This paper aims to study the effect of Ziziphi Spinosae Semen extracts on chronic unpredictable mild stress(CUMS)-induced depression-like and insomnia behavior models of mice. The CUMS-induced depression-like and insomnia behavior model of mice was established by CUMS treatment for three weeks. The mice were randomly divided into control group, model group, positive drug diazepam group(2 mg·kg~(-1)), as well as low-dose group(1.95 g·kg~(-1)), medium-dose group(3.9 g·kg~(-1)), and high-dose group(7.8 g·kg~(-1)) of Ziziphi Spinosae Semen extracts, with 18 mice in each group. On the 15th day of modeling, the drug was administered intragastrically once a day for one week. Then, the pentobarbital sodium cooperative righting experiment, open field experiment, and elevated plus maze experiment were carried out, respectively. The contents of neurotransmitters 5-hydroxytryptamine(5-HT) and 5-hydroxyindoleacetic acid(5-HIAA) in serum and thalamus of mice, as well as the levels of corticotropin releasing hormone(CRH), adrenocorticotropic hormone(ACTH), and corticosterone(CORT) in serum, were determined by enzyme-linked immunosorbent assay(ELISA). The neuron damage in the hippocampus of mice was observed by hematoxylin-eosin(HE) staining and Nissl staining. Western blot was used to detect the expressions of tryptophan hydroxylase 2(TPH2), serotonin transporter(SERT), monoamine oxidase A(MAOA), five prime repressors under dual repression binding protein 1(Freud1), synaptic plasticity-related proteins [cellular gene FOS(C-FOS), postsynaptic density protein 95(PSD95), synapsin 1(SYN1), and activity-regulated cytoskeleton-associated gene(ARC)], blood-brain barrier(BBB) permeability-related proteins [zonula occludens 1(ZO-1), occludin, and claudin 1], inflammatory factors [NOD-, LRR-and pyrin domain-containing protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), gasdermin D(GSDMD), caspase-3, and caspase-8], and antioxidant factors [nuclear factor erythroid 2-related factor 2(NRF2) and heme oxygenase 1(HO1)] in thalamic tissue of mice. The results indicated that compared with that in the model group, the sleep latency was significantly shortened, and the sleep duration was significantly prolonged in each dose group of Ziziphi Spinosae Semen extracts. The number of visits to the central area of the open field and the distance and time of visits were significantly increased in each dose group of Ziziphi Spinosae Semen extracts. In addition, the proportion of distance and time of entering the open arm area of the elevated plus maze was significantly increased in each dose group of Ziziphi Spinosae Semen extracts. The contents of 5-HT and 5-HIAA in serum and thalamus of mice increased to varying degrees in each dose group of Ziziphi Spinosae Semen extracts; the contents of CRH, ACTH, and CORT in serum of mice were significantly decreased. The protein expression of TPH2 was significantly increased. The protein expression of MAOA, SERT, and Freud1 was significantly decreased. Ziziphi Spinosae Semen extracts could also significantly reduce the protein expression of C-FOS but significantly increase the protein expression of PSD95, ARC, and SYN1. They could reduce the pathological damage of the hippocampus in mice and significantly increase the protein expression of ZO-1, occluding, and claudin 1. The protein expression of NLRP3, GSDMD, ASC, caspase-3, and caspase-8 in the thalamic tissue of mice was significantly decreased, and the protein expression of HO1 and NRF2 was significantly increased. In conclusion, Ziziphi Spinosae Semen extracts could effectively improve sleep disorders and depression-like behaviors in CUMS-induced model mice, which may be related to regulating the 5-HT anabolism process and hypothalamic-pituitary-adrenal(HPA) axis-related hormone levels, reducing pathological damage in the hippocampus, improving synaptic plasticity, repairing BBB integrity, and alleviating inflammatory response and oxidative stress damage.
Animals ; Ziziphus/chemistry* ; Mice ; Male ; Depression/psychology* ; Drugs, Chinese Herbal/administration & dosage* ; Sleep Initiation and Maintenance Disorders/psychology* ; Stress, Psychological/complications* ; Behavior, Animal/drug effects* ; Humans ; Disease Models, Animal

