Evidence indicates that metabolic reprogramming characterized by the changes in cellular metabolic patterns contributes to the pathogenesis of pulmonary fibrosis(PF).It is considered as a promising ther-apeutic target anti-PF.The well-documented against PF properties of Tanshinone ⅡA(Tan ⅡA)have been primarily attributed to its antioxidant and anti-inflammatory potency.Emerging evidence suggests that TanⅡA may target energy metabolism pathways,including glycolysis and tricarboxylic acid(TCA)cycle.However,the detailed and advanced mechanisms underlying the anti-PF activities remain obscure.In this study,we applied[U-13C]-glucose metabolic flux analysis(MFA)to examine metabolism flux disruption and modulation nodes of Tan ⅡA in PF.We identified that Tan ⅡA inhibited the glycolysis and TCA flux,thereby suppressing the production of transforming growth factor-β1(TGF-β1)-dependent extracellular matrix and the differentiation and proliferation of myofibroblasts in vitro.We further revealed that Tan ⅡA inhibited the expression of key metabolic enzyme hexokinase 2(HK2)by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxia-inducible factor 1α(HIF-1α)pathway activities,which decreased the accumulation of abnormal metabolites.Notably,we demonstrated that Tan ⅡA inhibited ATP citrate lyase(ACLY)activity,which reduced the collagen synthesis pathway caused by cytosol citrate consumption.Further,these results were validated in a mouse model of bleomycin-induced PF.This study was novel in exploring the mechanism of the occurrence and develop-ment of Tan ⅡA in treating PF using 13C-MFA technology.It provided a novel understanding of the mechanism of Tan ⅡA against PF from the perspective of metabolic reprogramming.

The brain is a complex organ that requires precise mapping to understand its structure and function. Brain atlases provide a powerful tool for studying brain circuits, discovering biological markers for early diagnosis, and developing personalized treatments for neuropsychiatric disorders. Neuromodulation techniques, such as transcranial magnetic stimulation and deep brain stimulation, have revolutionized clinical therapies for neuropsychiatric disorders. However, the lack of fine-scale brain atlases limits the precision and effectiveness of these techniques. Advances in neuroimaging and machine learning techniques have led to the emergence of stereotactic-assisted neurosurgery and navigation systems. Still, the individual variability among patients and the diversity of brain diseases make it necessary to develop personalized solutions. The article provides an overview of recent advances in individualized brain mapping and navigated neuromodulation and discusses the methodological profiles, advantages, disadvantages, and future trends of these techniques. The article concludes by posing open questions about the future development of individualized brain mapping and navigated neuromodulation.

Neurogenesis decline in hippocampal dentate gyrus (DG) participates in stress-induced depressive-like behaviors, but the underlying mechanism remains poorly understood. Here, we observed low-expression of NOD-like receptor family pyrin domain containing 6 (NLRP6) in hippocampus of stress-stimulated mice, being consistent with high corticosterone level. NLRP6 was found to be abundantly expressed in neural stem cells (NSCs) of DG. Both Nlrp6 knockout (Nlrp6^-/-) and NSC-conditional Nlrp6 knockout (Nlrp6CKO) mice were susceptible to stress, being more likely to develop depressive-like behaviors. Interestingly, NLRP6 was required for NSC proliferation in sustaining hippocampal neurogenesis and reinforcing stress resilience during growing up. Nlrp6 deficiency promoted esophageal cancer-related gene 4 (ECRG4) expression and caused mitochondrial dysfunction. Corticosterone as a stress factor significantly down-regulated NLRP6 expression, damaged mitochondrial function and suppressed cell proliferation in NSCs, which were blocked by Nlrp6 overexpression. ECRG4 knockdown reversed corticosterone-induced NSC mitochondrial function and cell proliferation disorders. Pioglitazone, a well-known clinical drug, up-regulated NLRP6 expression to inhibit ECRG4 expression in its protection against corticosterone-induced NSC mitochondrial dysfunction and proliferation restriction. In conclusion, this study demonstrates that NLRP6 is essential to maintain mitochondrial homeostasis and proliferation in NSCs, and identifies NLRP6 as a promising therapeutic target for hippocampal neurogenesis decline linked to depression.

