58%, 9.20%, 13.64%), and cadres (2.86%, 4.55%, 10.53%) showed an increasing trend year by year (χ 2trend = 21.55, 7.00, 30.63, 2.01, P < 0.001). Conclusions:The brucellosis in Gansu Province is still in a high level of growth stage, and the epidemic area is gradually dispersing; the cases are gradually becoming younger, and key occupational personnel are shifting from farmers and herdsmen to social workers. It is recommended to increase the scope of monitoring, increase publicity efforts, and enhance the self-protection and control awareness of key populations.

Objective:To study the genotyping and regional distribution characteristics of Yersinia pestis by single nucleotide polymorphism (SNP) in Gansu Province. Methods:A total of 52 strains of Yersinia pestis isolated from Himalaya Marmot plague foci and Spermophilus alaschanicus plague foci in Gansu Province from 1962 to 2017 were selected for culture and extraction of DNA. The genomic DNA of Yersinia pestis was sequenced by the second generation of Illumina PE150 to identify the SNP sites. The species characteristics of Yersinia pestis in Gansu Province was determined by the Kimura-2-parameter model of neighbor joining of Mega 10.0 software based on the SNP sites. The molecular evolutionary tree of the groups was determined by Hasegawa-Kishino-Yano model of maximum likelihood method according to the SNP sites. Results:A total of 103 SNP sites were identified in 52 strains of Yersinia pestis in Gansu Province, including 28 intergenic loci, 43 non-synonymous mutations, 31 synonymous mutations and 1 nonsense mutation. The 52 strains of Yersinia pestis were divided into 2 biotypes and 3 groups, which were ancient type (1.IN2, 3.ANT) and medieval type (2.MED). Among them, 35 strains belonged to 1.IN2 group, 13 strains belonged to 3.ANT group, and 4 strains belonged to 2.MED group. The 1.IN2 group was further divided into 5 subgroups: the groups of Yuerhong Town and Dangchengwan Town in Subei County, the groups of Mati Town and Dahe Town in Sunan County, and the group of Xiahe County. The 3.ANT group was further divided into 2 subgroups: the groups of Hongliuwan Town in Aksay County and Machang in Dangchengwan Town of Subei County. Conclusion:The SNP method can be used to genotype Yersinia pestis from different plague foci in Gansu Province, which has certain regional characteristics.

Objective:To analyze the changes of spatial, seasonal, and age distribution of brucellosis among humans and animals in Gansu Province and to provide a reference for the next step in formulating prevention and control measures.Methods:Reported data of brucellosis of humans and animals in Gansu Province from 2018 to 2020 were collected. The human epidemic data were obtained from "China Disease Control and Prevention Information System", and the positive data of animals were obtained from the monthly report provided by Gansu Animal Disease Control Center. Human brucellosis was classified and analyzed according to year, month, age and region, and livestock brucellosis was classified according to year, month, population and region. ArcGIS 10.2 software was used to analyze the spatial epidemiological characteristics of the data. Measuring Geographic tool was used to calculate the shifting distance of the center of the disease incidence in humans and animals from 2018 to 2020.Results:From 2018 to 2020, a total of 6 375 cases of human brucellosis were reported in Gansu Province. The 40 - 59 age group accounted for 54.96% (3 504/6 375), 1 584 cases were reported in 2018, 1 787 cases were reported in 2019, and 3 004 cases were reported in 2020. The high incidence time of human brucellosis was July and November. A total of 48 180 brucellosis-positive animals (heads) were detected, of which 47 342 were positive sheep, accounting for 98.26% (47 342/48 180). The high incidence time of brucellosis among animals was October. Among the 14 cities (prefectures), the top cities of livestock brucellosis reported were Qingyang City, Zhangye City and Jiuquan City. The center of disease incidence among humans was located in Gulang County, Wuwei City. The center of disease incidence among animals was located in Wuwei City in 2018 and Qingyang City in 2020.Conclusions:The cases of brucellosis in humans and animals in Gansu Province are on the increase. In some areas, there are problems of separation of human and animal epidemics. It is necessary to actively strengthen monitoring and implement measures to prevent and control brucellosis in humans and animals in high-risk areas to curb the spread of the epidemic.

Plague natural foci in Gansu Province are large in area and widely distributed, and the epidemic status is different in each focus. Some plague natural foci have been resting for many years and are under stable control. In other plague natural foci, the epidemic of plague among animals is relatively active, and dozens of strains of Yersinia pestis can be isolated every year. The plague among animals spreads to the humans from time to time, and the cases of human plague are more severe, short in course of disease, and high in mortality. In recent years, with the sharp increase of migrant workers engaged in grazing and engineering construction in plague natural foci, opportunities to actively contact infected animals such as marmots, hares and sheepdogs have increased, resulting in an increase of human plague cases. In addition, the behaviors of illegal hunting, trafficking and sale of marmots cannot be stopped, resulting in human plague throughout the year. Therefore, the party committees and governments at all levels and the health administrative departments in Gansu Province have formulated the plague prevention and control measures suitable for this region according to the epidemic characteristics of plague among animals and humans. In this paper, the characteristics of plague epidemic situation at present and the prevention and control measures adopted in Gansu Province are discussed, in order to provide scientific basis and guidance for optimizing plague prevention and control measures in the future.

Objective:To evaluate the predictive value of the serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration for postoperative acute kidney injury (AKI) in neonates undergoing cardiac surgery.Methods:Perioperative data of 110 consecutive neonates (≤28 days) who underwent cardiac surgery in our hospital from October 2017 to May 2021, were collected retrospectively.According to pROCK criteria, the patients were divided into AKI group and non-AKI group.Demographics, predominant diagnosis, laboratory examination, perioperative management and postoperative outcomes were compared between two groups.The concentration of serum NT-proBNP was routinely measured within 12 h after operation.Multivariate logistic regression analysis was performed for the association between serum NT-proBNP and postoperative AKI.Receiver operating characteristic curve was drawn, and the predictive value of serum NT-proBNP for postoperative AKI was determined according to the area under the curve.Results:A total of 106 neonates were enrolled, and the incidence of postoperative AKI was 54.7%.There were significant difference in the baseline hemoglobin concentration, hematocrit and serum creatinine and serum NT-proBNP concentration between AKI group and non-AKI group ( P<0.05). Multivariate logistic regression analysis indicated that NT-proBNP level was an independent risk factor for AKI after cardiac surgery in neonates ( odds ratio 2.49, 95% confidence interval 1.183-5.23, P=0.016). The area under the curve of NT-proBNP predicting AKI after cardiac surgery was 0.66 (95% confidence interval 0.56-0.76, P=0.007). Conclusions:Elevated serum NT-proBNP concentration is an independent risk factor for AKI after cardiac surgery in neonates and has a certain predictive value for AKI, and close monitoring of perioperative NT-proBNP level is helpful for early identification of high-risk neonates.