ObjectiveTo investigate the mechanism of salt processing of Psoraleae Fructus （PF） through modern analytical techniques and biotechnology， focusing on its effects related to hepatotoxicity and anti-osteoporosis activity. MethodsThe zebrafish model was utilized to evaluate the impact of PF and salt-processed Psoraleae Fructus （SPF） on the hepatotoxicity （using 134.17 ， 178.89， 268.34 mg·L^-1 as low， medium， and high dose groups of PF， 135.04， 180.06， 270.08 mg·L^-1 as low， medium， and high dose groups of SPF， respectively） and anti-osteoporotic activity （using 33.54 ， 67.08 and 134.17 mg·L^-1 as low， medium， and high dose groups of PF， 33.76， 67.52， 135.04 mg·L^-1 as low， medium， and high dose groups of SPF， respectively）， which was using alizarin red skull staining of zebrafish as an indicator of different batches of PF. The specific dosage of a batch of PF was taken as an example. Then ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry（UPLC-Q-TOF-MS） analysis was employed to identify the chemical composition of PF before and after salt processing， and PCA， OPLS-DA， and independent sample t-test were used to elucidating the compositional changes associated with the effects of salt processing on hepatotoxicity and anti-osteoporosis activity. ResultsUnder specific conditions， PF induced notable hepatotoxicity in zebrafish while simultaneously demonstrating protective effect against prednisolone-induced osteoporosis. In comparison to PF， SPF showed alleviated hepatotoxicity while retaining significant anti-osteoporosis activity. UPLC-Q-TOF-MS analysis revealed that after salt processing， the overall chemical composition of PF showed a downward trend， with 69 components showing a decrease in content， represented by psoralen， and 13 components showing an increase， represented by 4′-O-methyl psoralen B. Further multivariate statistical analysis revealed 11 key differential components before and after salt processing of PF， including psoralen and bakuchiol. ConclusionSalt processing effectively diminishes hepatotoxicity without impairing therapeutic efficacy against osteoporosis of PF， which may be related to the compositional changes before and after salt processing of PF and provides key evidence to reveal the scientific significance of salt processing of PF.

Objective:To analyze the association between inflammation-related dietary patterns and the risk for cognitive impairment in older adults aged ≥65 years in longevity areas in China by using reduced rank regression (RRR) analysis.Methods:This study used cross-sectional data from the 2021 Healthy Aging and Biomarkers Cohort Study, including the information about study participants' demographic characteristics, lifestyles, daily life activities, and disease histories. Dietary intake was obtained by using a simplified food frequency questionnaire. Cognitive impairment was evaluated based on the Mini-Mental State Examination Scale combined with years of education. Fasting venous blood samples were collected to detect inflammatory markers, especially high-sensitivity C-reactive protein (hs-CRP) and the platelet-to-lymphocyte ratio (PLR). RRR analysis was used to obtain inflammation-related dietary patterns using hs-CRP and PLR as response variables. Multivariate logistic regression model was used to analyze the association between dietary pattern score and the risk for cognitive impairment. Restricted cubic spline was used to explore the dose response relationship, and mediation analysis was used to quantify the mediating effects of hs-CRP and PLR.Results:Two dietary patterns were identified with RRR. The primary pattern was characterized by higher intakes of flour, red meat, and dairy products, and lower intake of fresh vegetables, explaining 6.84% of the variance in food intake and 0.50% of the variance in inflammatory markers. Compared with the T1 group, the T3 group had significantly higher risk for cognitive impairment ( OR=1.242, 95% CI: 1.034-1.491). Each one standard deviation increase in the dietary pattern score was associated with an 8.7% increase in the risk for cognitive impairment ( OR=1.087, 95% CI: 1.008-1.172), with a significant linear trend (overall-model P<0.001, non-linear P=0.295). Mediation analysis indicated that hs-CRP mediated 6.2% of the association between the dietary pattern and the risk for cognitive impairment. Conclusion:The inflammation- related dietary pattern characterized by higher consumption of flour, red meat, and dairy products and lower consumption of fresh vegetables is associated with an increased risk for cognitive impairment in older adults, and hs-CRP partially mediates this association.

