ObjectiveTaking Aurantii Fructus Immaturus juice（AFI）-processed Atractylodis Macrocephalae Rhizoma（AMR） as an example， this study aims to systematically compare the volatile and non-volatile components of AMR and its processed products， investigate the key differential components， evaluate their anti-inflammatory activities， and elucidate the synergistic mechanism of processing. MethodsThe chemical compositions of volatile and non-volatile components in AMR and AFI-processed AMR were systematically characterized using gas chromatography-mass spectrometry（GC-MS） and ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， with relative mass fractions and response values determined separately. Volatile components were identified through searches in the National Institute of Standards and Technology（NIST）17 database， comparison with retention index（RI） and fragmentation pattern matching. Non-volatile components were identified by searching Waters Traditional Chinese Medicine （TCM） spectral library， in conjunction with PubChem and MassBank， characteristic fragmentation patterns and response values were also used to support identification. Differential components were screened using principal component analysis（PCA）， orthogonal partial least squares-discriminant analysis（OPLS-DA）， with variable importance in the projection（VIP） value >1. Components with high log₂fold change（FC） among major differential groups were selected as those exhibiting significant changes before and after processing. The anti-inflammatory activity of the differential compounds was evaluated by assessing their effects on nitric oxide（NO） production in a lipopolysaccharide（LPS）-induced RAW264.7 macrophage model. Enzyme-linked immunosorbent assay（ELISA） was used to detect the effects of the differential components on tumor necrosis factor（TNF）-α， interleukin（IL）-1β， IL-6， and monocyte chemotactic protein（MCP）-1 levels， and immunofluorescence（IF） was employed to assess their effects on nuclear transcription factor（NF）-κB p65 translocation， thereby elucidating the underlying molecular mechanisms. ResultsA total of 36 compounds were identified in the volatile components of AMR and AFI-processed AMR， among which， sesquiterpenes and monoterpenes were significantly increased after processing. In the non-volatile components， 36 compounds were identified， and the main differential components were flavonoids， sesquiterpenoids， and triterpenoids. Flavonoids were the primary differential components distinguishing AMR from its processed products， representing compounds directly introduced during processing. Five compounds， including atractylenolide Ⅲ， tangeritin， nobiletin， hesperidin and narirutin， were selected as representatives of three classes based on their most prominent differential expression among different compound types for subsequent anti-inflammatory activity studies. The results showed that 100 μmol·L^-1 tangerine and narirutin could significantly inhibit LPS-induced NO production（P<0.01） in a concentration-dependent manner. Tangeritin was able to significantly inhibit the levels of TNF-α and MCP-1 secreted by RAW264.7（P<0.05）， while narirutin significantly inhibited the levels of TNF-α， IL-1β， MCP-1 and IL-6（P<0.01）. IF revealed that both tangeritin and narirutin significantly blocked the translocation of NF-κB p65 from the cytoplasm to the nucleus. ConclusionAFI-processed AMR significantly alters the chemical composition profile of AMR， and the newly introduced flavonoid components during processing may be key to its enhanced anti-inflammatory effects.

Ischemia-reperfusion injury (IRI) can lead to organ dysfunction and tissue necrosis in the liver, kidney, myocardium and spinal cord, and there is currently a lack of effective treatment options. Human umbilical cord mesenchymal stem cell (HUC-MSC) and their derivatives have anti-inflammatory, anti-apoptotic, reactive oxygen species scavenging, mitochondrial and endothelial function improvement properties, and are ideal gene therapy carrier cells, providing new possibilities for the treatment of IRI in different organs. This article reviews the concept and mechanisms of IRI, the biological characteristics of HUC-MSC and their derivatives and their comparison with mesenchymal stem cells from other sources, and the mechanisms of HUC-MSC in treating IRI in different organs. It also summarizes and analyzes the advantages and disadvantages of HUC-MSC in protecting different organs from IRI, and prospects future research directions to explore more valuable research paths.

