Objective To investigate the therapeutic effect of Neferine on acute lung injury in sepsis rats and its mechanism.Methods A rat sepsis model was prepared by cecal ligation and puncture(CLP)method.After successful modeling,the rats were divided into model group,neferine low-and high-dose groups,neferine high-dose+PMA[nuclear factor kappa B(NF-κB)activator phorbol ester]group,and sham operation group was set up,with 15 rats in each group.At 6 hours after operation,the corresponding intervention was given for 2 days.Hematoxylin-eosin(HE)staining was used to observe the morphological changes of lung tissue,and the pathological damage score was performed.The wet-dry mass ratio of lung tissue was detected;the levels of arterial partial pressure of oxygen(PaCO2)and arterial partial pressure of carbon dioxide(PaCO2)were detected by blood gas analyzer.The levels of tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β)and interleukin 6(IL-6)in bronchoalveolar lavage fluid(BALF)were measured by enzyme-linked immunosorbent assay(ELISA).The protein expression levels of NF-κB p65,phosphorylated NF-κB(p-NF-κB)p65(Ser536)and cyclooxygenase-2(COX-2)in lung tissue were detected by Western Blot.Results Compared with the sham operation group,the pathological injury of lung tissue in the model group was severe,the pathological injury score and wet-dry mass ratio of lung tissue as well as PaCO2 level were significantly increased(P＜0.01),PaO2 level was significantly decreased(P＜0.01),the levels of TNF-α,IL-1β and IL-6 in BALF,the ratio of p-NF-κB p65/NF-κB p65 and the protein expression level of COX-2 in lung tissue were significantly increased(P＜0.01).Compared with the model group,the pathological damage of lung tissue in the low-dose and high-dose neferine groups was significantly improved,the pathological damage score and wet-dry mass ratio of lung tissue as well as PaCO2 level were significantly decreased(P＜0.05 or P＜0.01),PaO2 level was significantly increased(P＜0.05 or P＜0.01),the levels of TNF-α,IL-1β and IL-6 in BALF,the ratio of p-NF-κB p65/NF-κB p65 and the protein expression level of COX-2 in lung tissue were significantly decreased(P＜0.05 or P＜0.01).However,after PMA intervention,the improvement of neferine on lung tissue injury in septic rats was significantly reversed(P＜0.01).Conclusion Neferine can improve acute lung injury and lung function in rats with sepsis,which may be related to inhibiting the activation of NF-κB signaling pathway and thereby reducing the release of inflammatory factors in vivo.

Investigating the species/biovars,distribution patterns,and genetic correlations of Brucella from sheep in north-west China is critical to reveal the population and epidemiological characteristics of the Brucella melitensis.In this study,con-ventional identification and AMOS-PCR were used to determine the species/biovars of Brucella isolated from 13 regions in northwest China.MLST and MLVA-16 genotyping methods were used to analyze the genetic characteristics of the strains.Con-ventional identification and AMOS-PCR detection revealed that 59 Brucella melitensis were isolated in this study,in-cluding 22 strains from Inner Mongolia,17 strains from Xin-jiang,13 strains from Gansu,and 7 strains from Qinghai,of which 58 strains were B.melitensis biovar 3,and one strain was B.melitensis biovar 1.MLST analysis indicated that 90％(53/59)of B.melitensis were of ST8 sequence type,the dominant epidemic population.The MLVA-11 survey demonstrated that 59 B.melitensis strains clustered into six MLVA-11 genotypes,and 87％of the strains were of MLVA-11 genotype 116.Therefore,the predominant strains in the northwest region were from the Eastern Mediterranean lineage.MLVA-16 divided 59 strains of B.melitensis into 40 gen-otypes,eight of which were shared genotypes.Each genotype was composed of two to seven strains from the same region,thereby indicating that the cases of each shared genotype were outbreaks from a common source of infection.All shared MLVA-16 genotypes comprised strains from the same province,thus indicating apparent regional clustering characteristics of strains in each province.In a genetic comparison between populations and isolated strains from the spleens of sheep,multiple identical MLVA-16 genotypes were found to be composed of strains from different hosts.These findings indicated a transmission path-way from sheep/goats to humans.B.melitensis biovar 3 was the main pathogen causing animal brucellosis in the northwest re-gion,and infected sheep were the main brucellosis infection source in the regional population.The ST8 strains were the domi-nant epidemic population,and the MLVA genotype of strains in each region showed clear regional clustering characteristics.

