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 Cheng's Juanbi Decoction(CSJBD)is a classic traditional Chinese medicine formula for treating rheumatoid arthritis(RA),exhibiting significant clinical efficacy,but the underlying mechanisms remain unclear.We investigated whether CSJBD inhibited RA pathology by blocking the WTAP-Wnt7b-Wnt/β-catenin signaling axis using a collagen-induced arthritis(CIA)mouse model and fibroblast-like synoviocytes(FLSs)derived from RA patients(RA FLSs)and examined the underlying mechanisms.Methods We conducted in vivo experiments.Male C57BL/6 mice weighing 17 to 20 g were used to establish the CIA model.The mice were assigned to 6 groups,including the normal group,the model(CIA)group,the model+CSJBD-L(8.1 g/kg)group,the model+CSJBD-M(16.2 g/kg)group,the model+CSJBD-H(32.4 g/kg)group,and the model+leflunomide(LEF)(0.05 mg/10 g)group,with 10 mice in each group.CSJBD was administered twice daily via gastric gavage,while LEF was administered once daily via gastric gavage,for a duration of 28 days.We also conducted in vitro experiments.RA FLSs were assigned to 4 groups,including the RA FLSs+CSJBDS-L group receiving 10%CSJBDS-containing serum,the RA FLSs+CSJBDS-M group receiving 15%CSJBDS-containing serum,the RA FLSs+CSJBDS-H group receiving 20%CSJBDS-containing serum,and the RA FLSs+NC group(negative control).To study whether WTAP regulated Wnt7b,RA FLSs were divided into the RA FLSs group,the RA FLSs+si-WTAP#3 group,the RA FLSs+si-WTAP#3+Wnt7b-OE group,and the RA FLSs+si-WTAP#3+Wnt7b-NC group.To study the underlying mechanism by which CSJBT affected RA FLSs,RA FLSs were divided into the RA FLSs group,the RA FLSs+CSJBDS-M group,the RA FLSs+CSJBDS-M+Wnt7b-OE group,and the RA FLSs+CSJBDS-M+NC group.We used ultra-high performance liquid chromatography(UPLC)to identify and quantify key monomer compounds from CSJBD as quality criteria for CSJBD preparation.Bioinformatics,CCK-8,RT-qPCR,Western blot,immunofluorescence,and related methods were employed to assess the therapeutic efficacy and underlying mechanisms of CSJBD in treating RA.Results According to the UPLC analysis,ferulic acid,osthole,mulberroside A,notopterol,and gentiopicroside were identified as quality control standards for the preparation of CSJBD formula.CSJBD improved RA pathology in CIA mice,reduced the levels of interleukin(IL)-6,IL-1β,IL-8,and tumor necrosis factor-α(TNF-α)in their serum,and decreased the expression of RA pathological genes MMP3 and fibronectin,with the difference between groups being statistically significant.Bioinformatics analysis suggested that CSJBD might inhibit RA pathology by suppressing the Wnt/β-catenin signaling pathway through Wnt7b.Experimental results showed that the expression of WTAP and Wnt7b was significantly increased in RA.After knocking down WTAP,the expression of Wnt7b was significantly reduced,and the Wnt/β-catenin signaling pathway was also inhibited,with the difference between groups being statistically significant(P<0.05),confirming that WTAP regulated the pathway via Wnt7b.According to experimental verification,CSJBD significantly inhibited the Wnt/β-catenin signaling pathway and the proliferation of RA FLSs.Wnt7b overexpression reversed the inhibitory effect of CSJBD on the Wnt/β-catenin signaling pathway and the proliferation of RA FLSs,indicating that Wnt7b is the direct target of CSJBD.Conclusion CSJBD inhibits RA pathology by blocking the WTAP-Wnt7b-Wnt/β-catenin signaling axis,with Wnt7b identified as a direct therapeutic target of CSJBD.

Objective:To investigate the effect of fecal microbiota transplantation(FMT)on unilateral ureteral obstruction(UUO)-induced renal fibrosis in mice.Methods:Male C57BL/6J mice were randomly divided into the control group,UUO group,UUO+FMT group and myeloid-derived suppressor cells(MDSCs)transfer group.The latter 3 groups were constructed renal fibrosis models by UUO,the UUO+FMT group received FMT from control mice after UUO surgery,and the MDSCs transfer group underwent splenectomy and intravenous injection of MDSCs from the peripheral blood of the UUO+FMT group.Renal tissue specimens were collected at 14 d after UUO for HE and Masson staining.TNF-α and IL-10 expression levels were detected by real-time fluorescence quantitative PCR(qRT-PCR),Western blot and immunofluorescence staining.Results:HE staining showed that the renal tissue structure of the control group was normal.The UUO group showed significant dilatation of renal tubules accompanied by obvious inflammatory cell infiltration.However,the renal lesions in the UUO+FMT group and MDSCs transfer group were significantly improved compared with those in the UUO group.Masson staining showed that the positive area of collagen deposition significantly increased in the UUO group compared with the control group,while the positive area of collagen deposition decreased in the UUO+FMT group and MDSCs transfer group compared with the UUO group.The results of qRT-PCR,Western blot and immunofluorescence showed that the expression levels of TNF-α and IL-10 were elevated in renal tissues of the UUO group compared with the control group.Compared with the UUO group,the expression level of TNF-α decreased while IL-10 increased in the UUO+FMT group and MDSCs transfer group.Conclusions:FMT reduces the expression of TNF-α and increase the expression of IL-10 in the kidney of UUO mice,and alleviates renal fibrosis.FMT may exert a nephroprotective effect by regulating MDSCs.