Objective:To explore the evaluation of nursing undergraduates on the effect of ideological and political teaching in nursing research courses.Methods:Using the purposive sampling method, a total of 19 undergraduate students from School of Nursing at Peking University who participated in nursing research ideological and political education courses were selected for face-to-face semi-structured interviews from March to June 2022. The interview data was analyzed using the Colaizzi phenomenological data analysis method.Results:A total of 19 students were interviewed, and the interviewees stated that through the study of nursing research ideological and political teaching courses, they had mastered scientific research methods, cultivated scientific thinking, strengthened innovation consciousness, expanded international vision and enhanced professional identity.Conclusions:This study is a beneficial attempt at ideological and political education in nursing research courses, providing a basis for the design, implementation and evaluation of ideological and political teaching of similar courses in the future.

Nicotinamide phosphoribosyl transferase (NAMPT) is considered as a promising target for cancer therapy given its critical engagement in cancer metabolism and inflammation. However, therapeutic benefit of NAMPT enzymatic inhibitors appears very limited, likely due to the failure to intervene non-enzymatic functions of NAMPT. Herein, we show that NAMPT dampens antitumor immunity by promoting the expansion of tumor infiltrating myeloid derived suppressive cells (MDSCs) via a mechanism independent of its enzymatic activity. Using proteolysis-targeting chimera (PROTAC) technology, PROTAC A7 is identified as a potent and selective degrader of NAMPT, which degrades intracellular NAMPT (iNAMPT) via the ubiquitin-proteasome system, and in turn decreases the secretion of extracellular NAMPT (eNAMPT), the major player of the non-enzymatic activity of NAMPT. In vivo, PROTAC A7 efficiently degrades NAMPT, inhibits tumor infiltrating MDSCs, and boosts antitumor efficacy. Of note, the anticancer activity of PROTAC A7 is superior to NAMPT enzymatic inhibitors that fail to achieve the same impact on MDSCs. Together, our findings uncover the new role of enzymatically-independent function of NAMPT in remodeling the immunosuppressive tumor microenvironment, and reports the first NAMPT PROTAC A7 that is able to block the pro-tumor function of both iNAMPT and eNAMPT, pointing out a new direction for the development of NAMPT-targeted therapies.

Epithelial ovarian cancer (EOC) is one of the leading causes of death from gynecologic cancers and peritoneal dissemination is the major cause of death in patients with EOC. Although the loss of 4.1N is associated with increased risk of malignancy, its association with EOC remains unclear. To explore the underlying mechanism of the loss of 4.1N in constitutive activation of epithelial-mesenchymal transition (EMT) and matrix-detached cell death resistance, we investigated samples from 268 formalin-fixed EOC tissues and performed various in vitro and in vivo assays. We report that the loss of 4.1N correlated with progress in clinical stage, as well as poor survival in EOC patients. The loss of 4.1N induces EMT in adherent EOC cells and its expression inhibits anoikis resistance and EMT by directly binding and accelerating the degradation of 14-3-3 in suspension EOC cells. Furthermore, the loss of 4.1N could increase the rate of entosis, which aggravates cell death resistance in suspension EOC cells. Moreover, xenograft tumors in nude mice also show that the loss of 4.1N can aggravate peritoneal dissemination of EOC cells. Single-agent and combination therapy with a ROCK inhibitor and a 14-3-3 antagonist can reduce tumor spread to varying degrees. Our results not only define the vital role of 4.1N loss in inducing EMT, anoikis resistance, and entosis-induced cell death resistance in EOC, but also suggest that individual or combined application of 4.1N, 14-3-3 antagonists, and entosis inhibitors may be a promising therapeutic approach for the treatment of EOC.

Objective To explore the effect of robot-assisted gait training on pelvis kinematics and the walking function of hemiplegic stroke survivors.Methods Thirty stroke survivors with hemiplegia were randomly divided into a treatment group and a control group,each of 15.Both groups were given routine clinical medication and rehabilitation training,while the treatment group was additionally provided with 20 minutes of robot-assisted gait training a day,6 d/wk for 8 weeks.Before and after the treatment,all of the patients' pelvis kinematics were assessed using 10 m walking speed (MWS),the timed up and go test (TUGT) and functional ambulation categorization (FAC).Results Before the treatment there were no significant differences between the two group in any of the measurements.After the treatment,significant improvement was observed in both groups in the vertical displacement and rotation and tilt angles of the pelvis while walking,with significantly more improvement in the treatment group than in the control group.There was also significant improvement in the average walking speed,TUGT time and FAC score of both groups,with significantly more improvement in the treatment group.Conclusion Robot-assisted gait training can significantly improve the pelvis control and walking ability of hemiplegic stroke survivors.