One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

OBJECTIVE: To observe the effects of electroacupuncture (EA) on improving motor function and regulating microglial activation based on Notch receptor 1 (Notch1)/Hes family bHLH transcription factor 1 (Hes1) pathway in mice with Parkinson's disease (PD). METHODS: Thirty-six male C57BL/6 mice were randomly divided into a control group, a model group and an EA group, 12 mice in each group. PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days in the model group and the EA group. From the 1st day of modeling, EA was applied at "Baihui" (GV20) and bilateral "Shenshu" (BL23) in the EA group, with continuous wave, in frequency of 2 Hz and current of 2 mA, 15 min a time, once a day for 14 days continuously. The behavioral performance was evaluated by gait test, pole climbing test and hanging test, the number of positive cells of tyrosine hydroxylase (TH) and the co-expression positive cells of Notch1/ionized calcium binding adaptor molecule 1 (Iba-1) in the substantia nigra of midbrain was assessed by immunofluorescence, the protein expression of TH, α-synuclein (α-syn), Notch1, Hes1, Iba-1, inducible nitric oxide synthase (iNOS), Arginase-1 (ARG1), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10 was detected by Western blot, the mRNA expression of Notch1 and Hes1 was detected by real-time PCR. RESULTS: Compared with the control group, in the model group, the stride frequency was accelerated (P<0.001) and the stride length was shortened (P<0.001) for the four limbs, the pole climbing test time was prolonged (P<0.01) and the grip level was reduced (P<0.01); in the substantia nigra of midbrain, the number of positive cells of TH was decreased (P<0.001), the number of co-expression positive cells of Notch1/Iba-1 was increased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-1βand IL-6 was increased (P<0.01, P<0.05, P<0.001), the protein expression of TH, ARG1 and IL-10 was decreased (P<0.01, P<0.001), the mRNA expression of Notch1 and Hes1 was increased (P<0.01). Compared with the model group, in the EA group, the stride frequency was decelerated (P<0.001) and the stride length was increased (P<0.05, P<0.01, P<0.001) for the four limbs, the pole climbing test time was shortened (P<0.05) and the grip level was increased (P<0.05); in the substantia nigra of midbrain, the number of positive cells of TH was increased (P<0.01), the number of co-expression positive cells of Notch1/Iba-1 was decreased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-6 and IL-1β was decreased (P<0.05, P<0.01), the protein expression of TH, ARG1 and IL-10 was increased (P<0.05, P<0.001, P<0.01), the mRNA expression of Notch1 and Hes1 was decreased (P<0.05). CONCLUSION EA can improve the behavioral performance and protect the dopaminergic neurons in PD mice, its mechanism may relate to the inhibition of Notch1/Hes1-mediated neuroinflammation, thus inhibiting the microglial activation.
Animals ; Electroacupuncture ; Microglia/metabolism* ; Male ; Receptor, Notch1/metabolism* ; Parkinson Disease/physiopathology* ; Transcription Factor HES-1/metabolism* ; Mice ; Mice, Inbred C57BL ; Humans ; Signal Transduction

Objective To investigate the mechanism of microRNA-214-3p(miR-214-3p)targe-ting CHUK to regulate the nuclear factor(NF)-κB pathway in modulating the chemosensitivity of lym-phoma cells to ibrutinib.Methods The half-maximal inhibitory concentration(IC50)was used to verify the ibrutinib-resistant cell model.The expression levels of miR-214-3p and CHUK mRNA in tissues and cells were detected by quantitative real-time polymerase chain reaction(qRT-PCR).Western blotting(WB)was employed to assess CHUK protein levels.A dual-luciferase reporter assay was performed to confirm the direct targeting relationship between miR-214-3p and CHUK.Cell viability was measured using CCK-8 assay.Flow cytometry was used to evaluate cell apoptosis.The expression of the NF-κB p65 signaling pathway was detected by WB.Results The CHUK mRNA and CHUK protein expression levels were higher in ibrutinib-resistant cells than in control cells(P＜0.05).The qRT-PCR results showed that miR-214-3p was downregulated in ibrutinib-resistant cells.The dual-luciferase reporter assay confirmed that miR-214-3p directly targeted CHUK.Transfection of miR-214-3p mimics and knockdown of CHUK(si-CHUK)reduced the number of colony-forming cells,whereas transfection of miR-214-3p inhibitor increased the number of colony-forming cells(P＜0.05).Transfection of miR-214-3p mimics and knockdown of CHUK(si-CHUK)can promote apoptosis,while transfection of miR-214-3p inhibitor can inhibit apoptosis(P＜0.05).Inhibition of the NF-κB p65 pathway was observed in cells transfected with miR-214-3p mimics(P＜0.05).Conclusion MiR-214-3p may regulate the NF-κB p65 pathway by targeting the expression of CHUK,thereby enhancing the chemosensitivity of ibrutinib to lymphoma.