This study aims to provide evidence for clinical practice by systematically reviewing the efficacy and safety of Gusongbao preparation in the treatment of primary osteoporosis(POP). The relevant papers were retrieved from four Chinese academic journal databases and four English academic journal databases(from inception to May 31, 2022). The randomized controlled trial(RCT) of Gusongbao preparation in the treatment of POP was included after screening according to the inclusion and exclusion criteria. The quality of articles was evaluated using risk assessment tools, and the extracted data were subjected to Meta-analysis in RevMan 5.3. A total of 657 articles were retrieved, in which 15 articles were included in this study, which involved 16 RCTs. A total of 3 292 patients(1 071 in the observation group and 2 221 in the control group) were included in this study. In the treatment of POP, Gusongbao preparation+conventional treatment was superior to conventional treatment alone in terms of increasing lumbar spine(L2-L4) bone mineral density(MD=0.03, 95%CI[0.02, 0.04], P<0.000 01) and femoral neck bone mineral density, reducing low back pain(MD=-1.69, 95%CI[-2.46,-0.92], P<0.000 1) and improving clinical efficacy(RR=1.36, 95%CI[1.21, 1.53], P<0.000 01). Gusongbao preparation was comparable to similar Chinese patent medicines in terms of improving clinical efficacy(RR=0.95, 95%CI[0.86, 1.04], P=0.23). Gusongbao preparation was inferior to similar Chinese patent medicines in reducing traditional Chinese medicine syndrome scores(MD=1.08, 95%CI[0.44, 1.71], P=0.000 9) and improving Chinese medicine syndrome efficacy(RR=0.89, 95%CI[0.83, 0.95], P=0.000 4). The incidence of adverse reactions of Gusongbao preparation alone or combined with conventio-nal treatment was comparable to that of similar Chinese patent medicines(RR=0.98, 95%CI[0.57, 1.69], P=0.94) or conventio-nal treatment(RR=0.73, 95%CI[0.38, 1.42], P=0.35), and the adverse reactions were mainly gastrointestinal discomforts. According to the available data, Gusongbao preparation combined with conventional treatment is more effective than conventional treatment alone in increasing lumbar spine(L2-L4) bone mineral density and femoral neck bone mineral density, reducing low back pain, and improving clinical efficacy. The adverse reactions of Gusongbao preparation were mainly gastrointestinal discomforts, which were mild.
Humans ; Bone Density ; Low Back Pain ; Medicine, Chinese Traditional ; Osteoporosis/drug therapy*

OBJECTIVES: To analyze the gross pathological data of sudden cardiac death (SCD) with different causes, to provide data support for the identification of sudden cardiac death with unknown causes. METHODS: A total of 167 adult SCD cases in the archive of the Forensic Expertise Institute of Nanjing Medical University from 2010 to 2020 were collected. The gross pathological data of SCD cases were summarized and the characteristics of different causes of death were statistically analyzed. RESULTS: The ratio of male to female SCD cases was 3.4∶1. Coronary heart disease was the leading cause of SCD, and mainly distributed in people over 40 years old. SCD caused by myocarditis was mainly distributed in young people and the mean age of death was (34.00±9.55) years. By analyzing the differences in cardiac pathological parameters of SCD with different causes, it was found that the aortic valve circumference was significantly dilated in the SCD caused by aortic aneurysm or dissection (P<0.05). The heart weight of SCD caused by aortic aneurysm or dissection and combined factors was greater, and both pulmonary and tricuspid valvular rings were dilated in the SCD caused by combined factors in adult males (P<0.05). CONCLUSIONS Various gross pathological measures of SCD with different causes are different, which has reference value in the cause of death identification of SCD.
Humans ; Adult ; Male ; Female ; Adolescent ; Young Adult ; Death, Sudden, Cardiac/pathology* ; Coronary Disease ; Heart ; Forensic Medicine ; Autopsy