Objective To analyze the spatial and temporal distribution characteristics of hand-foot-mouth disease (HFMD) in Zibo City, to explore the key incidence areas, and to find a suitable prediction model, so as to provide reference for the prevention and control of HFMD. Methods The spatiotemporal clustering characteristics of HFMD in Zibo City from 2018 to 2023 were analyzed by using SaTScan 10.0.2 software and ArcGIS 10.7 software. A combination model of ARIMA and SVM was established, and the prediction results were verified and compared. Results Spatial clustering analysis showed that there was spatial clustering of the incidence of HFMD in various townships of Zibo City from 2020 to 2022. The high-high clustering areas and Getis-Ord hot spot areas were mainly concentrated in some main urban areas of Zhangdian District, Zichuan District, and Huantai County. A total of 2-5 aggregation areas were detected by spatiotemporal scanning analysis. The first-type aggregation areas were mainly concentrated in the towns of Zhangdian District, Huantai County, Linzi District, Zhoucun District and Gaoxin District. The aggregation months were July, August, September and November. The model prediction results showed that the ARIMA-SVM combined model was more accurate than the traditional ARIMA model. Conclusion There is a spatiotemporal clustering of hand-foot-mouth disease in Zibo City. The ARIMA-SVM combined model can be used to predict the incidence of hand-foot-mouth disease in Zibo City, and to strengthen health education and disease monitoring in high-risk areas and populations during the epidemic months.

OBJECTIVE: To explore the effects and mechanisms of the C-X-C motif chemokine ligand 12/C-X-C motif chemokine receptor 4 (CXCL12/CXCR4) signaling axis on apoptosis and autophagy in SH-SY5Y neuronal cells subjected to oxygen-glucose deprivation/reperfusion (OGD/R) model in vitro. METHODS: SH-SY5Y cells were divided into the following groups: OGD/R group and non-OGD/R group, with the OGD/R group subjected to OGD/R modeling and the non-OGD/R group receiving no treatment. Cells were also divided into CXCL12⁺ and CXCL12^- groups; the CXCL12⁺ group received 0.1 mg/L exogenous recombinant CXCL12 (rhCXCL12) at reoxygenation, while the CXCL12^- group did not. Another set of cells was divided into CXCL12+AMD3100 and CXCL12 groups; the CXCL12+AMD3100 group was pretreated with 2.5 mg/L AMD3100, a CXCR4 inhibitor, for 2 hours before OGD/R and received both 2.5 mg/L AMD3100 and 0.1 mg/L rhCXCL12 at reoxygenation, whereas the CXCL12 group received rhCXCL12 only. Additionally, cells were divided into small interfering RNA CXCR4 (siCXCR4) and small interfering RNA negative control (siNC) groups; the siCXCR4 group underwent CXCR4 knockdown before OGD/R modeling and received 0.1 mg/L rhCXCL12 at reoxygenation, while the siNC group, transfected with a negative control, received the same treatment. Protein expression of autophagy-related 16 (ATG16), microtubule-associated protein 1 light chain 3 (LC3), aquaporin-3 (AQP3), and CXCR4 was detected by Western blotting. Apoptosis rate and CXCR4 expression were measured by flow cytometry. RESULTS: Compared with the non-OGD/R group, the OGD/R group showed a significantly increased apoptosis rate and markedly decreased protein expression levels of ATG16, LC3, AQP3, and CXCR4 (all P < 0.05). CXCR4 fluorescent expression was also significantly reduced, suggesting that OGD/R simultaneously affects neuronal apoptosis and autophagy while inhibiting CXCR4 and AQP3 expression in SH-SY5Y cells. Compared with the CXCL12^- group, the CXCL12⁺ group exhibited no significant change in apoptosis rate but demonstrated significantly increased protein expression of ATG16, LC3, and AQP3 (ATG16/GAPDH: 1.21±0.10 vs. 1.00±0.00; LC3/β-actin: 1.22±0.10 vs. 1.00±0.00; AQP3/β-actin: 1.26±0.04 vs. 1.00±0.00; all P < 0.05). CXCR4 expression was also significantly enhanced (fluorescence intensity: 1.19±0.05 vs. 1.00±0.00, P < 0.05), indicating that CXCL12 may promote autophagy in OGD/R-injured SH-SY5Y cells via the CXCR4/AQP3 pathway. Compared with the CXCL12 group, the CXCL12+AMD3100 group showed no significant difference in apoptosis rate but significantly lower protein levels of ATG16 and LC3 (ATG16/GAPDH: 0.75±0.08 vs. 1.00±0.00; LC3/GAPDH: 0.86±0.07 vs. 1.00±0.00; both P < 0.05), suggesting that CXCL12 induces autophagy in OGD/R SH-SY5Y cells through CXCR4. Compared with the siNC group, the siCXCR4 group showed no significant change in apoptosis rate but significantly reduced protein expression of ATG16, LC3, AQP3, and CXCR4 (ATG16/GAPDH: 0.76±0.06 vs. 1.00±0.00; LC3/GAPDH: 0.79±0.11 vs. 1.00±0.00; AQP3/GAPDH: 0.81±0.05 vs. 1.00±0.00; CXCR4/GAPDH: 0.86±0.04 vs. 1.00±0.00; all P < 0.05), indicating that CXCR4 knockdown suppresses OGD/R-induced autophagy in SH-SY5Y cells likely via AQP3. CONCLUSIONS The CXCL12/CXCR4 signaling axis can regulate OGD/R-induced autophagy in SH-SY5Y cells through AQP3 without affecting apoptosis, indicating a role for this pathway in neuronal autophagy during cerebral ischemia/reperfusion injury.
Humans ; Receptors, CXCR4/metabolism* ; Chemokine CXCL12/metabolism* ; Autophagy ; Glucose/metabolism* ; Apoptosis ; Neurons/cytology* ; Oxygen/metabolism* ; Signal Transduction ; Cell Line, Tumor ; Cell Hypoxia ; Benzylamines ; Cyclams

