Human umbilical cord mesenchymal stem cell （hUC-MSC） as a cell-based therapeutic strategy have demonstrated significant application potential in the field of intervention for neurodegenerative disease （NDD） due to their advantages such as self-renewal， multi-directional differentiation， and low immunogenicity. hUC-MSC effectively intervenes in the pathological features and neurological functions of various disease models such as Alzheimer disease， Parkinson’s disease， amyotrophic lateral sclerosis， and multiple sclerosis primarily through multiple mechanisms such as homing and differentiation， mediating paracrine actions and releasing exosomes， as well as immune regulation and anti-inflammation. Some clinical studies have also preliminarily verified their safety and effectiveness. Currently， its research still faces challenges such as immune rejection reactions requiring further observation， long-term safety needing evaluation， mechanisms of action not being fully elucidated， and slow progress in clinical trials. Future research needs to establish pharmaceutical standards for hUC-MSC， deepen their pharmacological mechanisms and clinical trials， ultimately providing new and effective drug treatment options for patients with NDD.

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Cognitive impairment is a major public health challenge facing global aging societies， and currently lacks effective treatment measures. Herb pair， characterized by their rigorous compatibility and synergistic effects， demonstrate unique advantages in clinical practice. Acorus tatarinowii-Polygala tenuifolia is a classic herbal pair for treating cognitive impairment， widely utilized in various traditional Chinese medicine formulations， such as Kaixin san， Shenghui tang， and Yuanzhi san. This article summarizes the pharmacological mechanisms of A. tatarinowii， P. tenuifolia and their compatible compound prescriptions in ameliorating cognitive impairment. It is found that they can exert effects in ameliorating cognitive impairment through mechanisms such as reducing amyloid β-protein deposition and inhibiting excessive phosphorylation of Tau protein， suppressing inflammatory responses， alleviating oxidative stress， protecting neurons and regulating neurotransmitters， modulating the structure and function of the blood- brain barrier， and regulating autophagy. Subsequently， in-depth analysis can be conducted on the active ingredients of A. tatarinowii- P. tenuifolia herb pair that ameliorate cognitive impairment， along with the addition of relevant clinical trials for verification. This will provide theoretical foundations and research approaches for the treatment of cognitive impairment using traditional Chinese medicine.

Objective:To investigate the trajectory of frailty in elderly patients on maintenance hemodialysis(MHD)following SARS-CoV-2 infection and its associated risk factors.Methods:This prospective cohort study focused on elderly patients who underwent baseline frailty assessment(T0)during hemodialysis treatment at Beijing Friendship Hospital for over 3 months between December 1st, 2022, and December 31th, 2022, and were diagnosed with SARS-CoV-2 infection.The Fried Frailty Phenotype was evaluated at 1 month(T1), 3 months(T2), and 6 months(T3)post-infection.Frailty trajectory after infection was analyzed using repeated measurement ANOVA.Patients were divided into stable/improvement or exacerbation groups based on their frailty status at T0 and T3, with logistic regression analysis employed to identify risk factors for different frailty trajectories.Results:A total of 130 elderly maintenance hemodialysis patients, with a median age of 66 years(range: 63-71 years)and 62 males(47.7%), were included in the study.Six months after the infection, a majority of surviving patients saw their frailty scores return to baseline levels.Specifically, 72 patients(55.4%)either maintained or improved to robust or pre-frail states, while 9 patients(6.9%)progressed to a pre-frail state, 18 patients(13.8%)progressed to a frail state, and 31 patients(23.8%)remained in a frail state.Results from multivariate logistic regression analysis indicated that low grip strength( OR: 6.30, 95% CI: 1.48-26.73)and all-cause hospitalization( OR: 5.01, 95% CI: 1.19-21.03)were identified as risk factors for non-frail patients transitioning to frailty( P<0.05). Conclusions:The majority of elderly maintenance hemodialysis patients who survived SARS-CoV-2 infection returned to their baseline level of frailty or showed improvement within 6 months.Non-frail patients with low grip strength or those who were hospitalized were more likely to deteriorate towards frailty.

