Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

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.

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ²=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ²=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.
Cardiopulmonary Resuscitation ; Child ; Child, Preschool ; Female ; Heart Arrest/therapy* ; Heart Defects, Congenital/therapy* ; Humans ; Intensive Care Units, Pediatric ; Male ; Retrospective Studies

OBJECTIVE: To investigate the therapeutic effect of spleen low molecular weight extracts on epileptics hydrochloride-induced leukopenia in mice and explore its mechanism. METHODS: The model of leukopenia in mice was established by the injection of epirubicin hydrochloride (10 mg/kg). After the injection of chemotherapeutic drugs, leukocytopenia mice were treated with different doses of spleen low molecular weight extract, Ganoderma oral solution and recombinant granulocyte colony stimulating factor (rhG-CSF). The general survival status indicators such as body weight, coat color and athletic ability of mice in each group were recorded; the tail vein blood of mice in each group was collected and the white blood cell count in them was calculated; bone marrow of mice was taken and bone marrow smears were observed. RESULTS: In the model group, the weight of the mice gradually decreased in the later period, their coat became dark and rough, and the ability to exercise decreased, while the mice in the treatment groups showed different degrees of improvement in their survival status except for the mice treated by rhG-CSF. There was no significant fluctuation in the white blood cell count of the blank control mice. After injection of epirubicin, the white blood cell count of peripheral blood in the model mice and treated mice were decreased. The white blood cell count was lower in the mice treated with high-dose low molecular weight extract and rhG-CSF than that in other experimental groups. Bone marrow smear showed that the proportion of bone marrow nucleated cells in the mice treated with the low molecular weight extract of the spleen was significantly higher than that of model mice (P<0.05). CONCLUSION The low molecular weight spleen extracts can significantly improve the hematopoietic state of mouse bone marrow, promote the proliferation of inhibited bone marrow cells, and thus has the effect of treating leukopenia in mice.
Animals ; Epirubicin ; Granulocyte Colony-Stimulating Factor ; Leukocyte Count ; Leukopenia/drug therapy* ; Mice ; Molecular Weight ; Plant Extracts ; Recombinant Proteins ; Spleen

[Abstract] Objective: To explore the key genes and molecular mechanisms of liver metastasis in colorectal cancer (CRC), and to provide potential targets and biomarkers for the treatment of CRC with liver metastasis. Methods: Based on the bioinformatics method, the gene data sets of CRC liver metastasis were downloaded from the GEO database to screen the differentially expressed genes (DEGs); the GO and KEGG enrichment analyses of DEGs were performed by using DAVID online tool, and the protein-protein interaction (PPI) network was constructed to screen out the key genes, and subsequently the prognosis was analyzed. Results: A total of 321 DEGs were selected from 183 CRC specimens and 39 liver metastasis specimens, including 153 up-regulated genes and 168 downregulated genes. The results of enrichment analysis of GO and KEGG showed that the functions of DEGs were mainly related to protein activation cascade, inflammatory response, extracellular matrix, platelet degranulation, complement and coagulation cascade reaction etc. 8 key CRC genes (ALB, APOB, FGA, F2, APOA1, SERPINC1, FGG and AHSG) were screened by PPI network. Survival analysis showed that patients with high expressions of SERPINC1 and FGG had poor prognosis(all P<0.05). Conclusion: The biological functions and signaling pathways of DEGs are related to the occurrence and development of liver metastasis. The 8 key genes may be the potential therapeutic targets of CRC liver metastasis, and SERPINC1 and FGG may be new prognostic markers.

Objective To investigate serum lipid profiles in newly diagnosed patients with polycystic ovary syndrome (PCOS) using lipidomics and correlate these features with hyperinsulinemia and hyperandrogenism associated with PCOS and obesity. Methods 32 newly-diagnosed PCOS women and 34 controls were enrolled and divided into obese and lean subgroups according to the body mass index (BMI). Anthropometric, biochemical, and hormonal parameters were collected. Serum lipid profiles including phospholipids, free fatty acids (FFAs), and bioactive lipids were analyzed using GC-MS and LC-MS. Results PCOS patients, in particular, the obese ones with fatty liver, have abnormal phosphatidylcholine (PC)/lysophospholipid (LPC) metabolism. PC was increased (16∶0, 18∶0, 18∶1, 18∶2, and 20∶4), while LPC was decreased (16∶0, 18∶0, and 18∶1; all P<0.05). Serum polyunsaturated fatty acids (PUFAs), were decreased significantly, and the long chain saturated fatty acid was increased. We also found that insulin stimulated the metabolism of PUFAs, but the androgen inhibits the metabolism of PUFAs by measuring their metabolites. Conclusion PCOS patients have metabolic disorders of phospholipids and PUFAs. Insulin stimulated while androgen inhibited PUFAs metabolism.

