Reactive astrocytes, which exhibit a correlation with the degeneration of dopaminergic neurons, are present in a considerable number during the progression of Parkinson's disease (PD). However, the underlying factors shaping astrocyte reactivity and neuroinflammation in PD remain inadequately elucidated. Here, we demonstrate that fibroblast growth factor 7 (FGF7)/FGF receptor 2 (FGFR2) autocrine signaling intensifies astrocyte reactivity and inflammation. Genetic deletion of Arrb2, β-Arrestin2 encoding gene, led to escalated astrocyte reactivity in MPTP-treated mice, which was further substantiated in astrocyte-specific Arrb2 knockdown mice. RNA sequencing profiling of Arrb2 knockout astrocytes identified Fgf7 as a critical effector of astrocyte reactivity. Subsequently, conditional knockdown of Fgf7 and its receptor Fgfr2 in astrocytes elicited advantageous effects for MPTP-treated mice by restraining the inflammatory phenotypic transition of reactive astrocytes. Furthermore, deletion of astrocytic Fgf7 mitigated MPTP-induced pathology in Arrb2 knockout mice. Mechanistically, STAT1 was distinguished as the transcription factor suppressing Fgf7 expression, while β-Arrestin2 counteracted the proteasomal degradation of STAT1 by binding to RNF220, an E3 ubiquitin ligase for STAT1. More importantly, selectively engaging dopamine D2 receptor (Drd2)/β-Arrestin2-biased signaling using the agonist UNC9995 exhibited therapeutic potential in MPTP-treated mice via moderation of astrocytic FGF7 production, thereby restoring balance in astrocyte reactivity. Collectively, our study bridges a crucial knowledge gap by elucidating the novel functions of FGF family members within the central nervous system, particularly within the context of PD. The autocrine signaling of FGF7/FGFR2 represents a novel mechanism and a potential druggable target for modulating astrocyte-derived inflammation.

Objective:To report the clinical manifestations, structural and functional imaging features of 3 patients with progressive supranuclear palsy with predominant cerebellar ataxia (PSP-C) assisted by florzolotau ( 18F) positron emission tomography (tau PET) imaging, and conduct a literature review, aiming to provide a basis for the diagnosis and treatment of this rare type of PSP. Methods:The clinical data, brain magnetic resonance imaging, 18F-fluorodeoxyglucose PET ( 18F-FDG PET) and tau PET head imaging features of 3 patients with PSP-C who were admitted to the Department of Neurology, Peking Union Medical College Hospital from January 2019 to December 2021 were summarized, and a systematic review of related case reports or series studies from China and abroad was conducted. Results:The age of onset of the 3 patients was 55-61 years, and the disease duration was 2-5 years at the time of diagnosis. All patients had an onset of instable walking and had repeated falls, and the duration between fall and disease onset was 0.5-3.0 years, with an average of 1.5 years. At the time of diagnosis, all patients showed gait ataxia with or without limb ataxia. The results of the brain magnetic resonance imaging showed that all patients had midbrain atrophy and midbrain-to-pons ratio<0.52. The tau PET results of all patients showed significant tau protein deposition in the midbrain and mild to moderate tau protein deposition in the cerebellum, and case 2 had concomitant mild tau protein deposition in the prefrontal lobe and decreased 18F-FDG PET metabolism in this region, supporting the diagnosis of PSP. Literature review showed that 24 patients with PSP complicated with cerebellar ataxia were reported, and 23 patients provided detailed clinical data. All patients had gait ataxia on physical examination and the clinical manifestations were consistent with those of this group. Conclusions:PSP-C is characterized by early gait ataxia and falls as the core manifestations. Structural imaging shows mesencephalic atrophy, and tau PET shows mesencephalic and cerebellar uptake. In the case of atypical PSP, head magnetic resonance imaging combined with tau PET imaging is helpful to further determine the diagnosis of PSP.

Presynaptic dopaminergic PET imaging is a useful method for the diagnosis of parkinsonism. Based on the expert consensus on operation and clinical application of dopamine transporter brain PET imaging technology published in 2020, this paper further recommends the relevant elements of result interpretation of presynaptic dopaminergic PET imaging.