The material basis and mechanism of Chaenomelis Fructus in the treatment of rheumatoid arthritis(RA) were explored by network pharmacology, and the potential anti-RA targets of Chaenomelis Fructus were verified by molecular docking and animal experiments. The active components and targets of Chaenomelis Fructus were searched against the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. GeneCards, DisGeNET, and OMIM were used to obtain RA-related targets. The common targets shared by Chaenomelis Fructus and RA were considered as the potential targets of Chaenomelis Fructus in the treatment of RA. Cytoscape 3.9.0 was employed to establish a "traditional Chinese medicine-active component-common target-disease" network. The protein-protein interaction(PPI) network was established by STRING, and the core genes were visualized by RStudio 4.1.0. DAVID was used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict and visualize the involved signaling pathways. Molecular docking was carried out with the active components screened out as ligands and RA core genes as the targets. Finally, the prediction results were verified by animal experiments. Four main active components of Chaenomelis Fructus were obtained, which corresponded to 137 targets. Chaenomelis Fructus and RA shared 37 common targets. GO annotation yielded 239 terms(P<0.05), and KEGG pathway enrichment analysis screened out 94 signaling pathways(P<0.05), mainly involving interleukin-17(IL-17), tumor necrosis factor, Toll-like receptor, and nuclear factor-kappa B(NF-κB) signaling pathways. Molecular docking results showed that the main active components of Chaenomelis Fructus bound well with the core targets of RA. The results of animal experiments proved that Chaenomelis Fructus can alleviate joint swelling in the mice with RA. The results of ELISA showed that Chaenomelis Fructus lowered the levels of interleukin-6(IL-6) and interleukin-1β(IL-1β). Western blot showed that Chaenomelis Fructus down-regulated the protein level of vascular endothelial growth factor A(VEGFA). Chaenomelis Fructus exerts anti-inflammatory effect and reduces pannus formation by regulating the core targets such as VEGFA, IL-1β, and IL6 in the treatment of RA. The findings of this study provide new ideas for the future treatment of RA with Chaenomelis Fructus.
Animals ; Mice ; Network Pharmacology ; Vascular Endothelial Growth Factor A ; Molecular Docking Simulation ; Arthritis, Rheumatoid/genetics* ; Tumor Necrosis Factor-alpha ; NF-kappa B ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional

Aim To study the protective effect of eplerenone on the contralateral kidney in pregnant rats with chronic kidney disease (CKD) and its mechanism. Methods Female Wistar rats were randomly divided into sham-operation group, sham-operation pregnancy group, model group and eplerenone group. The rats in the model group and eplenone group had ligation unilateral ureter, and the rats in the eplenone group were treated with 100 mg • kg

Objective: To evaluate the immunogenicity of group A+C meningococcal polysaccharide conjugate vaccine in infants under 2 years old. Methods: From March 2017 to June 2018, 1 932 healthy infants in Biyang County, Henan Province, who were not vaccinated with meningococcal meningitis vaccine and whose axillary temperature was ≤37.0 ℃, were recruited as participants. The 3 months and 6-11 months old infants were allocated to the experiment group and the control group in a ratio of 1∶1. Infants aged 12-23 months were allocated to the 1-dose group, the 2-dose group and the control group in a ratio of 1∶1∶1, with 276 infants in each group. The infants in the experiment group were intramuscularly injected with freeze-dried group A+C meningococcal polysaccharide conjugate vaccine to be evaluated, and infants in the control group received intramuscular injection of commercially available freeze-dried group A+C meningococcal conjugate vaccine. The venous blood of infants was collected 30 days before the first dose and after the last dose of inoculation, and the antibody seroconversion of each group was determined and compared. Results: The completion rate of immunogenicity study was 95.2% (1 839/1 932). Before inoculation, there was no statistical difference in the geometric mean titer and positive rate of group A+C antibodies between the experiment group and the control group in 3 months and 6-11 months old infants (all P values >0.05). The geometric mean titers and positive rate of group A antibodies in the 1-dose group were higher than those in the control group (all P values <0.05), but there was no statistical difference between the 2-dose group and the control group (all P values >0.05) in infants aged 12-23 months. After inoculation, the differences (95%CI) in the positive conversion rate of group A+C antibodies between the experiment group and the control group were -0.12% (-6.01%-5.77%) and 0.82% (-4.23%-5.86%) in the 3 months old infants. At the age of 6-11 months, the differences were 6.75% (1.71%-11.79%) and -4.32% (-8.73%-0.08%), respectively. At the age of 12-23 months, the differences were 1.02% (-3.80%-5.83%) and -4.40% (-7.79%- -1.01%) in the 2-dose group and -7.22% (-12.90%- -1.54%) and -18.61% (-23.75%- -13.46%) in the 1-dose group, respectively. The geometric mean titers of group A+C antibodies in the 3 months old infants were 48.50 and 63.12, respectively, which had no significant difference from the control group (43.02 and 57.99, respectively) (both P values <0.05). The geometric mean titers of group A+C antibodies in the 6-11 months and 12-23 months old infants were 84.09 and 92.51 (2-dose group), which were higher than those in the corresponding control group (43.10 and 61.83, respectively) (all P values <0.001). Conclusion: Group A+C meningococcal conjugate vaccine has good immunogenicity in infants under 2 years old.
Humans ; Infant ; Child, Preschool ; Meningococcal Vaccines ; Vaccines, Conjugate ; Vaccination ; Neisseria meningitidis ; Polysaccharides ; Antibodies, Bacterial

