Objective: To investigate the current status of benefit finding among young and middle-aged patients with type 2 diabetes mellitus (T2DM) and analyze its influencing factors, so as to provide a reference for improving the level of benefit finding in this population. Methods: From November 2022 to May 2023, young and middle-aged patients with T2DM aged 18-59 years hospitalized in the endocrinology departments of 2 tertiary hospitals in Hengyang City, Hunan Province were selected as survey subjects by a convenience sampling method. Basic demographic information was collected using a general questionnaire survey. Benefit finding, resourcefulness, and stigma were evaluated using the Benefit Finding Scale, the Chinese Version of the Resourcefulness Scale, and the Type 2 Diabetes Stigma Assessment Scale, respectively. A multiple linear regression model was used to analyze the influencing factors of benefit finding among young and middle-aged patients with T2DM. Results: A total of 305 young and middle-aged patients with T2DM were investigated, including 222 males (72.79%) and 83 females (27.21%). There were 231 cases aged 45-59 years, accounting for 75.74%. The scores for benefit finding, resourcefulness, and stigma were (42.86±6.06), (75.12±11.30), and (41.20±10.10), respectively. Multiple linear regression analysis showed that young and middle-aged patients with T2DM who were male (β′=0.088), aged 18-<45 years (β′=0.083), absence of diabetes complications (β′=0.124), and had higher resourcefulness scores (β′=0.679) had higher levels of benefit finding, while patients with higher stigma scores (β′=-0.097) had lower levels of benefit finding. Conclusion The level of benefit finding among young and middle-aged patients with T2DM was moderate, and was related to gender, age, diabetes complications, resourcefulness, and stigma.

OBJECTIVES: To investigate the characteristics and clinical significance of anorectal manometry measurements in children with tethered cord syndrome (TCS) before and after surgery. METHODS: A retrospective study was conducted on 44 children with TCS treated at the Children's Hospital of Zhejiang University School of Medicine from January 2022 to September 2023. These patients were divided into effective subgroup (n=34) and non-effective subgroup (n=10) based on postoperative symptom improvement. Additionally, 34 children with functional constipation were selected as a control group. Baseline data and manometry measurements were compared between the preoperative TCS group and the control group, as well as between the non-effective and effective subgroups. RESULTS: The TCS group had lower short contraction time and defecation relaxation rate compared to the control group (P<0.05), while defecation residual pressure and maximum rectal tolerable threshold were higher than the control group (P<0.05). The length of the anal canal in the high-pressure zone in the effective subgroup was greater postoperatively than preoperatively (P<0.05), and the initial rectal sensation threshold decreased postoperatively (P<0.05). The non-effective subgroup had lower preoperative maximum rectal expulsion pressure compared to the effective subgroup (P<0.05). Postoperative rectal anal inhibition reflex values in the effective subgroup were higher than those in the non-effective subgroup (P<0.05). CONCLUSIONS There are some differences in anorectal dynamics between children with TCS and those with functional constipation. Maximum rectal expulsion pressure may be a key predictor of surgical outcomes. Surgery can alter certain defecation functions in some children.
Humans ; Male ; Anal Canal/physiopathology* ; Female ; Rectum/physiopathology* ; Child ; Child, Preschool ; Retrospective Studies ; Manometry ; Neural Tube Defects/physiopathology* ; Infant ; Defecation ; Adolescent ; Constipation/physiopathology* ; Clinical Relevance

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

Ischemic stroke (IS) is a prevalent neurological disorder often resulting in significant disability or mortality. Resveratrol, extracted from Polygonum cuspidatum Sieb. et Zucc. (commonly known as Japanese knotweed), has been recognized for its potent neuroprotective properties. However, the neuroprotective efficacy of its derivative, (E)-4-(3,5-dimethoxystyryl) quinoline (RV02), against ischemic stroke remains inadequately explored. This study aimed to evaluate the protective effects of RV02 on neuronal ischemia-reperfusion injury both in vitro and in vivo. The research utilized an animal model of middle cerebral artery occlusion/reperfusion and SH-SY5Y cells subjected to oxygen-glucose deprivation and reperfusion to simulate ischemic conditions. The findings demonstrate that RV02 attenuates neuronal mitochondrial damage and scavenges reactive oxygen species (ROS) through mitophagy activation. Furthermore, Parkin knockdown was found to abolish RV02's ability to activate mitophagy and neuroprotection in vitro. These results suggest that RV02 shows promise as a neuroprotective agent, with the activation of Parkin-mediated mitophagy potentially serving as the primary mechanism underlying its neuroprotective effects.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Mitophagy/drug effects* ; Resveratrol/analogs & derivatives* ; Neuroprotective Agents/pharmacology* ; Humans ; Neurons/metabolism* ; Reactive Oxygen Species/metabolism* ; Ischemic Stroke/genetics* ; Male ; Quinolines/pharmacology* ; Mice ; Fallopia japonica/chemistry* ; Mitochondria/metabolism* ; Reperfusion Injury/metabolism* ; Rats ; Mice, Inbred C57BL ; Disease Models, Animal