Objective:To investigate the protective function and mechanism of β-hydroxybutyrate (β-HOB) on cisplatin (CP)-induced nephrotoxicity.Methods:C57BL/6 male mice aged 10 weeks were randomly divided into the following three groups: control group (no special treatment), β- HOB+CP group (mice received intraperitoneal injection of 20 mmol/kg β-HOB for 10 days), CP group (received intraperitoneal injection of normal saline for 10 days). CP group and β-HOB+CP group were given once cisplatin (20 mg/kg) intraperitoneal injection on the 8th day in the experiment. On the 10th day, all the mice were sacrificed. Renal pathology was evaluated by HE staining; blood samples were collected for blood urea nitrogen (BUN) and serum creatinine (Scr) measurement; immunohistochemistry staining was performed to detect the protein level of Caspase3, Cleaved-caspase3, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) in renal tissues; Western blotting was used to detect the relative expression levels of p-MAPK/MAPK and p-NF-κB/NF-κB. In vitro experiment, HK-2 cells were set into three groups: control group, CP group, β-HOB+CP group, and β-HOB+CP+Sappanone A (Sap, MAPK-p38 activator) group. The expression levels of p-MAPK, p-NF-κB, Caspase3 and Cleaved-caspase3 were tested by cell immunofluorescence. The cell apoptosis and mitochondrial membrane potential (MMP) were examined by flow cytometry. DNA damage was detected by TUNEL staining. Results:In vivo experiments, the renal pathological injury score, BUN and Scr in CP group were significantly higher than those in control group (all P<0.05), while renal pathological injury score, BUN and Scr in β-HOB+CP group were lower than those in CP group (all P<0.05). The protein expression levels of p-MAPK, p-NF-κB, Caspase3 and Cleaved-caspase3 in CP group were higher than those in control group, while these indexes in β-HOB+CP group were lower than those in CP group (all P<0.05). In vitro experiments, compared with CP group, the MMP was higher in β-HOB+CP group; the ratio of cell apoptosis, the expression of Caspase3, Cleaved-caspase3, p-MAPK and p-NF-κB, and the number of TUNEL staining positive cells were significantly lower (all P<0.05). Compared with β-HOB+CP group, the MMP in β-HOB+CP+Sap group was lower; the ratio of cell apoptosis, the expression of Caspase3 and Cleaved-caspase3, and the number of TUNEL staining positive cells were significantly higher (all P<0.05). Conclusions:β-HOB can alleviate the acute renal injury induced by cisplatin, which may be related to the reduction of apoptosis and inhibition of MAPK/NF-κB pathway.

Methylmalonic acidemia (MMA) is a series of rare inherited organic acid metabolic disorders with variable and nonspecific clinical manifestations, in particular neurological symptoms such as vomiting, lethargy, etc. Even with timely treatment, patients may still have various degrees of neurological complications and can even die. The prognosis is mainly related to the type of genetic variants, level of metabolites, newborn screening, onset of disease and early initiation of treatment. This article has reviewed the prognosis of patients with various types of MMA and factors that may affect it.
Infant, Newborn ; Humans ; Amino Acid Metabolism, Inborn Errors/complications* ; Prognosis ; Mutation ; Neonatal Screening ; Propionic Acidemia

Objective To investigate the clinical efficacy of endoscopic assisted minimally invasive trans foraminal lumbar interbody fusion(MIS-TLIF)and traditional open TLIF in the treatment of senile degenerative spondylolisthesis.Methods From January 2020 to March 2021,100 elderly patients with degenerative spondylolisthesis were selected and divided into MIS-TLIF group and TLIF group according to the surgical method,with 50 cases in each group.The preoperative and postoperative VAS,Japanese Orthopedic Association score(JO A)and Oswestry disability index(ODI),and the rate of interbody fusion and the incidence of complications were compared and analyzed between the two groups.Results In MIS-TLIF group,the operative time,intraoperative blood loss,incision length,postoperative drainage volume and hospital stay were(167.5±54.2)minutes,(173.8±47.1)ml,(3.5±0.7)cm,(69.6±16.3)ml,and(8.3±2.7)days,respectively.In the TLIF group,it was(136.3±38.9)minutes,(281.0±50.3)ml,(10.0±2.1)cm,(148.4±28.2)ml,and(11.2±3.1)days,respectively.The difference between the two groups was statistically significant(P＜0.05).The VAS,JO A and ODI scores of MIS-TLIF group were(2.17±0.62)points,(21.72±3.14)points and(13.22 ±2.43)points,respectively.The results in TLIF group were(3.24±1.06)points,(17.06±2.85)points and(16.83±2.87)points,respectively,and there was statistical significance between the two groups(P＜0.05).There was no significant difference in the rate of interbody fusion between the two groups at 12 months after operation(P＞0.05).The incidence of postoperative complications in MIS-TLIF group(8.00％)was significantly lower than that in TLIF group(24.00％,P＜0.05).Conclusion MIS-TLIF assisted by endoscope has the advantages of less trauma,faster recovery and less postoperative complications,and the short-term curative effect is more satisfactory than TLIF.

