Objective: To analyze the association between intraoperative blood transfusion and adverse perinatal outcomes(a composite of maternal death, hepatic encephalopathy, etc) in patients with acute fatty liver of pregnancy (AFLP), identify independent risk factors for these outcomes, and develop and validate a risk prediction model for early identification of high-risk patients. Methods: Clinical data of 56 AFLP patients admitted to our hospital from January 2008 to January 2025 were retrospectively analyzed. The chi-square test was used to compare the incidence of adverse perinatal outcomes between the transfusion group and the non-transfusion group. Univariate and multivariate Firth-penalized logistic regression analyses were performed to identify independent predictors of adverse outcomes. Based on the identified independent risk factors, a combined prediction model was developed. Internal validation was performed using the Bootstrap method (1 000 resamplings) to assess the model′s generalizability. Model performance was evaluated using receiver operating characteristic(ROC) curves and calibration curves. Finally, a nomogram for predicting adverse perinatal outcomes in AFLP was constructed. Results: Overall, 57.1%(32/56) of the patients received blood product transfusion during the termination of pregnancy. Multivariate Firth-penalized logistic regression analysis showed that, given the limited sample size, intraoperative blood transfusion had no independent statistical effect on adverse outcomes (OR=0.812, 95%CI:0.133-3.698, P=0.797). Mediation analysis also revealed no significant indirect effect. The independent risk factors were decreased preoperative fibrinogen (OR=14.062, 95%CI:2.389-126.656, P=0.003), pregnancy with infection (OR= 4.536, 95%CI:1.143-22.107, P=0.031), and cesarean section (OR=8.691, 95%CI:1.321-90.081, P=0.023). The combined prediction model achieved an AUC of 0.881 (95% CI:0.793-0.969, P<0.001), indicating good discrimination. At the optimal cut-off value, the sensitivity was 65.6%, specificity 95.8%, positive predictive value 95.5%, and negative predictive value 67.6%. Internal validation by the Bootstrap method showed that the predictive model had good discrimination and no obvious overfitting. The calibration curve demonstrated that the model′s predicted risk was consistent with the actual observed risk. Based on this, an AFLP perinatal adverse outcome nomogram model was constructed. Conclusion: Under the limited sample size of this study, no independent statistical effect of intraoperative blood product infusion on adverse perinatal outcomes in AFLP patients was detected. A multivariate Firth-penalized logistic regression model incorporating decreased preoperative fibrinogen, pregnancy with infection, and cesarean delivery demonstrated good discrimination and calibration. The derived nomogram may serve as an exploratory tool for early risk stratification and proactive intervention.

Cognitive impairment is one of the most common non-motor symptoms of Parkinson′s disease, which seriously affects the health and quality of life of patients. Therefore, it is particularly important to identify and predict the future cognitive decline of this population. Cognitive reserve can compensate for brain damage caused by aging and brain diseases, and reduce and delay cognitive decline, reflecting the different sensitivity of individuals to cognitive impairment. However, the specific relationship between the two is not fully understood. This paper mainly analyzes the concept, measurement method, genetics and functional imaging of cognitive reserve in Parkinson′s disease to further reveal the relationship between cognitive impairment and cognitive reserve in Parkinson′s disease.

Cognitive impairment is one of the most common non-motor symptoms of Parkinson′s disease, which seriously affects the health and quality of life of patients. Therefore, it is particularly important to identify and predict the future cognitive decline of this population. Cognitive reserve can compensate for brain damage caused by aging and brain diseases, and reduce and delay cognitive decline, reflecting the different sensitivity of individuals to cognitive impairment. However, the specific relationship between the two is not fully understood. This paper mainly analyzes the concept, measurement method, genetics and functional imaging of cognitive reserve in Parkinson′s disease to further reveal the relationship between cognitive impairment and cognitive reserve in Parkinson′s disease.

