Purpose To observe the effect of Necrostatin-1 (Nec-1),a necroptosis inhibitor,on the inflammation in unilateral ureter obstruction mice.Methods Male C57BL/6J mice were randomly divided into sham operation group,unilateral ureter obstruction operation group and UUO + Nec-1 treatment group,and the mice were sacrificed at 7th day after operated.Scr and BUN were measured.The pathological changes in the kidney were observed by HE staining.Immunohistochemistry and Western blot were used to detect the protein expression of necroptosis-related indicators RIP1,RIP3,MLKL and inflammatory cytokines TNF-α,IL-1β and MCP-1.Results Compared with sham operation group,the expression of RIP1,RIP3 and MLKL protein increased in the renal tissue of UUO mice,accompanied with increased expression of TNF-α,IL-1β and MCP-1.Nec-1 treatment significantly decreased above-mentioned protein expression in UUO mice,and also reduced renal interstitial inflammation and renal tubal injury according to HE staining.Scr and BUN levels suggested improved renal function.Conclusion Nec-1 could relieve the inflammatory reaction in renal tissue of the UUO mice by inhibiting necroptosis,which may be a new target for the treatment of secondary inflammation.

BACKGROUNDTreating intramedullary spinal cord gliomas is a big challenge because of limited options, high recurrence rate and poor prognosis. An intramedullary glioma model is prerequisite for testing new treatments. This paper describes the establishment of a rodent intramedullary glioma model and presents functional progression, neuroimaging and histopathological characterization of the tumour model.

METHODSFischer344 rats (n = 24) were randomized into two groups. Group 1 (n = 16) received a 5 µl intramedullary implantation of 9L gliosarcomal (10⁵) cells. Group 2 (n = 8) received a 5 µl intramedullary injection of Dulbecco's modified Eagle medium. The rats were anesthetized, the spinous process of the T₁₀ vertebra and the ligamentum flavum were removed to expose the T₁₀₋₁₁ intervertebral space and an intramedullary injection was conducted into the spinal cord. The rats were evaluated preoperatively and daily postoperatively for neurological deficits using the Basso, Beattie and Bresnahan scale. High resolution magnetic resonance images were acquired preoperatively and weekly postoperatively. When score equal to 0, rats were sacrificed for histopathological examination.

RESULTSRats implanted with 9L gliosarcoma cells had a statistically significant median onset of hind limb paraplegia at (16.0 ± 0.4) days, compared with rats in the control group in which neurological deficits were absent. Imaging and pathological cross sections confirmed intramedullary 9L gliosarcoma invading the spinal cord. Rats in the control group showed no significant functional, radiological or histopathological findings of tumour.

CONCLUSIONSRats implanted with 9L cells regularly develop paraplegia in a reliable and reproducible manner. The progression of neurological deficits, neuroimaging and histopathological characteristics of intramedullary spinal cord gliomas in rats is comparable with the behaviour of infiltrative intramedullary spinal cord gliomas in patients.

Animals ; Cell Line, Tumor ; Disease Models, Animal ; Glioma ; pathology ; Male ; Rats ; Rats, Inbred F344 ; Spinal Cord Neoplasms ; pathology

OBJECTIVE: To identify pathogenic variants in two patients with suspected for Mowat-Wilson syndrome (MWS). METHODS: Genomic DNA was extracted from peripheral blood samples of the patients and his family members, and gene variants were analysis by Trio-whole exome sequences and copy number variation sequencing. RESULTS: Patient 1 was found to carried a de novo heterozygous c.2769C>A (p.Y923*) nonsense variant of ZEB2 gene. The variant was not found in his healthy parents and sister. Patient 2 carried a de novo heterozygous frameshift variant of the ZEB2 gene, namely c.315delC (p.A105Afs*3), which has not been previously reported. Both variants were predicted to be pathogenic and can lead to premature occurrence of stop codons. CONCLUSION The heterozygous c.2769C>A (p.Y923*) and c.315delC (p.A105Afs*3) variants of the ZEB2 gene probably underlay the pathogenesis in the two patients. Gene testing has facilitated confirmation of the diagnosis and genetic counselling.
DNA Copy Number Variations ; Facies ; Hirschsprung Disease ; Humans ; Intellectual Disability/genetics* ; Microcephaly/genetics* ; Zinc Finger E-box Binding Homeobox 2/genetics*