Charcot-Marie-Tooth disease (CMT) is a progressive hereditary peripheral neuropathy characterized by symmetrical distal muscle atrophy, sensory impairment, disappearance of tendon reflexes in both lower limbs, arch foot, claw hand, and scoliosis. This article reports a family of CMT type 4C (CMT4C), whose proband carries a compound heterozygous mutation of c.2782C>T and c.1586G>A in the SH3TC2 gene, with ataxia as the main symptom. The literatures related to CMT4C patients in major databases at home and abroad are summarized to provide reference for early identification and diagnosis of this type of patient.

The rationale for the design of control groups in tuina clinical trial is the foundation for rigorously validating the effectiveness and safety of this therapy. This article reviewed the current state of the design of tuina placebo in control groups of clinical trials， pointed out the necessity of setting up tuina placebo in clinical trials of tuina， analyzed the challenges in implementing blinding of tuina manipulation， and concluded that tuina placebo is still challenged by the placebo effect， the diversification of tuina manipulation but the lack of standardization， and the difficulty of implementing blinding due to the high level of public awareness of tuina. This article also summarized the design of placebo manipulation in three types of clinical trials， including spinal manipulation， acupressure， and paediatric tuina， and proposed four strategies for designing placebo tuina manipulation-controlling placebo effects， developing operational standards for placebo tuina manipulation， ensuring the rigor of blinding implementation， and applying new technologies to enhance the standardization and blinding capacity of placebo tuina methods. So the article is aimed at improving the methodological quality of tuina clinical trial designs， and promoting the standardization and scientificity of tuina clinical trial design.