OBJECTIVE To investigate the distribution and drug resistance of multidrug-resistant bacteria in the neonatal intensive care unit of a three-A children's hospital in Henan Province,and to provide reference for ational drug use in clinical practice.METHODS Clinical specimens from hospitalized newborns in neonatal intensive care unit from a three-A children's hospital from Jan.1,2019 to Dec.31,2023 were subjected to etiological exam-ination and drug sensitivity test,and to analyze the distribution and drug resistance of multidrug-resistant bacteri-a in hospitalized newborns.RESULTS During the 5-year period,1139 strains of multidrug-resistant bacteria were i-solated,including 229 gram-positive bacteria(20.11％)and 910 gram-negative bacteria(79.89％).There were 92 strains of methicillin-resistant Staphylococcus aureus(MRSA)(accounting for 8.08％),57 strains(accounting for 5.00％)of methicillin-resistant coagulase-negative Staphylococcus epidermidis and 28 strains(accounting for 2.46％)of methicillin-resistant coagulase-negative human Staphylococcus.370 strains(accounting for 32.48)of carbapenem-resistant Klebsiella pneumoniae(CRKP),268 strains(accounting for 23.53％)of extenspectrum β-lactamase-producing Escherichia coli and 85 strains(accounting for 7.46％)of K.pneumoniae,there were 767 sputum specimens(67.34％),160 blood specimens from peripheral intravenous puncture and central venous cath-eterization(PICC)(14.05％),63 bronchoalveolar lavage fluid specimens(5.53％),29 secretion specimens(eye and wound secretions)(2.54％),and 120 other specimens(10.54％).K.pneumoniae and E.coli producing su-per-broad spectrum β-lactamase,CRKP and MRSA were the main drug-resistant bacteria.CONCLUSION The sit-uation of drug resistance in neonatal intensive care unit is serious,therefore monitoring bacterial resistance should be strengthened according to the clinical laboratory results,and antibiotics should be applied rationally.

Objective:To investigate the predictive value of the Japanese nutritional risk index(NRI)for one-year all-cause mortality risk among elderly maintenance hemodialysis (MHD)patients.Additionally, it seeks to compare the predictive abilities of NRI with those of the geriatric nutritional risk index (GNRI)and the mini nutritional assessment short-form(MNA-SF).Methods:This research was conducted as a prospective cohort study.Elderly patients(aged ≥60 years)who underwent hemodialysis treatment at Beijing Friendship Hospital of Capital Medical University for more than three months between July and October 2019 were selected for inclusion.The NRI score was utilized to evaluate the nutritional status of the participants, with the maximum point of the Jordan index designated as the cut-off value, thereby categorizing patients into high-risk and low-risk groups.The follow-up period concluded in August 2020, with all-cause mortality serving as the primary outcome measure.Kaplan-Meier methods were employed to construct survival curves, and the Cox proportional hazards model was applied to analyze the association between NRI and all-cause mortality.Furthermore, area under the curve(AUC) of receiver operating characteristic(ROC)curves were utilized to compare the predictive values of the three nutritional assessment methods(NRI, GNRI, and MNA-SF)regarding mortality risk.Results:A total of 150 patients were included in the study, with a median age of 69(64.75) years.The cohort comprised 73 males(48.7%)and 77 females(51.3%). Based on the NRI, patients were categorized into a low-risk group(NRI<5; n=81, 54.0%)and a high-risk group(NRI ≥ 5; n=69, 46.0%). Of the 150 patients, 147 completed the follow-up.During the follow-up period, 15 patients died, with 13 from the high-risk group and 2 from the low-risk group.The Kaplan-Meier survival curve indicated that the 1-year cumulative survival rate for patients in the high-risk group was significantly lower than the low-risk group (log-rank χ2=11.71, P<0.001). Furthermore, multivariate Cox regression analysis revealed a significant association between NRI and 1-year all-cause mortality in elderly patients undergoing MHD ( HR=3.779, 95% CI: 1.036-13.783, P=0.044). Additionally, NRI demonstrated a high predictive value for 1-year all-cause mortality risk in elderly MHD patients, with an AUC of 0.755(95% CI: 0.654-0.855), a sensitivity of 86.7%, and a specificity of 59.1%.Its predictive capability was slightly superior to that of the GNRI(AUC=0.691, 95% CI: 0.548-0.835)and the MNA-SF(AUC=0.634, 95% CI: 0.475-0.793), although no statistically significant differences were observed( Z=0.880, 1.177, P=0.379, 0.239). Conclusions:The NRI score demonstrates effective predictive capability for one-year all-cause mortality risk in elderly MHD patients and may serve as a more suitable nutritional assessment method for this population.