The clinical manifestations and genealogic test results of twin sisters with systemic lupus erythematosus (SLE) caused by the homozygous mutation of NCF1 treated at the Department of Pediatrics, Nanfang Hospital, Southern Medical University from May 2021 to January 2024 were reported.Case 1 (a 8-year-old girl) was admitted in May 2021 due to " epistaxis for two times and thrombocytopenia for more than 1 month", presenting tricytopenia, mainly thrombocytopenia.A homozygous mutation of NCF1 gene c. 269G > A (p.R90H) was detected in case 1, and she was subsequently diagnosed with SLE.Case 2 (a 11-year-old girl), the little sister of case 1, was admitted in January 2024 due to " repeated fever for more than 10 days, cough for 2 days, and convulsion once". The manifestations were reduced myelodysplasia, hemophagy accounted for 66%, and perineal ulcer during treatment.She was finally diagnosed with SLE and also had a homozygous mutation of NCF1 gene c. 269G > A (p.R90H).Their parents both carried the mutation.This case provides a reference for pathogenic mutations and phenotypes of NCF1.It suggests that close attention should be paid to the family history of patients in clinical diagnosis of SLE.

Objective To compare the effect of transcranial direct current stimulation(tDCS)combined with seated Taijiquan Yun-shou in different sequences on brain functional activation in healthy youths.Methods From September to December,2024,14 healthy young medical interns or probationers were recruited from the Fifth Hospital of Xiamen.They randomly completed three interventions in a crossover design:Yunshou training followed immediately by tDCS(Y-S group),tDCS intervention followed immediately by Yunshou training(S-Y group),and simultaneous implementation of tDCS intervention and Yunshou training(Sim group).Yunshou was practiced in a seated position.For tDCS,the anode was placed over the left primary motor cortex(M1),and the cathode over the right M1.Changes in oxyhemoglobin(HbO2)concentration in the regions of interest were mea-sured using functional near-infrared spectroscopy.Results Three cases dropped down.The brain regions with significant differences before and after intervention included:CH3,CH7 and CH23 of right prefrontal cortex(PFC)in Y-S group;CH12 of left PFC in S-Y group;and CH9,CH10 and CH25 of the left PFC,CH13 and CH14 of the left sensorimotor cortex(SMC),CH15 of the right pre-motor and supplementary motor cortex(PMC),and CH16 of the right SMC in Sim group(P<0.05).After inter-vention,HbO2 concentration was the highest in the bilateral PFC,bilateral PMC and left SMC in the Y-S group(P<0.05);and it was almost the same between Sim group and S-Y group(P>0.05),except that of the right PFC decreased in Sim group.Conclusion The sequential combination of brain-limb integrated regulation is a key factor influencing the immediate cor-tical activation pattern.

Objective:To analyze the association between inflammation-related dietary patterns and the risk for cognitive impairment in older adults aged ≥65 years in longevity areas in China by using reduced rank regression (RRR) analysis.Methods:This study used cross-sectional data from the 2021 Healthy Aging and Biomarkers Cohort Study, including the information about study participants' demographic characteristics, lifestyles, daily life activities, and disease histories. Dietary intake was obtained by using a simplified food frequency questionnaire. Cognitive impairment was evaluated based on the Mini-Mental State Examination Scale combined with years of education. Fasting venous blood samples were collected to detect inflammatory markers, especially high-sensitivity C-reactive protein (hs-CRP) and the platelet-to-lymphocyte ratio (PLR). RRR analysis was used to obtain inflammation-related dietary patterns using hs-CRP and PLR as response variables. Multivariate logistic regression model was used to analyze the association between dietary pattern score and the risk for cognitive impairment. Restricted cubic spline was used to explore the dose response relationship, and mediation analysis was used to quantify the mediating effects of hs-CRP and PLR.Results:Two dietary patterns were identified with RRR. The primary pattern was characterized by higher intakes of flour, red meat, and dairy products, and lower intake of fresh vegetables, explaining 6.84% of the variance in food intake and 0.50% of the variance in inflammatory markers. Compared with the T1 group, the T3 group had significantly higher risk for cognitive impairment ( OR=1.242, 95% CI: 1.034-1.491). Each one standard deviation increase in the dietary pattern score was associated with an 8.7% increase in the risk for cognitive impairment ( OR=1.087, 95% CI: 1.008-1.172), with a significant linear trend (overall-model P<0.001, non-linear P=0.295). Mediation analysis indicated that hs-CRP mediated 6.2% of the association between the dietary pattern and the risk for cognitive impairment. Conclusion:The inflammation- related dietary pattern characterized by higher consumption of flour, red meat, and dairy products and lower consumption of fresh vegetables is associated with an increased risk for cognitive impairment in older adults, and hs-CRP partially mediates this association.