Objective To explore the the characteristics of non-motor symptoms of essential tremor(ET).Methods Totally 50 ET patients and 45 age-gender-matched healthy volunteers,admitted in Department of Neurology,The Second Affiliated Hospital of Zhejiang University School of Medicine from May 2015 to April 2016,were included.Clinical data and tremor analyses under different postures were obtained.The non-motor symptoms were evaluated using the Pittsburgh Sleep Quality Index(PSQI),Hamilton anxiety scale(HAMA),Hamilton's Depression Scale(HAMD),and the MOS item short from health survey (SF-36).Cognitive functions were evaluated by the Minimental state examination(MMSE).Results ET group had lower MMSE total score of (25.81 ±2.75 vs.28.16 ± 1.71),increased rate of dyssomnia (62.0％ vs.15.6％) and higher PQSI score (6.42±2.71 vs.3.84±2.13)compared with the control group(all P＜0.05).Moreover,more patients in the ET group had moderate and severe anxiety(60.0 ％ vs.37.8 ％),moderate and severe depression (34.0％ vs.15.6％)than the control group(both P ＜ 0.05).Anxiety and depression had effects on physical and mental health and were also related to the quality of life.Conclusions Non-motor symptoms,such as mild cognitive deficits,depression,anxiety and dyssomnia are common in ET patients.Furthermore,depression and anxiety have negative effects on physical and mental health.

BACKGROUND: Chitosan wound dressing has been extensively used in the treatment of wounds and burns, not only because of its bacteriastasis, hemostasis and promoting the wound healing, but also its good biocompatibility,biodegradability and biological functions.OBJECTIVE: To evaluate the efficacy and safety of chitosan wound dressing for deep second-degree burn, thereby providing clinical basis for its registration.METHODS: Sixty patients with deep second-degree burn were randomly allotted to two groups, and then subjected to the external application of chitosan wound dressing (experimental group) or chitosan biomedical dressing (control group),respectively. Then, the therapeutic efficacy was evaluated through healing time, recovering rate and pain scores, and the safety was evaluated through the incidence of adverse reactions and laboratory indexes before and after treatment.RESULTS AND CONCLUSION: There were no significant differences in the wound healing time [(21.23±6.84) days vs.(23.77±4.26) days], recovery rate and pain scores between the experimental and control groups at 14, 21 and 28 days after treatment (P > 0.05). The blood routine, liver function and kidney function indexes before and after treatment did not differ significantly between groups. Additionally, neither adverse nor severe adverse events occurred in the two groups.These results indicate that the therapeutic efficacy and safety of the chitosan wound dressing are equivalent to the control product in the treatment of deep second-degree burn.

Objective To investigate the changes in cognitive function in patients with early Parkinson's disease (PD) in a 5-year follow-up.Methods A total of 181 PD and 173 normal participants were recruited between January 2009 and January 2012 at the Department of Neurology,the Second Hospital of Jiaxing City.Regression analysis was used to evaluate the risk factors of cognitive impairment,and changes in subdomains of the Montreal Cognitive Assessment (MoCA) were compared annually with baseline data.Results Baseline clinical data were similar between the two groups.The level of cognitive impairment was positively correlated to the age of onset and the Hamilton Anxiety Scale (H AMD) (t =3.326,P＜ 0.05;t =5.211,P＜0.01),and negatively correlated to education level (t=-2.505,P＜0.05).There were no statistical differences in the first (26.5 ± 2.6),second (26.3±3.2) and third year (25.9±2.9) in the total scores of MoCA,which significantly increased in the forth (24.4 ± 2.3,P＜0.05) and fifth (24.1 ± 1.2,P＜0.05) year compared with baseline levels (26.7±2.9).However,in the control group,differences between any two years in total scores were not statistically significant (all P＞0.05).Seven subdomains of MoCA were attenuated,and four of them were significant different between the groups,including delayed recall,attention,abstraction task and orientation after the forth year of follow-up (all P ＜ 0.05).Meanwhile,visuospatial execution capacity was attenuated before the third year,and then rose markedly (P＜0.05).In the control group,the between-year differences of seven subdomains were not statistically significant (all P＞0.05).Conclusions Cognitive function of PD patients decreases significantly in some domains,such as delayed recall,attention,abstraction task and orientation after a five-year followup.