Objective To explore the efficacy of a compound nutrition preparation on wound healing after acute trauma and investigate the underlying mechanism primarily.Methods After skin wound model was successfully constructed on totally 60 male SD rats surgically,they were randomly divided into control group(CON group),whey protein group(WP group)and low-and high-dose nutritional formula groups(LDF and HDF groups),with 15 animals in per group.From the next day after surgery,the rats in each group were given corresponding nutritional interventions for 2 weeks.During the intervention,the wound conditions were observed and recorded,and the wound area was measured.The samples were collected on the 3rd,7th and 14th days after surgery,respectively.Serum albumin(ALB),prealbumin(PA),total protein(TP),inflammatory factors(TNF-α,IL-1β,IL-6 and IL-10),immunoglobulins(IgA,IgG and IgM)and hydroxyproline(Hyp)were detected by the corresponding reagent kits.The histopathologic changes of wound were observed with HE staining.Masson staining was used to observe the collagen fiber deposition in wound tissue.The angiogenesis of wound tissue was evaluated by immunohistochemical staining.Results Compared with the CON group,the wound healing speed,collagen synthesis and angiogenesis speed were significantly accelerated in the WP group,LDF group and HDF group(P＜0.05),and the effects were the most obvious in the HDF group.On the 3rd day after surgery,in the WP,LDF and HDF groups,the serum ALB,PA and TP levels were significantly increased(P＜0.05),serum TNF-α and IL-1β levels were obviously decreased(P＜0.05),and serum IL-10 level was notably increased(except WP group)when compared with the CON group.The serum IgG and IgM levels were significantly increased in the LDF group and HDF group(P＜0.05)and significant increment of IgA was only observed in the HDF group(P＜0.05).On the 7th day after modeling,the levels of ALB,PA and TP were significantly increased(P＜0.05),the levels of TNF-α,IL-1β and IL-6 were obviously decreased(P＜0.05),and the levels of IL-10 were remarkably increased(P＜0.05)in the HDF group than the CON group;The LDF group and HDF group had significantly elevated serum IgG and IgM levels(P＜0.05),but only the former group had statistically increased serum IgA level(P＜0.05).On the 14th day after modeling,the HDF group had significantly increased levels of ALB and TP(P＜0.05),decreased levels of IL-1β(P＜0.05),and raised levels of IgG and IgM when compared with the CON group(P＜0.05).Conclusion Our compound nutrition preparation promotes wound healing in rat model of acute trauma,which might be related to its improving the nutritional status,promoting collagen synthesis,and thus alleviating inflammatory response and enhancing immune function.

Objective To explore the application value of musculoskeletal ultrasound(MSUS)in grading acute gastrocnemius muscle injuries.Methods A retrospective analysis was conducted on ultrasound images of 291 patients who presented with sudden calf pain and suspected acute gastrocnemius muscle injury in the General Hospital of Central Theater Command from March 2019 to July 2024.The images were independently reviewed and assessed by three ultrasound doctors with different qualifications to determine the presence and grade of gastrocnemius muscle injury.The consistency of grading results among three doctors was compared.The diagnostic results of three doctors were summarized.Then,the diagnostic results of 29 patients who underwent routine MRI scans were compared with those of MSUS,and the agreement between the two imaging modalities was assessed using the Kappa test.Results Among the 291 patients,171 cases(58.8%)were diagnosed with gastrocnemius muscle injury,including 55 cases(32.2%)with grade Ⅰ,109 cases(63.7%)with grade Ⅱ,and 7 cases(4.1%)with grade Ⅲ.There were 159 cases(93.0%)of unilateral medial head injury,10 cases(5.8%)of unilateral lateral head injury,and 2 cases(1.2%)of bilateral medial and lateral head injury.Compared with patients without gastrocnemius muscle injury,patients with gastrocnemius muscle injury were older(P<0.05),with no significant difference in gender and laterality(P>0.05).No significant differences in baseline characteristics were found among patients with different grades of injury(P>0.05).The three doctors diagnosed 173(59.5%),171(58.8%),and 171(58.8%)cases of injury,respectively,with an inter-class correlation coefficient(ICC)of 0.947(P<0.001).Among 29 patients who underwent MRI,the diagnostic agreement between MRI and ultrasound for grade Ⅰ,Ⅱ and Ⅲ injury was 8(27.6%),18(62.1%)and 3(10.3%)for MRI;and 9(31.0%),17(58.6%)and 3(10.3%)for MSUS,respectively,with a Kappa value of 0.808(P<0.001).Conclusions MSUS is effective for assessing the grade of acute gastrocnemius muscle injury,and shows high diagnostic consistency among doctors with different qualifications.It is recommended as the preferred method for diagnosing gastrocnemius muscle injury.