Objective To investigate the effects of microgravity environment on hibernating myoblasts.Methods Hibernating myoblasts were cultured under real and simulated microgravity conditions for 10 days.RNA-seq analysis and immunofluorescence are used to analysis the impact of microgravity environment on cell growth and gene expression of myoblasts.Results Under the microgravity conditions,genes associated with proliferation were upregulated.Under simulated microgravity,there were more and higher proportion of Ki67 positive cells compared to normal gravity conditions.Conclusion The microgravity environment promotes the proliferation of hibernating myoblasts.

Hepatic venous pressure gradient (HVPG) is the "gold standard" for the diagnosis of portal hypertension, which could be applied in the evaluation of liver cirrhosis. Combined use of HVPG with model for end-stage liver disease (MELD) scoring system may more accurately match the donors and recipients undergoing liver transplantation for liver cirrhosis, select the appropriate timing of surgery, and provide guidance for bridging treatment for patients on the waiting list for liver transplantation. Besides, HVPG may also predict clinical prognosis of liver transplant recipients, and provide evidence for early detection and intervention of potential complications. Therefore, the value of HVPG in preoperative evaluation and prognosis prediction of liver transplant recipients was reviewed, aiming to provide guidance for clinical diagnosis and treatment of liver transplant recipients before and after surgery.

Objective To investigate the efficacy and influencing factors of allo-HSCT in the treatment of MDS patients with ASXL1+.Methods The second-generation sequencing technique was used to detect 22 gene mutations in 247 newly diagnosed MDS patients in our hospital.The patients were divided into chemotherapy group and transplant group according to treatment style.The differences of OS and PFS between the two groups were compared,and the influencing factors of prognosis of transplant patients were analyzed.Results ASXL1+ was detected in 75 patients(30.36%),with a median mutation ratio of 42.93(18.10,58.39)%,10 received supportive treatment,43 received demethylation therapy or demethylation combined with pre-excitation therapy,and 22 received allo-HSCT.2-year PFS rate and OS rate of transplantation group were significantly higher than that of chemotherapy group(P<0.05).The 2-year OS rate in the low ASXL1 mutation load group(VAF≤42.93%)was significantly higher than that in the high ASXL1 mutation load group(VAF>42.93%)(P<0.05).In the context of allo-HSCT in patients with ASXL1+,2-year OS and PFS rates were significantly reduced in patients with RUNX1+ or ASXL1+(P<0.05);Multivariate analysis showed that high mutation load of ASXL1 or U2AF1+ were independent risk factors for OS in transplant patient(P<0.05).U2AF1+ were the risk factors for PFS(P<0.05).Conclusion allo-HSCT significantly improved the prognosis of patients with ASXL1+ MDS.High ASXL1 mutation load or U2AF1+ were independent risk factors affecting the outcome of allo-HSCT.

The complement system is an important part of the innate immune system,including more than 50 secretory proteins and membrane-bound proteins,and it contributes to the clearance of apoptotic cells and invading pathogens to limit inflammatory immune responses and maintaining brain homeostasis.Complement activity is strictly regulated to protect cells from random attacks or to prevent the deposition of complement proteins in physiological cases.However,overactivation or abnormal regulation of the complement cascade in the brain can lead to neuronal damage and brain dysfunction.Recent studies have pointed out that changes in complement molecules exist in patients with psychiatric diseases and play an important role in the occurrence and development of diseases by regulating the function of neurons and glial cells.Therefore,summarizing the latest research progress of complement system in psychiatric diseases such as schizophrenia,autism spectrum disorder,major depression,bipolar disorder and anxiety disorder can provide new ideas for preventing and controlling psychiatric diseases caused by abnormal activation of complement system.