OBJECTIVE: To explore clinical efficacy of different technical combinations in treating ischemic diabetic foot (DF). METHODS: A retrospective analysis was conducted on 35 patients with DF who were treated with vascular interventional opening technique, periosteal distraction technique and bone cement coverage technique from January 2024 to November 2024. They were divided into comprehensive group and periosteal distraction group according to whether the vascular interventional opening technique was used in combination or not. There were 5 patients in comprehensive group, including 4 males and 1 female, aged from 59 to 73 years old with an average of (64.40±5.46) years old;the duration of diabetes ranged from 0.17 to 30.00 years with an average of (14.63±12.02) years;the courses of DF ranged from 30 to 150 days with an average of (84.00±61.48) days;2 patients were grade 2, 2 patients were grade 3, and 1 patient was grade 4 according to Wagner classification;combined vascular interventional opening, periosteal distraction and bone cement coverage surgery for treatment. There were 30 patients in periosteal stretch group, including 22 males and 8 females, aged from 58 to 86 years old with an average of (72.63±7.84) years old;the duration of diabetes was 10.00 (6.75, 16.75) years;the courses of DF was 30.00 (15.00, 37.50) days;14 patients were grade 2, 11 patients were grade 3, and 5 patients were grade 4 according to Wagner classification; combined periosteal distraction and bone cement coverage surgery for treatment. Changes of C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT), toe skin temperature, peripheral capillary oxygen saturation (SpO₂), and visual analogue scale (VAS) for pain were compared between two groups before operation and 1 week after operation. The number of operations, healing period, healing number, toe amputation number, preoperative fever situation and the number of complications were compared between two groups. RESULTS: Both groups were followed up for at least 6 months. There were no statistically significant differences in the number of operations, healing period, toe amputation rate, wound healing rate and complications between two groups (P>0.05). Before operation, the toe skin temperature of comprehensive group (26.98±0.88) ℃ was lower than that of periosteal distraction group (28.17±1.45) ℃, and the difference was statistically significant (P<0.05);while there were no statistically significant difference in CRP, IL-6, PCT, toe SpO2 and VAS between two groups (P>0.05). At 1 week after operation, IL-6, toe skin temperature, toe SpO₂ and VAS in comprehensive group were 12.29(7.92, 22.15) pg·ml-1, (36.02±0.23) ℃, (95.80±0.84) % and(1.40±0.55) respectively, while those in periosteal distraction group were 5.49(4.36, 7.45) pg·ml^-1, (31.36±1.57) ℃, (84.53±6.38) %, (2.20±0.81);and there were statistically significant differences between two groups(P<0.05). CRP, IL-6 and VAS at 1 week after operation in both groups were decreased compared with those before operation, and the differences were statistically significant(P<0.05). The toe skin temperature and SpO₂ were increased compared with those before operation, and the differences were statistically significant(P<0.001). CONCLUSION The multi-technique combination therapy, including vascular interventional opening technique, periostealdistraction technique and bone cement covering technique, could protect each other, enhance efficacy, effectively promote the wound healing of ischemic diabetic foot ulcer, and reduce the toe amputation rate. For moderate to severe ischemic DF, the combined use of periosteal distraction and bone cement coverage techniques has a satisfactory effect. For extremely severe ischemic DF with inflow tract lesions, vascular interventional opening techniques need to be added.
Humans ; Male ; Female ; Middle Aged ; Aged ; Diabetic Foot/surgery* ; Retrospective Studies ; Aged, 80 and over ; Ischemia/surgery* ; Interleukin-6/metabolism*

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective: To investigate the seroepidemiological characteristics of hepatitis B among outpatients in medical institutions in Jiaxing City, Zhejiang Province, so as to provide a reference for formulating region-specific hepatitis B prevention and control strategies. Methods: From April to June 2024, outpatients were selected as study subjects from sentinel medical institutions in Jiaxing City. Information such as gender and age was collected. Venous blood samples were obtained and serological markers including hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B e antigen (HBeAg), hepatitis B e antibody (HBeAb), and hepatitis B core antibody (HBcAb) were tested. Positive rates of hepatitis B virus (HBV) serological markers were analyzed by genders and ages. Results: A total of 1 468 outpatients were included, among whom 721 were males (49.11%) and 747 were females (50.89%). The mean age was (46.41±19.66) years. The positive rates of HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb were 7.29%, 44.75%, 1.84%, 23.50%, and 42.03%, respectively. The HBcAb positive rate in males was significantly higher than in females (46.05% vs. 38.15%, P<0.05), while no statistically significant gender differences were observed in the positive rates of other four HBV serological markers (all P>0.05). Except for HBsAb, the positive rates of the other four HBV serological markers showed statistically significant differences across different age groups (all P<0.05). Pairwise comparisons results showed that the HBsAg positive rates in age groups of 20-<40 years and 40-<60 years were 9.48% and 9.57%, respectively, which were higher than those in age groups of <20 years (1.43%) and ≥60 years (2.75%) (all P<0.05). A total of 17 HBV serological marker patterns were observed, among which the proportion of all markers negative was the highest, at 39.65%. The proportions of "small three positive" (HBsAg+, HBeAb+, HBcAb+) and "large three positive" (HBsAg+, HBeAg+, HBcAb+) patterns were 4.77% and 1.50%, respectively. Among HBsAg-positive individuals, the proportions of the "small three positive" pattern across age groups were 0, 45.45%, 90.00%, and 81.82%, while those of the "large three positive" were 0, 36.36%, 5.00%, and 0, with statistically significant differences across age groups (both P<0.05). Conclusions The positive rate of HBsAg among outpatients in medical institutions in Jiaxing City is relatively high, with a notable proportion of individuals showing either no immunity or non-response to vaccination. It is recommended to strengthen hepatitis B immunization efforts among the population aged 20-<60 years, and to enhance monitoring and interventional treatment for "small three positive" and "large three positive" patterns.