Objective To investigate the effects of intravitreous injection of conbercept for macular edema secondary to retinalvein occlusion(RVO) during 6 months period.Methods A retrospective clinical study.34 patients (34 eyes) were included in this study,who were diagnosed with macular edema due to retinal vein occlusion by ophthalmologic examination,fundus photography,optical coherence tomography (OCT),fundus fluorescein angiography and other methods.The best corrected visual acuity (BCVA) was examined using the international standard visual acuity chart,and the results were converted to the logMAR visual acuity.The average logMAR BCVA was 0.90 ± 0.68,and the mean macular central retinal thickness (CMT) was (672.27±227.51) μm before treatment.All subjects received intravitreal injection of 0.5 mg conbercept (0.05 ml) at the first visit.Injections were repeated based on the visual acuity changes and the OCT findings.34 eyes received 69 times of injection,the average number of injections was 2.03 ± 1.03.BCVA,OCT were examined before and after treatment using the same method.BCVA and CMT changes,drugs and treatments associated cardiac and cerebral vascular accident,intraocular pressure elevation,retinal tears,retinal detachment,endophthalmitis and other complications after treatment were observed.Linear correlation analysis was used to analyze the correlation between prognosis BCVA and baseline BCVA,correlation between prognosis BCVA and baseline CMT,and also correlation between BCVA and CMT at different time points before and after treatment.Results At 1 week and 1,2,3,6 months after treatment,the average logMAR BCVA was 0.65±0.61,0.56±0.61,0.46±0.55,0.56±0.71,0.44±0.48 respectively.During 1,2,3,6 months after treatment,the mean logMAR BCVA were improved with statistically significant difference (Z=34.029,47.294,41.338,43.603;P＜0.05),while 1 week after treatment showed no obvious improvement (Z=21.941,P＞0.05).At 1 week and 1,2,3,6 months after treatment,the average CMT was (285.89 ± 96.69),(256.65 ± 143.39),(278.68 ± 156.92),(290.11 ± 188.17),(217.15 ± 48.04) μm respectively.At 1 week and 1,2,3,6 months after treatment,the mean CMT were all decreased with statistically significant difference (Z=68.500,98.735,93.235,91.132,109.162;P＜0.05).There was a positive correlation between the prognosis visual acuity and preoperative visual acuity (r=0.682,P＜0.05).However,there was no correlation between the prognosis vision and the degree of macular edema before treatment (r=0.078,P＞0.05).Before and 3,6 months after treatment,BCVA was negatively correlated with CMT (r=0.491,0.416,0.386;P＜0.05),while there was no correlation in other time points (r =0.145,0.217,0.177;P＞ 0.05).Systemic adverse reactions and persistent intraocular pressure elevation,iatrogenic cataract,retinal detachment,retinal tear,endophthalmitis and ocular complications were never found in the follow-up period.Conclusion Intravitreal conbercept is a safe and effective approach for RVO,which can significantly improve visual acuity and reduce CMT.

To prepare tanshinone ⅡA loaded nanostructured lipid carrier (Tan ⅡA-NLC), and study its in vitro transdermal permeation characteristics. The Tan ⅡA-NLC was prepared by high pressure homogenization technology and optimized by Box-Behnken design-response surface method, and it was characterized in terms of morphology, particle size, zeta potention, et al. The transdermal permeation of Tan ⅡA-NLC was evaluated by using Franz diffusion cells. The results showed that, the optimal formulation was as follows: drug/lipid materials ratio 88, GMS/MCT ratio 2, emulsifier concentration 1%, average particle size (182±14) nm, polydispersity index PDI (0.190 6±0.024 5), zeta potential (－27.8± 5.4) mV, encapsulation efficiency EE (86.44%±9.26%) and drug loading DL (0.98%±0.18%), respectively. The in vitro transdermal permeation results showed that as compared with Tan ⅡA solution, Tan ⅡA-NLC had lower transdermal permeation amount after applying drug for 24 h, but its retention in the epidermis was 3.18 times that of solution. These results indicated that the prepared Tan ⅡA-NLC could effectively increase the regention of Tan ⅡA in the epidermis, and had a broad application prospect.

OBJECTIVETo evaluate the protective effect of S-isopentenyl-L-cysteine,a new cysteine derivative,on DNA damage induced by radiation by using acute radiation injury animal models.

METHODSForty ICR mice were randomly divided into five groups:the control group,1.0Gy gamma irradiation group,1.0Gy gamma irradiation combined with S-isopentenyl-L-cysteine group,7.2Gy gamma irradiation group,and 7.2Gy gamma irradiation combined with S-isopentenyl-L-cysteine group,with 8 mice in each group.The comet assay and bone marrow polychromatic micronucleus experiments were performed to evaluate the double-strand DNA breaks in ICR mice exposed to 1.0 and 7.2Gy gamma-ray, respectively.

RESULTSThe tail DNA percentage,tail length,tail moment,and olive tail moment of peripheral blood lymphocytes in 7.2Gy gamma irradiation group were significantly higher than that of the control group (P<0.01).And it was also observed that above experimental indexes of 7.2Gy gamma irradiation combined with S-isopentenyl-L-cysteine group was significantly less than that of 7.2Gy gamma irradiation group (P<0.05). In addition,the micronucleus rate of 1.0Gy gamma irradiation group and 7.2Gy gamma irradiation group were both significantly higher than in the control group (P<0.01). In addition,in mice given S-isopentenyl-L-cysteine before irradiation,the micronucleus rate of ICR mice exposed to 1.0 and 7.2Gy gamma-ray decreased from (39.5000 ± 3.3141)‰ to (28.1667±4.1345)‰ (P=0.033) and from (76.5000 ± 4.6242)‰ to (22.8333 ± 3.6553)‰(P=0.000),respectively. The bone marrow polychromatic micronucleus experiment indicated that the value of polychromatic erythrocyte (PCE)/normochromatic erythrocyte(NCE) of ICR mice exposed to 1.0 and 7.2Gy gamma-ray was less than the control group(P<0.05). Meanwhile,after irradiating by certain dose,the value of PCE/NCE in mice given S-isopentenyl-L-cysteine before irradiation was significantly higher than the corresponding groups (P<0.05).

CONCLUSIONS-isopentenyl-L-cysteine has a good protective effect against DNA damage induced by radiation.

Animals ; Bone Marrow ; Cysteine ; DNA Damage ; Disease Models, Animal ; Gamma Rays ; Mice ; Mice, Inbred ICR ; Radiation Injuries ; Radiation-Protective Agents