Objective To evaluate the transition rules of normal body mass index(BMI),overweight and metabolic syndrome(MetS)in patients with major depressive disorder(MDD).Methods Patients with MDD who had multiple admission records between Jan 2016 and Nov 2021 in Beijing Anding Hospital,Capital Medical University were included.Based on the overweight and metabolic syndrome status assessed at each admission,the patients were categorized into three states:normal BMI,overweight and metabolic syndrome.A multi-state Markov model was used to analyze the transition intensity and transition frequency between three states and the influence of covariates on transitions.Results A total of 892 records of 398 subjects were included,with a median age of 56 years old and 31.4% males.The median follow-up period was 40 months.The multi-state model showed that there were 494 transitions between the three states,of which 5.1% moved from normal BMI to overweight and 5.5% moved from overweight to MetS.The intensity of transition was the highest from overweight to MetS,9.52 times greater than overweight to normal BMI.After 48.53 months,MDD patients with normal BMI began to transition to MetS.For overweight MDD patients,the transition to MetS started after 8.77 months.MDD patients with normal BMI or overweight had 31.4% and 50.4% probabilities of developing Mets after 36 months.For MDD patients comorbid with MetS,the probability of staying at MetS was 51.2% after 36 months.Multivariate analysis showed that being unmarried was a risk factor against developing overweight in normal BMI MDD patients,while a higher level of education was a protective factor against developing MetS in overweight MDD patients.Conclusion MDD patients exhibited a higher intensity and risk of developing MetS,and it is not easy to reverse MetS,suggesting that BMI management and MetS intervention should be strengthened in MDD patients.

Objective:To determine the optimal threshold for trigger-day progesterone levels in gonadotropin-releasing hormone (GnRH) antagonist protocols.Methods:A cohort study was performed. The clinical data were retrospectively analyzed from patients who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) for assisted reproduction at the Reproductive Medicine Center of Tianjin Central Obstetrics and Gynecology Hospital between January 2014 and May 2023. The study included 5 760 fresh transfer cycles where the female partner had undergone ovarian stimulation using a GnRH antagonist protocol. This was a single-arm study. The primary outcome measures were clinical pregnancy rate and live birth rate. The association between progesterone level on the trigger day and clinical pregnancy outcome and the dose-response relationship were analyzed by restricted cubic spline. Results:The progesterone level on the day of human chorionic gonadotropin trigger was (1.33±0.38) μg/L. Among the included cycles, 2 900 cycles underwent conventional IVF fertilization, while 2 860 cycles underwent ICSI. The biochemical pregnancy rate was 44.79% (2 580/5 760), the clinical pregnancy rate was 40.35% (2 324/5 760), and the live birth rate was 31.46% (1 812/5 760). Progesterone levels on the trigger day in GnRH antagonist protocols showed a nonlinear association with both clinical pregnancy rate and live birth rate (both P<0.001). When progesterone levels were below 0.61 μg/L, the clinical pregnancy rate increased with rising progesterone levels, but decreased significantly once this threshold was exceeded. Similarly, the live birth rate increased with progesterone levels below 0.63 μg/L and declined beyond that point. Conclusion:Progesterone levels on the optimal trigger day for achieving the highest clinical pregnancy rate and live birth rate in GnRH antagonist protocols are peak values of 0.61 μg/L and 0.63 μg/L, respectively. Using these thresholds, the impact of progesterone levels on the trigger day shows a positive effect on both clinical pregnancy rate and live birth rate up to these points, after which the effects become negative.

Mild cognitive impairment(MCI)is a clinical condition that lies between normal aging and dementia and can be considered as the initial stage of dementia development.Executive dysfunction is one of the core symptoms of dementia, the maintenance and improvement of executive function play a central role in delaying the onset of dementia.At present, many studies have shown that cognitive training can improve executive function in MCI patients, but there are few researches and no consensus on the underlying mechanisms.This paper provides a review of the effects of cognitive training on executive function in patients with MCI, explores the impact of executive function deficits and cognitive training on the behavioral and neural levels of executive function in patients with MCI, and points out the limitations of current MCI intervention strategies and potential development directions, with the aim of providing new insights into the intervention and treatment of MCI.