Objective: To investigate the clinicopathologic and molecular genetic characteristics of myxoid pleomorphic liposarcoma (MPLPS). Methods: Six cases of MPLPS diagnosed and consulted in Fujian Provincial Hospital from 2015 to 2021 were collected for histomorphological observation, immunohistochemistry, and fluorescence in situ hybridization (FISH) detection of DDIT3 (CHOP) gene translocation and MDM2/CDK4 gene amplification. Results: There were four males and two females, aged 26-74 years (mean 53.8 years). The tumor size was 3.8-16.0 cm (mean 11.8 cm). All six cases had similar histopathologic features, showing overlapping histologic morphology of myxoid liposarcoma and pleomorphic liposarcoma. Four cases (4/6) were positive for S-100 protein, and the Ki-67 index was 50%-95%. All cases (6/6) were negative for DDIT3 (CHOP) translocation and MDM2/CDK4 amplification by FISH. TP53 (p.R248w) germline mutation was found in one case. Conclusions: MPLPS is a rare subtype of liposarcoma, characterized by overlapping morphology of myxoid liposarcoma and pleomorphic liposarcoma. Genetically, a few of them have TP53 gene germline mutations, but they lack of DDIT3 (CHOP) translocation or MDM2/CDK4 amplification.
Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Liposarcoma/pathology* ; Liposarcoma, Myxoid/diagnosis* ; Male ; Molecular Biology ; Proto-Oncogene Proteins c-mdm2/genetics* ; Translocation, Genetic