2-(4-Methylthiazol-5-yl) ethyl nitrate hydrochloride (W1302) is a nitro containing derivative of clomethiazole, which is a novel neuroprotective agent with both carbon monoxide (NO) donor and weak γ-aminobutyric acid type A (GABA_A) receptor allosteric regulatory excitatory effect. The current study used a rat model of transient middle cerebral arteryocclusion (tMCAO) brain injury to evaluate the therapeutic effect of W1302 on ischemic stroke and explore its potential mechanisms of action. This experiment has been reviewed and approved by the Laboratory Animal Management and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences (ethical review forms No. 620, 632, 5013). The results showed that gavage administration of 1, 3, and 10 mg·kg^-1 of W1302 can significantly reduce the volume of cerebral infarction in rats with ischemia for 2 h and reperfusion for 24 h, and the therapeutic effect was better than that of 200 mg·kg^-1 of DL-3n-butylphthalide. W1302 significantly increased NO levels in blood and brain tissue. It increased cerebral blood flow and brain adenosine triphosphate (ATP) content after reperfusion, as well as, inhibited the expressions of inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in brain tissue. The time window of W1302 was between 120-180 min after ischemia. These research results demonstrated that W1302 could increase NO release, dilate blood vessels, and increase cerebral blood flow, improve energy supply to brain tissue and increase ATP levels, and inhibit neuro-inflammation, which playing the protective roles in tMCAO stroke model rats. This provides theoretical support for the clinical application of W1302 in the treatment of ischemic stroke.

Objective:To explore the feasibility of chemical exchange saturation transfer (CEST) imaging at 3.0 T MRI in quantifying renal redox metabolism in vitro models and experimental animals.Methods:Redox metabolites in vitro models with physiological concentrations were prepared, including reduced metabolites (glutamate, alanine, glutathione) and oxidized metabolites (2-ketoglutarate, pyruvate, glutathione disulfide, ammonium hydroxide). CEST examinations were performed at 3.0 T MRI. The imaging parameters were as follows: CEST images with different saturation pulse intensity (B 1) (1, 2, 3, 4 μT) and a fixed radio frequency (RF) duration of 2 000 ms; CEST images with different RF durations (1 500 and 2 000 ms) were acquired with a fixed B 1 value of 2 μT to obtain the optimal scanning parameters. CEST examinations with optimized parameters were performed on the left kidneys of seven healthy rabbits, and the differences in magnetic resonance ratio asymmetry (MTR asym) between rabbit renal cortex and outer medulla were measured. A paired t-test was used to compare the differences. Results:The optimal B 1 for CEST examination of redox metabolites was 2 μT, and the optimal RF duration was 2 000 ms. The MTR asym peaks of glutathione disulfide, glutathione, glutamic acid, and alanine were at 3.75, 3.5, 3, and 1.5 ppm, respectively. The MTR asym peaks of pyruvate, 2-ketoglutarate, and ammonium hydroxide were at 1 ppm. The MTR asym peak values of reduced metabolites were higher than those of oxidized metabolites. When the B 1 value was 2 μT and the RF duration was 2 000 ms, the MTR asym signal of the renal cortex was (2.60±1.10) %, (2.86±1.32) %, (3.04±1.06) %, and (2.98±0.91) % at 1, 3, 3.5, and 3.75 ppm, respectively. The MTR asym signal of the outer medulla was (1.00±0.56) %, (2.43±0.94) %, (2.29±0.88) % and (1.98±0.58) %, respectively. The MTR asym signal of the renal cortex was higher than that of the outer medulla, and the differences were statistically significant ( t=3.04, P=0.023; t=2.56, P=0.043; t=3.50, P=0.013; t=3.45, P=0.014). Conclusion:CEST imaging at 3.0 T MRI can be used to quantitatively evaluate redox metabolism of healthy rabbit kidneys in vitro model and normal experimental rabbits.

Objective To explore the clinical significance and mechanisms of chromatin licensing and DNA repli-cation factor 1(CDT1)in lung adenocarcinoma).Methods The gene expression samples of lung adenocarcinoma tissue and normal lung tissue were downloaded from the TCGA database,and perform differential analysis,GO a-nalysis,independent prognosis analysis,and correlation analysis with immunotherapy using R language.CDT1 ex-pression in lung adenocarcinoma and normal tissues was detected by PCR in clinical samples.The changes of cell proliferation and cycle in si-CDT1 knockdown group and si-NC control group were detected by flow cytometry.The invasive ability of each group was detected by Transwell.The expressions of CDT1,TPX2 and p53 in each group were detected by Western blot.Results The TCGA data analysis revealed CDT1 as a differentially expressed gene.GO analysis indicated that CDT1 was closely associated with the cell cycle.The high expression of CDT1 in lung adenocarcinoma tissues was validated in clinical samples.CDT1 could serve as an independent factor for predicting the prognosis of lung adenocarcinoma and had predictive value for immunotherapy in lung adenocarcinoma.Knock-down of CDT1 resulted in a significant decrease in cell proliferation ability compared to the control group,and cells were noticeably arrested in the G1 phase.Transwell assay results demonstrated a significant reduction in invasive capacity in the CDT1 knockdown group.Knockdown of CDT1 led to a significant decrease in TPX2 expression and a significant increase in p53 expression,while overexpression of CDT1 yielded the opposite effect.Conclusion Re-sults demonstrate the elevated expression of CDT1 in lung adenocarcinoma,its association with prognostic signifi-cance,and its impact on lung adenocarcinoma's occurrence and development by influencing TPX2 and p53.