Blood resource shortages, characterized by regional imbalance, seasonal fluctuations, and expiration-related wastage, pose a critical challenge to China's public health system. Cryopreserved red blood cell (RBC) technology, with its ultra-long preservation period, transfusion efficacy, and safety, offers a strategic pathway to alleviate chronic blood shortages and optimize resource allocation. This article systematically reviews the technological evolution of RBC cryopreservation, clarifies its core advantages, and identifies bottlenecks and improvement strategies in large-scale application. The establishment of a regularized cryopreserved RBC bank holds multidimensional strategic value; however, its practical implementation requires resolving challenges such as thawing timeliness, standardization gaps, and insufficient grassroots equipment. Future advancements should prioritize glycerol-free washing-free cryopreservation technologies, post-thaw extended preservation additive formulations, and intelligent thawing equipment to overcome throughput and spatiotemporal constraints, thereby providing robust technical support for building a regularized cryopreserved RBC bank and enhancing the efficiency of China's blood security framework.

[Objective] To explore the feasibility of using whole blood as a source of NK cells for allogeneic CAR NK cell therapy and activated NK cell reinfusion therapy, and initially construct a technical system for the separation and purification of NK cells from whole blood. [Methods] All peripheral blood mononuclear cells (PBMCs) were enriched from 400 mL of whole blood by manual separation and machine separation, respectively. The erythrocyte loss rate, PBMCs number, NK cell purity of the two methods were compared. NK cells were sorted from PBMCs by three separation and enrichment methods as immunomagnetic bead negative selection method, platelet lysate culture expansion and PERCOLL density gradient separation method, and the purity and yield of NK cells, the activity of NK cells and the tumor-killing ability of the three separation and enrichment methods were compared. [Results] The proportion of NK cells in the lymphocyte population was higher in the manual separation method than in the machine separation method[(13.16±5.16)% vs (8.56±3.92)%, P<0.05]; the number PBMCs was lower in the manual separation method than in the machine separation method[(4.09±1.80)×10⁸vs (6.49±2.16)×10⁸, P<0.05], and there was no difference in the red blood cell loss between the two methods (P>0.05). The purity of NK cells isolated and enriched from PBMCs by manual separation method using immunomagnetic was (96.77±2.31)%; the yield was (56.27±10.47)%; the inhibition of tumor proliferation was (38.67±14.05)%; and the tumor killing rate was (19.90±8.05)%. The purity of NK cells isolated and enriched from PBMCs by manual separation method using platelet lysis culture expansion method was the highest at day 7, which was (54.84±15.80)%; the cell expansion multiple could reach 16.92±6.28 at day 7; the in vitro tumor killing rate of NK cells was (15.83±5.5)%; the tumor inhibition rate was (44.33±13.5)%; and there was no difference in the toxicity and activity of NK cells between the two methods (P>0.05). The purity of NK cells isolated and enriched by PERCOLL density gradient separation method was (15.83±5.82)%, and the yield was (14±6.25)%, which was significantly lower than the other two methods. [Conclusion] PBMCs isolated from whole blood by manual separation and NK cells enriched by negative selection with immunomagnetic beads have the potential to provide NK cell materials for CAR-NK cell therapy, and NK cells enriched by platelet lysate-conditioned medium have the potential to provide NK cells for large-scale NK cell activation reinfusion therapy.