Objective: To explore the effect of P311 microspheres-loaded thermosensitive chitosan hydrogel on the wound healing of full-thickness skin defects in rats. Methods: The method of experimental study was adopted. The polyvinyl alcohol/sodium alginate microspheres (simple microspheres), P311 microspheres, and bovine serum albumin labeled with fluorescein isothiocyanate (FITC-BSA) microspheres were prepared by water-in-oil emulsification, and then their morphology was observed under a light microscope/inverted fluorescence microscope. Chitosan solution was prepared, chitosan solution and β-glycerol phosphate disodium hydrate were mixed to prepare simple thermosensitive hydrogels, and thermosensitive hydrogels loaded with simple microspheres or P311 microspheres were prepared by adding corresponding substances in simple thermosensitive hydrogels. The morphological changes of the prepared four liquids in the state of tilt was observed at 37 ℃. After being freeze-dried, the micromorphology of the prepared four liquids was observed under a scanning electron microscope. Eighteen 3-4-week-old male Sprague-Dawley rats were divided into normal group without any treatment, dressing group, chitosan group, hydrogel alone group, simple microspheres-loaded hydrogel group, and P311 microspheres-loaded hydrogel group, which were inflicted with one full-thickness skin defect wound on both sides of the back spine and were dealt correspondingly, with 3 rats in each group. Rats with full-thickness skin defects in the five groups were collected, the wound healing was observed on post injury day (PID) 0 (immediately), 5, 10, and 15, and the wound healing rates on PID 5, 10, and 15 were calculated. The wound and wound margin tissue of rats with full-thickness skin defects in the five groups on PID 15 and normal skin tissue in the same site of rats in normal group were collected, hematoxylin and eosin staining was conducted to observe the histological changes, immunohistochemical staining was performed to observe the expressions of CD31 and vascular endothelial growth factor (VEGF), and Western blotting was conducted to detect the protein expressions of CD31 and VEGF. The number of samples was all three. Data were statistically analyzed with one-way analysis of variance, analysis of variance for repeated measurement, and Bonferroni correction. Results: Simple microspheres were spherical, with loose and porous surface. The surfaces of P311 microspheres and FITC-BSA microspheres were smooth without pores, and the FITC-BSA microspheres emitted uniform green fluorescence. The diameters of the three microspheres were basically consistent, being 33.1 to 37.7 μm. Compared with chitosan solution and simple thermosensitive hydrogel, the structures of the two microspheres-loaded hydrogels were more stable in the state of tilt at 37 ℃. The two microspheres-loaded hydrogels had denser network structures than those of chitosan solution and simple thermosensitive hydrogel, and in the cross section of which microspheres with a diameter of about 30 μm could be seen. Within PID 15, the wounds of rats in the five groups were healed to different degrees, and the wound healing of rats in P311 microspheres-loaded hydrogel group was the best. On PID 5, 10, and 15, the wound healing rates of rats in dressing group and chitosan group were (26.6±2.4)%, (38.5±3.1)%, (50.9±1.5)%, (47.6±2.0)%, (58.5±3.6)%, and (66.7±4.1)%, respectively, which were significantly lower than (59.3±4.8)%, (87.6±3.2)%, (97.2±1.0)% in P311 microspheres-loaded hydrogel group (P<0.05 or P<0.01). The wound healing rates of rats in hydrogel alone group on PID 10 and 15, and in simple microspheres-loaded hydrogel group on PID 15 were (76.0±3.3)%, (84.5±3.6)%, and (88.0±2.6)%, respectively, which were significantly lower than those in P311 microspheres-loaded hydrogel group (P<0.05). The epidermis, hair follicles, and sebaceous glands could be seen in the normal skin of rats in normal group, without positive expressions of CD31 or VEGF. The wounds of rats in P311 microspheres-loaded hydrogel group on PID 15 were almost completely epithelialized, with more blood vessels, hair follicles, sebaceous glands, and positive expressions of CD31 and VEGF in the wounds than those of rats with full-thickness skin defects in the other four groups, and more protein expressions of CD31 and VEGF than those of rats in the other five groups. Conclusions: The P311 microspheres-loaded thermosensitive chitosan hydrogel can release the encapsulated drug slowly, prolong the drug action time, and promote wound healing in rats with full-thickness skin defects by promoting wound angiogenesis and re-epithelialization.
Rats ; Male ; Animals ; Hydrogels ; Vascular Endothelial Growth Factor A ; Chitosan/pharmacology* ; Serum Albumin, Bovine/pharmacology* ; Microspheres ; Polyvinyl Alcohol/pharmacology* ; Hematoxylin/pharmacology* ; Eosine Yellowish-(YS)/pharmacology* ; Rats, Sprague-Dawley ; Wound Healing ; Skin/injuries* ; Skin Abnormalities ; Soft Tissue Injuries ; Water/pharmacology* ; Alginates/pharmacology*

Background: and Purpose This study aimed to construct an optimal dynamic nomogram for predicting malignant brain edema (MBE) in acute ischemic stroke (AIS) patients after endovascular thrombectomy (ET). Methods: We enrolled AIS patients after ET from May 2017 to April 2021. MBE was defined as a midline shift of >5 mm at the septum pellucidum or pineal gland based on follow-up computed tomography within 5 days after ET. Multivariate logistic regression and LASSO (least absolute shrinkage and selection operator) regression were used to construct the nomogram. The area under the receiver operating characteristic curve (AUC) and decisioncurve analysis were used to compare our nomogram with two previous risk models for predicting brain edema after ET. Results: MBE developed in 72 (21.9%) of the 329 eligible patients. Our dynamic web-based nomogram (https://successful.shinyapps.io/DynNomapp/) consisted of five parameters: basal cistern effacement, postoperative National Institutes of Health Stroke Scale (NIHSS) score, brain atrophy, hypoattenuation area, and stroke etiology. The nomogram showed good discrimination ability, with a C-index (Harrell’s concordance index) of 0.925 (95% confidence interval=0.890–0.961), and good calibration (Hosmer-Lemeshow test, p=0.386). All variables had variance inflation factors of <1.5 and tolerances of >0.7, suggesting no significant collinearity among them. The AUC of our nomogram (0.925) was superior to those of Xiang-liang Chen and colleagues (0.843) and Ming-yang Du and colleagues (0.728). Conclusions Our web-based dynamic nomogram reliably predicted the risk of MBE in AIS patients after ET, and hence is worthy of further evaluation.