Objective:To explore the effect of Tai chi ball combined with Baduanjin in patients with acute myocardial infarction after PCI.Methods:From October 2018 to October 2019, a total of 118 patients with acute myocardial infarction after PCI in Department of Cardiology of Shangqiu First People's Hospital were selected as the research objects using the convenient sampling method, and divided into the observation group (57 cases) and the control group (61 cases) by the random number table method. The control group adopted conventional treatment and nursing, and the observation group conducted Tai Chi ball combined with Baduanjin exercise program on the basis of conventional treatment and nursing. One month after discharge, the ability of activity of daily living and quality of life were compared between the two groups.Results:One month after discharge, the total score of the ability of activity of daily living and the score of each dimension of the observation group were lower than those of the control group, and the differences were statistiocally significant ( P<0.05) ; the total score of the quality of life and the score of each dimension of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Tai Chi ball combined with Baduanjin can effectively improve the ability of activity of daily living and quality of life of patients with acute myocardial infarction after PCI.

[摘 要] 目的：探讨miR-203a-3p对胰腺癌BxPC-3细胞增殖、迁移和侵袭能力的影响。方法：运用癌症基因组图谱（TCGA）数据库筛选胰腺癌组织和癌旁组织中差异表达的miRNA，分析miRNA高表达与低表达时胰腺癌患者的生存率和临床分期；利用TarBase数据库分析miRNA与癌症相关的GO功能与KEGG通路，利用DIANA Tools、miRDB和TargetScan网站预测miR-203a-3p的靶基因。将miR-203a-3p mimic及NC mimic、miR-203a-3p inhibitor及NC inhibitor转染至BxPC-3细胞，用qPCR法检测胰腺癌细胞和胰腺正常上皮细胞HPNE中miR-203a-3p、miR-192-5p和miR-451a表达水平，以CCK-8法、Transwell小室法和克隆形成实验分别检测BxPC-3细胞的增殖、迁移、侵袭和集落形成能力。结果：通过TCGA数据库筛选出18个胰腺癌组织中差异表达的miRNA，其中miR-203a-3p、miR-192-5p、miR-451a具有物种保守性，且其与胰腺癌临床癌症分期、细胞周期和患者生存率相关（均P<0.05）；生物信息学网站预测显示miR-203a-3p的候选靶基因是PPM1A，PPM1A与多基因存在相互作用。miR-203a-3p、miR-192-5p和miR-451a在BxPC-3和Aspc-1细胞中均高表达（均P<0.01）。miR-203a-3p mimic组BxPC-3细胞中miR-203a-3p表达水平以及细胞增殖、迁移和侵袭能力均显著提高（均P<0.01）；miR-203a-3p inhibitor组细胞中miR-203a-3p表达水平以及细胞增殖、迁移和侵袭能力均显著降低（均P<0.01）。结论：miR-203a-3p在胰腺癌组织及细胞中均高表达，其表达与患者生存和临床分期相关，可调控BxPC-3细胞的增殖、迁移和侵袭能力。

Fluorescence spectroscopy was used to investigate the efficiency of coupling peptides to gold nanoparticles via 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride-N-hydroxysuccinimide (EDC-NHS).The experiment conditions including buffer solution, pH value and concentrations of buffer solution, concentrations of NHS and EDC, concentration ratios of NHS to EDC, and coupling reaction time on the coupling efficiency were investigated and optimized.The experimental results indicated that the optimized experimental conditions were as follows: 25 mmol/L HEPES buffer solution, pH 7.0;2∶1 of concentration ratio of NHS to EDC, 0.4 mol/L NHS, 0.2 mol/L EDC, and coupling reaction time of 24 h.This study may provide references for the relative research involving coupling peptide or protein with gold nanoparticles

Objective To investigate the viability of virtual touch tissue quantification (VTQ)technique in the prediction of acute rejection in transplanted liver.Methods One hundred and eighteen patients enrolled in the study were categorized into four groups:normal control (n =31),cirrhosis ( n =29),transplanted liver with acute rejection (n =28),transplant liver without any complications (n =30).All the patients were confirmed by pathology or clinical results.The VTQ of right robe of liver was obtained by a ultrasound system with VTQ technique and the data was compared among the four groups.Results The VTQ was (1.10 ± 0.29)m/s,(1.33 ± 0.33) m/s,(1.81 ± 0.47) m/s and (2.12 ± 0.59) m/s in normal control,transplanted liver without any complications,transplanted liver with acute rejection and cirrhosis group,respectively.It was significantly different in all four groups (P＜0.01).Patients with acute rejection were associated with the increase of the VTQ values (P＜0.01).Using a cutoff of VTQ＞1.36 m/s measured in the transplanted liver for prediction of acute rejection,the sensitivity and specificity were 82.1％ and 68.2％.Conclusions VTQ technique may have some clinical value in evaluation the acute rejection in transplanted liver.