Purpose To investigate the effect of grape seed proanthocyanidins on the phenotype-transforming marker protein expression of db/db renal cells in mice model of type 2 diabetes,and to explore the protective mechanism of grape seed extract on diabetic renal injury in db/db mice.Methods Male db/db diabetic mice were randomly divided into two groups:diabetic group (db/db group) and diabetic + grape seed proanthocyanidin extract group (db/db + GSPE).The same week-old male db/m mice was used as normal controls (db/m) and grape seed proanthocyanidin extract gavage treatment group (db/m +grape seed proanthocyanidin extract group,db/m + GSPE).The mice of db/db + GSPE group and db/m + GSPE group were administered daily with grape seed proanthocyanidin extract (5mg/kg) by gavage.Results Renal tissues of db/db diabetic mice showed increased expression of α-SMA,p-p38MAPK,pERK1/2 and 8-OHdG level,and down-regulation in E-cadherin expression compared with db/m group (P ＜ 0.05).However,the alternations of α-SMA,p-p38,p-ERK1/2,E-cadherin protein levels,and 8-OHdG level,in db/db group were reversed by addition of grape seed proanthocyanidin extract (P ＜ 0.05).Conclusion Grape seed proanthocyanidin extract inhibits the epithelial to mesenchymal transition (EMT) associated protein,by decreasing ROS production,and activating p38 MAPK and ERK1/2.These findings suggest that grape seed proanthocyanidin extract provides a treatment option for diabetic nephropathy.

OBJECTIVETo observe the clinical efficacy and mechanism of Zhuyu Tongfu (ZYTF) Serial Recipe combined with acupuncture and massotherapy in treating hypertensive cerebral hemorrhage (HCH).

METHODSOne hundred and eighteen patients with hypertensive cerebral hemorrhage, on the basis of conventional Western medicine treatment, were randomly divided into ZYTF combined with acupuncture and massotherapy group (treated group) and simple Western medicine group (control group); the clinical efficacy, neurofunction deficit scoring (NDS) alterations and hematoma absorption rate of both groups were observed, and also the plasma superoxide dismutase (SOD) activity, plasma lipid peroxidase (LPO) content, erythrocyte glutathion peroxidase (GSH-Px) activity, hematocrit (Ht) and the whole blood viscosity (Va) change were also observed.

RESULTSIn the treated group, the clinical efficacy, NDS improvement and hematoma absorption rate were superior to that of the control group; comparison between the two groups after treatment showed that plasma SOD activity and GSH-Px activity got more elevated and plasma LPO content, Ht and Va more lowered in the the treated group than those in the control group.

CONCLUSIONZYTF combined with acupuncture and massotherapy has better effect, its therapeutic mechanism was possibly correlated to the elevation of plasma SOD activity, GSH-Px activity and lowering of plasma LPO content, Ht and Va.

Acupuncture Therapy ; methods ; Adult ; Aged ; Aged, 80 and over ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Intracranial Hemorrhage, Hypertensive ; therapy ; Male ; Massage ; methods ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Treatment Outcome

Dental caries are the most prevalent chronic infections in the oral cavity,and Streptococcus mutans acts as the main cariogenic bacterial species. Antibacterial quaternary ammonium compounds (QAs) have been developed to preveFnt or treat dental caries. However, there is no report on the tolerance of S.mutans to QAs.In this study, we investigated the development of S. mutans persistence induced by a novel dental caries defensive agent, dimethylaminododecyl methacrylate (DMADDM), for the first time. Typical biphasic killing kinetics for persisters were observed in both S. mutans planktonic and biofilm cultures challenged by DMADDM at concentrations of 20 and 200 μg·mL-1,respectively. The persisters tolerated six other antibiotics with different antibacterial mechanisms, while only daptomycin and vancomycin could slightly reduce the persister numbers in planktonic cultures. The distribution of persisters in DMADDM-treated biofilms was similar to that in the untreated control, except that the total biomass and biofilm height were significantly reduced.A higher exopolysaccharides (EPS):bacteria ratio was observed in DMADDM-treated biofilms. Persisters in biofilms significantly upregulated gtf gene expression, indicating an increase in the bacteria's ability to produce EPS and an elevated capability of cariogenic virulence. Carbon source metabolism was significantly reduced,as related metabolic genes were all downregulated in persisters. Concentrations of 0.1 mM, 1 mM and 10 mM of extra glucose significantly reduced the number of persisters both in planktonic and biofilm conditions. The formation of non-inheritable and multidrug tolerant persisters induced by DMADDM suggested that drug tolerance and new persistent eradication strategies should be considered for oral antibacterial agents.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

OBJECTIVETo investigate the relationship between inflammatory factors and two Chinese medicine (CM) syndrome types of qi stagnation and blood stasis (QSBS) and qi deficiency and blood stasis (QDBS) in patients with acute coronary syndrome (ACS).

METHODSSixty subjects with ACS, whose pathogenesis changes belongs to qi disturbance blood stasis syndrome, were divided into 2 groups: 30 in the QSBS group and 30 in the QDBS group. The comparative analysis on them was carried out through comparing general information, coronary angiography and inflammatory factors including intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40) and lipoprotein-associated phospholipase A2 (Lp-PLA2).

RESULTSCompared with the QSBS group, Lp-PLA2 and YKL-40 levels in the QDBS group showed no-significant difference (P>0.05); ICAM-1 was significantly higher in the QDBS group than in the QSBS group in the pathological processes of qi disturbance and blood stasis syndrome of ACS (P<0.05).

CONCLUSIONSInflammatory factor ICAM-1 may be an objective basis for syndrome typing of QSBS and QDBS, which provides a research direction for standardization research of CM syndrome types.