ObjectiveTo investigate the mechanisms by which Jianpi Yangzheng Xiaozheng prescription （JPYZXZ） treats poorly cohesive gastric carcinoma （PC-GC） through regulation of ubiquitin-specific peptidase 51 （USP51）. MethodsIn vitro experiments： Cell viability and proliferation of PC-GC cell lines （MKN-45 and HGC-27） treated with different concentrations of JPYZXZ （2， 4， 6 g·L^-1） were assessed using Cell Counting Kit-8 （CCK-8） and colony formation assays. Cell migration was evaluated by wound healing （scratch） and Transwell assays. The mRNA and protein expression levels of USP51， zinc finger E-box-binding homeobox 1 （ZEB1）， and epithelial-mesenchymal transition （EMT）-related markers （e.g.， E-cadherin） were detected by quantitative real-time PCR （Real-time PCR） and Western blot， respectively. Subsequently， stable MKN-45 and HGC-27 cell lines with USP51 knockdown （sh-USP51） and overexpression （oe-USP51） were constructed. Their migration ability and EMT-related protein expression were further evaluated by scratch assay， Transwell assay， and Western blot. In vivo experiments： A subcutaneous xenograft model of MKN-45 human gastric cancer was established in BALB/c nude mice. Thirty mice were randomly divided into six groups （NC， NC + JPYZXZ， sh-USP51， sh-USP51 + JPYZXZ， oe-USP51， and oe-USP51 + JPYZXZ）， with five mice in each group. After successful modeling， mice in the treatment groups were administered JPYZXZ （30 g·kg^-1） by gavage for 28 days. Body weight and tumor volume were monitored during the experiment. The expression levels of USP51 and EMT-related proteins in tumor tissues were detected by Western blot and immunohistochemistry （IHC）. ResultsCompared with the blank group， the colony formation rate， wound healing rate， and number of migrated cells in MKN-45 and HGC-27 cells were significantly reduced in all JPYZXZ groups and the 5-fluorouracil （5-FU） group （P<0.05）. The mRNA and protein expression levels of USP51 were decreased （P<0.05）. The expression of ZEB1 and mesenchymal phenotype proteins （e.g.， N-cadherin and vimentin） was reduced （P<0.05）， whereas the expression of the epithelial marker E-cadherin was increased （P<0.05）. Compared with the control group， USP51 expression was decreased in the sh-USP51 group and increased in the oe-USP51 group （P<0.05）. Compared with the NC group， USP51 knockdown significantly reduced the migration and proliferation of gastric cancer cells （P<0.01）， decreased the expression of ZEB1 and EMT-related proteins， and increased E-cadherin expression （P<0.05）. In vivo results showed that JPYZXZ significantly inhibited the growth of xenograft tumors in nude mice （P<0.05） and markedly reversed the abnormal expression of EMT-related proteins in tumor tissues （P<0.05）. ConclusionThe therapeutic mechanisms of JPYZXZ in PC-GC may be associated with inhibition of the EMT process via regulation of the USP51-ZEB1 signaling pathway.

Objective: To explore the efficacy of a novel injectable hydrogel (GelMA/P11/IL4@LIP) loaded with P11 bacteriophages and interleukin-4 (IL-4) liposomes (LIP) in preventing relapse after maxillary expansion in mice, providing experimental evidence for its clinical application. Methods: This study was approved by the experimental animal ethics committee of our hospital. First, 15 7-week-old C57BL/6 mice were used to establish a maxillary expansion model and divided into 5 groups (3 mice in each group): a control group, post expansion day 3 group (PED3 group), post expansion day 7 group (PED7 group), retention for 14 days group (RET group), and relapse for 7 days group (REL group). The mice in each group were sacrificed at their designated time points (day 0, 3, 7, 21, 28), and their maxilla and anterior cranial regions were collected. Bone parameters and the inter-crestal distance (ICD) of maxillary incisor mesial alveolar ridge were measured using micro-computed tomography (micro-CT). Histological staining was performed to evaluate bone formation and resorption, while immunohistochemistry (IHC) was performed for macrophage markers (CD86 and CD206), mesenchymal stem cell markers (glioma-associated oncogene homolog 1 [Gli1]), and osteogenic markers (Runt-related transcription factor 2 [Runx2] and Osterix [OSX]). Next, GelMA/P11/IL4@LIP was synthesized and administered to mouse models of maxillary expansion. A total of 24 7-week-old C57BL/6 mice were divided into 4 groups (6 mice in each group): a blank control group, GelMA group, GelMA/P11 group, and GelMA/P11/IL4@LIP group. All mice underwent palatal expansion. On PED7, the expanders of all 24 mice were cemented with resin to initiate the 14-day retention period. On day 1 of the retention phase, the mice in each group received injections of saline, GelMA, GelMA/P11, or GelMA/P11/IL4@LIP at the midpalatal suture. After the 14-day retention period, three mice in each group were randomly selected and sacrificed, while the other three had their expanders removed and underwent a 7-day relapse before being sacrificed on day 28 (REL). Micro-CT, histological staining, and IHC were performed to evaluate the preventive effect of GelMA/P11/IL4@LIP on post-expansion relapse. Results: The mice maxillary expansion model exhibited a decreased ICD at REL compared to RET in micro-CT analysis (P = 0.008). IHC analysis demonstrated prolonged M1 macrophage infiltration, scarce Gli1+ mesenchymal stem cells, and insufficient expression of osteogenic markers (RUNX2 and OSX) (P < 0.001). Compared to the blank control and GelMA groups, GelMA/P11/IL4@LIP hydrogel injection in the midpalatal suture led to increased ICD at REL, promoted the timely M2 polarization of macrophages, recruited Gli1+ mesenchymal stem cells, and upregulated the expression of RUNX2 and OSX (P < 0.05). Conclusion The mechanism of relapse after maxillary expansion involves the persistent infiltration of M1 macrophages, as well as the inadequate recruitment and insufficient osteogenic differentiation of MSCs in the midpalatal suture. The GelMA/P11/IL4@LIP composite enhanced orofacial mesenchymal stem cell recruitment and promoted the M2 polarization of macrophages, thereby enhancing osteogenesis in the midpalatal suture and preventing post-expansion relapse.