Ceftazidime-avibactam （CAZ/AVI）is a novel β-lactam antibiotic with broad-spectrum antibacterial activity and good tolerability. However， the physiological and pathological differences in special populations [e.g. augmented renal clearance （ARC） patients， undergoing continuous renal replacement therapy （CRRT） patients， neonates and children， obese patients， undergoing extracorporeal membrane oxygenation （ECMO） patients， elderly patients and liver dysfunction patients] may affect the pharmacokinetic （PK） properties of CAZ/AVI， leading to treatment failure. At present， there is currently a lack of corresponding guidelines or consensus on dose adjustment of CAZ/AVI in special populations. This article summarizes the research on PK/ pharmacodynamic （PD） characteristics and dose adjustment of CAZ/AVI in special populations and recommends the following dosing regimens： for ARC patients， the recommended dose is 2.5 g， q8 h； for undergoing CRRT patients with infections caused by sensitive strains （i.e. MIC＜4 mg/L） and infections at sites where hydrophilic antibiotics distribute well， a dose of 1.25 g， q8 h may be used； for undergoing CRRT patients with less sensitive strains or sites with poorer drug distribution， a dose of 2.5 g， q8 h or continuous infusion may be considered； for children aged 6 months to ＜18 years with normal or mildly impaired renal function， a dose of 62.5 mg/kg， q8 h is infused for 2 h （maximum dose not exceeding 2.5 g per dose）； for infants aged 3～6 months with normal or mildly impaired renal function， a dose of 50 mg/kg， q8 h is infused for 2 h； for obese patients， the recommended dose is 2.5 g， q8 h， with therapeutic drug monitoring recommended；undergoing ECMO patients， elderly patients， and those with impaired liver function may also use the recommended dose of 179368757@qq.com 2.5 g， q8 h.

Gait deficits and balance disturbances are prevalent clinical features in Parkinson′s disease (PD). There is an increasing body of evidence pointing towards the degeneration of central cholinergic neurons as a crucial factor leading to these disturbances in PD. This paper presents a comprehensive review of the relevant research on the involvement of the central cholinergic system in the mechanisms underlying gait deficits and balance disturbance in PD. The aim is to provide new perspectives and insights for the treatment of gait deficits and balance disturbances in PD.

Objective To explore the effect and mechanism of hesperidin in treating the lung injury in the mouse model of respiratory syncytial virus (RSV)-induced bronchiolitis. Methods A mouse model of RSV-induced bronchiolitis was established,and 60 BALB/c mice were assigned into a control group,a model group,a low-dose hesperidin (18 mg/kg) group,a high-dose hesperidin (36 mg/kg) group,and a high-dose hesperidin (36 mg/kg)+Jagged1(1 mg/kg) group by random number table method,with 12 mice in each group. Corresponding doses of drugs were administrated for intervention,and the control group and model group were administrated with the same amount of saline.The bronchoalveolar lavage fluid (BALF) samples were collected and alveolar macrophages were isolated.ELISA was employed to detect the levels of interleukin (IL)-4,IL-6,tumor necrosis factor-α (TNF-α),and IL-10 in BALF,and flow cytometry to detect the M1/M2 polarization of macrophages.qRT-PCR and Western blotting were respectively conducted to detect the mRNA and protein levels of inducible nitric oxide synthase (iNOS),arginase 1 (Arg-1),Jagged1,and Notch1 in the lung tissue. Results Compared with the control group,the modeling of RSV-induced bronchiolitis elevated the IL-4,IL-6,and TNF-α levels,increased the proportion of M1-type macrophages and the lung inflammation and mucus secretion scores,and up-regulated the mRNA and protein levels of iNOS,Jagged1,and Notch1 in BALF (all P<0.001).Meanwhile,the modeling lowered the IL-10 level,decreased the proportion of M2-type macrophages,and down-regulated the mRNA and protein levels of Arg-1 (all P<0.001).Compared with the model group,low- and high-dose hesperidin lowered the IL-4,IL-6,TNF-α levels,decreased the proportion of M1-type macrophages and the lung inflammation and mucus secretion scores,and down-regulated the mRNA and protein levels of iNOS,Jagged1,and Notch1 in BALF (all P<0.05).Moreover,hesperidin elevated the IL-10 level,increased the proportion of M2-type macrophages,and up-regulated the mRNA and protein levels of Arg-1 (all P<0.001).Using recombinant Jagged1 protein to activate Notch1 signaling pathway can significantly attenuate the promotion of high-dose hesperidin on M2 macrophage polarization and amelioration of lung inflammation damage (all P<0.01). Conclusion Hesperidin may alleviate the lung inflammation damage in mice with RSV-induced bronchiolitis by inhibiting the Jagged1/Notch1 signaling pathway and promoting the M2-type polarization of macrophages.
Animals ; Mice ; Bronchiolitis/metabolism* ; Hesperidin/metabolism* ; Interleukin-10/pharmacology* ; Interleukin-4/pharmacology* ; Interleukin-6/metabolism* ; Jagged-1 Protein/pharmacology* ; Lung Injury/metabolism* ; Macrophages ; Mice, Inbred BALB C ; RNA, Messenger/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