Objective To compare the effect of transcranial direct current stimulation(tDCS)combined with seated Taijiquan Yun-shou in different sequences on brain functional activation in healthy youths.Methods From September to December,2024,14 healthy young medical interns or probationers were recruited from the Fifth Hospital of Xiamen.They randomly completed three interventions in a crossover design:Yunshou training followed immediately by tDCS(Y-S group),tDCS intervention followed immediately by Yunshou training(S-Y group),and simultaneous implementation of tDCS intervention and Yunshou training(Sim group).Yunshou was practiced in a seated position.For tDCS,the anode was placed over the left primary motor cortex(M1),and the cathode over the right M1.Changes in oxyhemoglobin(HbO2)concentration in the regions of interest were mea-sured using functional near-infrared spectroscopy.Results Three cases dropped down.The brain regions with significant differences before and after intervention included:CH3,CH7 and CH23 of right prefrontal cortex(PFC)in Y-S group;CH12 of left PFC in S-Y group;and CH9,CH10 and CH25 of the left PFC,CH13 and CH14 of the left sensorimotor cortex(SMC),CH15 of the right pre-motor and supplementary motor cortex(PMC),and CH16 of the right SMC in Sim group(P<0.05).After inter-vention,HbO2 concentration was the highest in the bilateral PFC,bilateral PMC and left SMC in the Y-S group(P<0.05);and it was almost the same between Sim group and S-Y group(P>0.05),except that of the right PFC decreased in Sim group.Conclusion The sequential combination of brain-limb integrated regulation is a key factor influencing the immediate cor-tical activation pattern.

Objective:To evaluate the predictive efficacy of multiple MRI radiomics-based machine learning models for the prognosis of patients with traumatic cervical spinal cord injury.Methods:A retrospective cohort study was conducted to analyze the plain cervical MRI imaging data of 135 patients with traumatic cervical spinal cord injury admitted to the Ninth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2020 to January 2024, including 107 males and 28 females, aged 24-89 years [(56.0±11.9)years]. The patients were randomly divided into training group ( n=94) and test group ( n=41) at a ratio of 7∶3. According to the Japanese Orthopedic Association (JOA) score, 56 patients had no self-care ability (0-8 points), while 79 patients had self-care ability (9-17 points). The cervical spinal cord injury areas of all the patients were delineated. After standardizing the signal intensity distribution of the images using Z-Score, the radiomics features of the injury areas were extracted, on which the dimensionality reduction was performed by the Pearson correlation coefficient method. In the training group, the Lasso regression model was used to screen the radiomics features significantly related to the prognosis of no self-care ability and the features were then input into seven classifiers to construct prediction models, including the support vector machine, random forest, extremely randomized tree, light gradient boosting machine, adaptive boosting, naive Bayes, and K nearest neighbor. In the test group, the predictive performance of each model was evaluated through accuracy, sensitivity, specificity, precision, F1 score, area under the receiver operating characteristic (ROC) curve (AUC), and Hosmer-Lemeshow (H-L) goodness-of-fit test. The clinical applicability of each model was evaluated through clinical decision curve analysis (DCA). Results:A total of 14 radiomics features were selected, including 1 first-order feature and 13 texture features. In the test group, the accuracy rates of the 7 models of support vector machine, random forest, extremely randomized tree, light gradient boosting machine, adaptive boosting, naive Bayes, and K nearest neighbor were 0.85, 0.81, 0.90, 0.90, 0.71, 0.73 and 0.71, respectively; the precision rates were 1.00, 0.95, 0.92, 0.96, 0.72, 0.75 and 0.88, respectively; the sensitivity rates were 0.76, 0.72, 0.92, 0.88, 0.84, 0.84 and 0.60, respectively; the specificity rates were 1.00, 0.94, 0.88, 0.94, 0.50, 0.56 and 0.88, respectively; the F1 scores were 0.86, 0.82, 0.92, 0.92, 0.78, 0.79 and 0.71, respectively; the AUC values were 0.93, 0.92, 0.94, 0.97, 0.58, 0.67 and 0.88, respectively; the P values of the H-L goodness-of-fit test were 0.211, 0.112, 0.218, 0.089,<0.001,<0.001 and 0.105, respectively; the DCA results indicated that the support vector machine exhibited a clinical benefit rate greater than 0 within the 0-1 interval, surpassing the performance of the other models. Conclusions:Four MRI radiomics-based models, including support vector machine, random forest, extremely randomized tree, and light gradient boosting machine, have good predictive efficacy for the prognosis of patients with traumatic cervical spinal cord injury. Among them, the support vector machine model has the best clinical applicability.