Objective To observe the effect of a heavy load exercise on the ultrastructure,function and fission of skeletal muscle mitochondria in rats,and to analyze the changes of the phosphorylation expression of mitochondrial fission protein and upstream kinase at different times postexercise,and to explore the effect of acute heavy load exercise on mitochondrial fission in skeletal muscle of rats and its possible mechanism.Methods Forty-eight adult male Sprague-Dawley rats were randomly divided in-to a quiet control group(C,n=8)and an exercise group(E,n=40).Rats in the E group exercised on a treadmill down a 16° decline at 16 m/min for 90 min and were further divided into 0 h,12 h,24 h,48 h,and 72 h postexercise subgroups.Soleus muscle was isolated and mitochondria were ex-tracted at the corresponding time points after exercise.The ultrastructure of mitochondria in the soleus muscle was observed using transmission electron microscopy,and mitochondrial quantity and morphomet-ric analysis were conducted.Moreover,the colocalization and quantity of dynamin-related protein 1(Drp1)and cytochrome C oxidease subunit Ⅳ(COXⅣ)in the soleus muscle were detected using im-munofluorescence double-labeling techniques.Meanwhile,protein levels of soleus musclep-Drp1Ser616,p-Drp1Ser637,p-extracellular regulatory protein kinaseThr202/Tyr204(p-ERKThr202/Tyr204),p-protein kinaseAThr197(p-PKAThr197),and mitochondrial NADH of ubiquinone oxidoreductase subunit B8(NDUFB8)and ubiqui-nol-cytochrome C reductase core protein 2(UQCRC2)were determined by using Western blotting.An-other twenty-four rats were randomly divided into a DMSO group(CD),a U0126 group(CU),an Ex-ercise+DMSO group(ED),and an Exercise+U0126 group(EU).Six mice in each group were giv-en a single intra-bitoneal injection of DMSO or ERK inhibitor U0126 20 min before acute downhill running.Then,their phosphorylated expressions of ERKThr202/Tyr204 and Drp1Ser616 in soleus muscle were de-tected by Western blotting.Results(1)From 0 h to 48 h after exercise,the soleus muscle mitochon-dria showed swelling,rounding,and uneven distribution of mitochondria,among which the degree of mitochondrial damage was the most serious at 12 h and 24 h after exercise.Moreover,the protein ex-pression of NDUFB8 and UQCRC2 in the mitochondria fractions from soleus muscle was significantly lower at 12 h post-exercise(P<0.05).(2)The co-localization of Drp1 and COXⅣ in the skeletal muscle increased significantly at 12 h to 24 h after a heavy load exercise compared with group C and group E0(P<0.01).Moreover,the mitochondrial area,circumference,aspect ratio and Ferret diameter in the skeletal muscle were significantly lower at 12 h to 24 h postexercise(P<0.05).Meanwhile,the number of mitochondria was significantly higher at 24 h after exercise(P<0.01).(3)The phosphoryla-tion of ERKThr202/Tyr204,PKAThr197 and Drp1Ser616 was significantly higher at 24 h after exercise(P<0.01),while that of Drp1Ser637 was significantly lower at 48 h and 72 h post-exercise(P<0.01).However,the phosphorylated expressions of ERKThr202/Tyr204 and Drp1Ser616 were significantly down-regulated by U0126 treatment before exercise.Conclusion A session of heavy load exercise caused mitochondrial structure and function damage and induced mitochondrial fission in the skeletal muscle,and then to maintain the homeostasis of skeletal muscle cells by cleaving damaged mitochondria.The mechanism of promot-ing skeletal muscle repair may be related to the positive and negative regulation of Drp1 activity by the phosphorylation of Drp1Ser616 and Drp1Ser637,respectively.Among them,the activation of ERKThr202/Tyr204 mediates the phosphorylation activation of Drp1Ser616,but PKAThr197 is not an upstream kinase that medi-ates the inactivation of Drp1Ser637 phosphorylation.