Objective:To analyze the clinical characteristics of novel coronavirus (COVID-19) infection in liver transplant recipients.Methods:Clinical data of 130 liver transplant recipients with COVID-19 infection followed in Hebei Medical University Third Hospital from November 2022 to January 2023 were retrospectively collected, including 103 males and 27 females, aged (53.6±11.4) years. The severity of COVID-19 infection, its clinical symptoms, and negative conversion time for each recipient were analyzed and compared.Results:For the disease severity, 121 (93.1%) were mild, 5 (3.8%) were moderate, 3 (2.3%) were severe, and 1 (0.8%) was critically severe. The most common symptoms in the 126 patients with mild to moderate COVID-19 infection were successively fever, fatigue, cough and myalgia, with a negative conversion time of (10.1±4.5) (3.0-29.0)d. In those who underwent transplantation less than 12 months ( n=28), those who were taking mycophenolate mofetil ( n=53) and those who were taking methylprednisolone ( n=10), the negative conversion time was (11.6±5.1) d, (11.4±5.4) d, and (13.4±6.4) d, respectively, longer compared to those who underwent transplantation more than 12 months (9.7±4.2 d, n=98), and who were not taking mycophenolate mofetil (9.2±3.4 d, n=73) or methylprednisolone (9.8±4.2 d, n=116, all P<0.05). The negative conversion times were longer in recipients with symptoms (eg. fatigue and cough) than those in asymptomatic recipients (11.0±5.1 d vs. 9.0±3.3 d, t=2.64, P=0.009, and 11.4±5.2 d vs. 9.0±3.4 d, t=2.92, P=0.004). Conclusion:The COVID-19 infection in liver transplant recipients was mainly mild and moderate. The most common symptoms are fever, fatigue, cough and myalgia. The short time (less than 12 months) after liver transplantation, oral mycophenolate mofetil and methylprednisolone, with symptoms (fatigue and cough) could be associated with a prolonged negative conversion time.

Taking the curriculum integration of skin diseases as an example, this paper summarizes the skin diseases with high incidence in the army such as acne, tinea pedis, warts, folliculitis, corns and calluses, sunburns, etc. The results have been applied to the integration of the skin disease curriculum in Air Force Medical University. During the course integration process, we integrated the courses of dermatology, plastic surgery and burn surgery together, and simplified the teaching content according to the "organ-system" orientation and features of military medical university. In the teaching process, the PBL teaching method was used to guide the students to discuss with the problems. At the end of the course, the students were assessed by tests, and the satisfaction evaluation were carried out. The results showed that the application of high incidence of skin diseases in the army in curriculum integration can help improve the teaching effect and the satisfaction of students, which will provide a certain reference for the curriculum integration reform of military medical universities.

Objective:To explore the effect of social isolation (SI) on cognitive function and the phenotypic transition of hippocampal astrocytes in mice.Methods:Twenty male C57BL/6 mice aged 3-4 weeks were randomly divided into normal group house (GH group) and social isolation group (SI Group). The mice in SI group were fed one per cage for 8 weeks to establish a social isolation model, and the mice in GH group were fed five per cage. The cognitive function of mice was detected by the novel object recognition test and novel location recognition test. The expression of astrocyte marker glial fibrillary acidic protein (GFAP) was detected by immunohistochemistry, RT-PCR and Western blot.The astrocyte morphology change was quantitatively analyzed by Sholl Analysis.The expression of the hippocampal A1-A2 astrocytes markers proteasome subunit beta 8(PSMB8) and a member of the S100 family of Ca 2+ -binding proteins (S100A10) were determined by RT-PCR and Western blot. Statistical analysis was performed using GraphPad Prism 6.0 software, and t-test was used for comparison between two groups. Results:The results of cognitive function showed that the exploration index of novel object ((-5.54±3.30)%, (33.42±7.14)%; t=4.680, P=0.001) and the exploration index of novel location((-7.96±4.81)%, (23.55±8.20)%; t=3.670, P=0.008) in SI group were both lower than those in GH group.Immunohistochemical results showed that the number of GFAP positive cells in hippocampus of SI group was significantly lower than that of GH group((369.90±42.97), (544.90±57.64); t=2.480, P=0.023). The results of Sholl analysis showed that the protuberance of hippocampal astrocytes in SI Group retracted.There were significant differences in the number of intersections between the two groups at 6, 8, 10, 12, 14 and 16 μm away from astrocyte cell body(all P<0.05). Western blot showed that the expression of GFAP protein in SI group was lower than that in GH group((0.85±0.05), (1.03±0.06); t=2.527, P=0.028). The results of PCR showed that the expression of GFAP mRNA in SI group was lower than that in GH group ((0.83±0.05), (1.00±0.03); t=2.970, P=0.018). The expression of A1 phenotypic marker PSMB8 mRNA ((1.58±0.17), (1.00±0.06); t=2.931, P=0.011) and A2 phenotypic marker S100A10 mRNA ((1.52±0.14), (1.00±0.07); t=3.121, P=0.007) in the hippocampus of SI group were higher than those in GH group.Compared with the GH group, the expression of the neurotrophic factors IGF-1 mRNA in the SI group was down-regulated ((0.73±0.07), (1.00±0.08); t=2.327, P<0.05), while the expression of LCN2 mRNA((1.12±0.03), (1.00±0.03), t=2.575, P<0.05), IL-1β mRNA(1.76±0.19), (1.00±0.07), t=3.460, P<0.01) and TNF-α mRNA((2.18±0.42), (1.00±0.07), t=2.427, P<0.05) were up-regulated in the SI group. Conclusion:The pathological mechanism of social isolation-induced cognitive impairment in mice may be related with the phenotypic changes of astrocytes.