Objectives:To investigate the genetic characteristics of the blaNDM-1-carrying plasmid of the multidrug resistant Enterobacter hormaechei subsp. hoffmannii clinical isolate C37, and constructing a phylogenetic tree of the 66 publicly available genomes of the Enterobacter hormaechei subsp. hoffmannii to explore its global epidemic situation. Methods:Carbapenem-resistant Enterobacter cloacae complex (CRECC) strains isolated from the First Affiliated Hospital of Sun Yat-sen University from August 2014 to August 2021 were collected. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) and 16S rDNA Sanger sequencing were used for species identification. Micro broth dilution method was used for antibacterial susceptibility test. The polymerase chain reaction (PCR) was used to detect the β-lactamase resistance gene and plasmid-mediated quinolone resistance (PMQR) gene carried by the C37 strain. The conjugation experiment was used to confirm the conjugative metastasis of the resistance genes in C37 strain. Whole genome of the C37 strain was sequenced. Core genome was extracted and the phylogenetic analysis of 66 publicly available Enterobacter hormaechei subsp. hoffmannii was performed. Results:Enterobacter hormaechei subsp. hoffmannii C37 strain is resistant to third-generation cephalosporins, carbapenems, aminoglycosides and quinolones, and carries blaACT-5, blaNDM-1, qnrA1, aac(6′)-Ib-cr, oqxAB, fosA, dfrA15 and other resistance genes, as well as IncX3, IncX4, IncFIB and IncFII plasmids. Multilocus sequence typing (MLST) analysis showed that C37 strain belongs to the ST78 type of Enterobacter cloacae complex (ECC). Conclusions:ST78 type Enterobacter hormaechei subsp. hoffmannii is closely related to the spread of carbapenem resistance genes. It is a potential high-risk clone to spread carbapenem resistance genes. The prevalence and trends of ST78 type Enterobacter hormaechei subsp. Hoffmannii should be monitored.

Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance, preventing autoimmune responses, and minimizing tissue damage by regulating the duration and intensity of the immune response. Furthermore, immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor response. Based on substantial physiological analyses as well as preclinical and clinical studies, checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of cancers. In the last few years, extensive evidence has supported the immunoregulatory effects of traditional Chinese medicines (TCMs). The main advantage of TCMs and natural medicine is that they usually contain multiple active components, which can act on multiple targets at the same time, resulting in additive or synergistic effects. The strong immune regulation function of traditional Chinese medicine on immune checkpoints has also been of great interest. For example,

In order to deal with the increasing number of multidrug resistant Enterobacteriaceae , polymyxins were re-introduced into clinical practice .The resistance of polymyxins had gained global attention.In addition to chromosomal mediated drug resistance , a new plasmid-mediated colistin-resistance gene mcr-1 made transferation of polymyxins resistance more easily .Here, the mechanisms of chromosome mediated polymyxin resistance and plasmide-mediated drug resistance , including the distribution , prevalence, transfer mechanism, and genetic environments of mcr-1, current methods for polymyxins susceptibility testing methods and novel qualitative detection techniques were reviewed to provide information to cope with the growing problem of bacterial drug resistance .

BACKGROUND:Herba epimedi, a traditional Chinese medicine, has a long time in dealing with various orthopedic disorders. Icarinwithmany biological activites is one of the most important compositions of Herba epimedi. OBJECTIVE:Toinvestigate the effects of icarin on osteogenic differentiation of mesenchymal stem cels and the underlying mechanisms. METHODS:Bone marrow mesenchymal stem cels were treated using icarin with or without osteogenic mediumin vitro. Osteogenic differentiation markers, including runt-related transcription factor 2, osteocalcin and osterix, were detected by real time-qPCR. Alizarin red staining was used to measure calcium nodes generated by osteoblasts induced frombonemarrow mesenchymal stem cels. The proximal tibia bone structure of rats fed with icarin (2 mgperday) for 5 weeks was detected and analyzed by MicroCT. RESULTS AND CONCLUSION:Icarin was able to promote the expression of genes related to osteogenic differentiation in the absence or presence of osteogenic induction. Icarin could obviously increase the quantity of calcium nodes whenmesenchymal stem celswere cultured in the osteogenic medium. The animal experiment showed that icarin improved formation of trabecular bone.