Objective To study the in vitro expression of three phenylalanine hydroxylase(PAH)mutants(p.R243Q,p.R241C,and p.Y356X)and determine their pathogenicity.Methods Bioinformatics techniques were used to predict the impact of PAH mutants on the structure and function of PAH protein.Corresponding mutant plasmids of PAH were constructed and expressed in HEK293T cells.Quantitative reverse transcription polymerase chain reaction was used to measure the mRNA expression levels of the three PAH mutants,and their protein levels were assessed using Western blot and enzyme-linked immunosorbent assay.Results Bioinformatics analysis predicted that all three mutants were pathogenic.The mRNA expression levels of the p.R243Q and p.R241C mutants in HEK293T cells were similar to the mRNA expression level of the wild-type control(P>0.05),while the mRNA expression level of the p.Y356X mutant significantly decreased(P<0.05).The PAH protein expression levels of all three mutants were significantly reduced compared to the wild-type control(P<0.05).The extracellular concentration of PAH protein was reduced in the p.R241C and p.Y356X mutants compared to the wild-type control(P<0.05),while there was no significant difference between the p.R243Q mutant and the wild type control(P>0.05).Conclusions p.R243Q,p.R241C and p.Y356X mutants lead to reduced expression levels of PAH protein in eukaryotic cells,with p.R241C and p.Y356X mutants also affecting the function of PAH protein.These three PAH mutants are to be pathogenic.[Chinese Journal of Contemporary Pediatrics,2024,26(2):188-193]

Microorganisms can form biofilms, complex, heterogeneous, multicellular communities that adhere to surfaces. Biofilm formation on the surface of structures in water will accelerate structures’ corrosion, seriously affect their service efficiency and life, and significantly impact the growth of animals, plants, and human life. Hence, clarifying the mechanism of biofilm formation contributes to developing new strategies to control biofilm formation on surface and then reduce infections, biofouling, and contaminations. Biofilm-targeting strategies include the regulation of established biofilms or the modulation of single-cell attachment. In most studies, physicochemical mechanism is frequently applied to explain the initial bacterial adhesion phenomena but rarely to explain other stages of biofilm formation. This review presents a five-step comprehensive description of the physicochemical process from film formation to biofilm maturation: (1) period of film formation; (2) period of bacterial adhesion; (3) period of extracellular-polymeric-substances (EPSs) membrane formation; (4) period of regulating biofilm by quorum sensing (QS); (5) period of biofilm maturation. We first clarify how the film formed by compound molecules affects the surface’s physicochemical properties and initial adhesion, summarizing many factors that affect bacterial adhesion. We then review the types of EPSs and signal molecules secreted by bacteria after irreversible adhesion, as well as their role and QS mechanism in biofilm maturation. Finally, we discuss how bacteria or microcolonies separate from the mature biofilm by physicochemical action and summarize the morphology and adhesion characterization methods after the biofilm matures. This review redefines the role of physicochemical in the whole process of biofilm formation and provides a theoretical basis for the prevention, removal, and utilization of biofilm and other related research fields.

During the progression of heart failure(HF),abnormal transduction of the transforming growth factor-β(TGF-β)/Smads signaling pathway is important mechanism of myocardial fibrosis(MF)in HF.TGF-β,a key factor in MF,is in an overexpression state in the process of MF in HF,and Smads is a major effector downstream of TGF-β.The TGF-β/Smads pathway induces abnormal proliferation of myofibroblasts,aggravates myocardial extracellular matrix deposition,and reduces the ability of the cardiac tissues to resist fibrosis,which plays a complex role in the pathogenesis of MF in HF.Traditional Chinese medicine(TCM)has the efficacy of unequivocal inhibiting myocardial collagen deposition,anti-MF,protecting the myocardium and improving cardiac function in the prevention and treatment of MF in HF and so on,and the TGF-β/Smads pathway is one of the key pathways through which TCM monomers,TCM combinations,and proprietary medicines can exert their cardioprotective effects on the HF.This paper reviews the existing experimental research results of TCM intervening in the TGF-β/Smads pathway for the treatment of MF in HF over the past 10 years,with a view to providing theoretical basis for the prevention and treatment of HF MF well as the development and of new drugs.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.