Objective: This study explored whether anxiety and core self-evaluation mediate the relationship between negative life events and depressive symptoms in adolescents of the Yi ethnic minority in China. Methods: In this cross-sectional study, a convenience sample of 627 Yi adolescents 10–19 years old (252 males, 40.2%) from primary, middle and high schools in Liangshan Prefecture in China completed the Adolescent Self-Rating Life Events Checklist (ASLEC) to report on negative life events, the Second Edition of the Beck Depression Inventory (BDI-II) to report on depressive symptoms, the Core Self-Evaluations Scale (CSES) to describe core self-evaluation, and the Screen for Child Anxiety-Related Emotional Disorders (SCARED) to report anxiety symptoms. Results: In Pearson correlation analysis, total score and dimension subscores on the ASLEC correlated positively with total score and dimension subscores on the SCARED survey as well as with total score on the BDI. Total ASLEC score and dimension subscores correlated negatively with total CSES score. Mediation analysis indicated that negative life events affected depressive symptoms directly, as well as indirectly via core self-evaluation (mediating effect was 0.087; 95% confidence interval [CI], 0.063–0.113; p<0.001). The chain-mediated pathway effect was significant (mediating effect was 0.017; 95% CI, 0.011–0.026; p<0.001). Conclusion Yi adolescents in Liangshan Prefecture show certain prevalence of anxiety and depression, and they score relatively low on core self-evaluation. In this ethnic group, negative life events can affect depressive symptoms directly as well as indirectly through chain-mediated effects of anxiety and core self-evaluation.

OBJECTIVES: The major histocompatibility complex class I chain-related gene A (MICA), a component of the human leukocyte antigen (HLA) gene complex, is involved in the pathogenesis of various diseases including cancers and autoimmune disorders. Rosacea, a chronic inflammatory skin disease with a complex pathogenesis, potentially influenced by genetic and autoimmune factors. This study aims to investigate the relationship among MICA gene polymorphisms, single nucleotide polymorphisms (SNPs), and susceptibility to rosacea, thereby offering new insights into the disease mechanism. METHODS: Peripheral blood DNA samples were collected from 84 patients with rosacea (rosacea group) and 223 healthy volunteers (control group) who visited the Dermatology Outpatient Department of Xiangya Hospital of Central South University between November 2017 and November 2019. MICA genotyping was performed using polymerase chain reaction-sequencing-based typing (PCR-SBT) and the next-generation sequencing (NGS), and the accuracy of the 2 methods was compared. The frequency distributions of MICA alleles between the 2 groups were analyzed. Amino acid clustering and SNP site analyses were conducted to identify haplotype-linked SNPs and to classify MICA polymorphic variants. Distribution differences of these classifications between groups were also examined. RESULTS: Blood tests in rosacea patients showed mildly elevated, with no significant changes in lymphocyte counts. Both PCR-SBT and NGS accurately identified MICA alleles. The most common alleles in the rosacea group were MICA*010:01, MICA*008:04, and MICA*019:01. The frequencies of MICA*002:01 and MICA*027 were significantly lower in the rosacea group compared to controls (6.55% vs 18.16% and 1.19% vs 5.38%, respectively), while and MICA*010:01 were significantly higher (7.74% vs 3.36% and 31.55% vs 18.61%, respectively; all P<0.05). Five short tandem repeat (STR) alleles were identified. Frequencies of MICA-A4 and MICA-A9 were lower in the rosacea group than in the control group (16.07% vs 23.32% and 7.74% vs 17.26%, respectively), whereas MICA-A6 was higher (10.12% vs 4.03%; all P<0.05). Clustering and SNP analysis identified 6 linked SNP sites, classifying MICA variants into Type I (C₃₆+M₁₂₉+K₁₇₃+G₂₀₆+W₂₁₀+S₂₁₅) and Type II (Y₃₆+V₁₂₉+E₁₇₃+S₂₀₆+R₂₁₀+T₂₁₅). Type I MICA variants were significantly associated with rosacea susceptibility. CONCLUSIONS MICA gene polymorphisms are associated with susceptibility to rosacea, and there are 6 linked SNP sites within the MICA gene. Based on this, MICA polymorphic variants are classified into Type I and Type II, with Type I being more closely associated with disease development of rosacea.
Humans ; Polymorphism, Single Nucleotide ; Histocompatibility Antigens Class I/genetics* ; Rosacea/genetics* ; Genetic Predisposition to Disease/genetics* ; Female ; Male ; Adult ; Middle Aged ; Genotype ; Alleles ; Gene Frequency ; Haplotypes ; Case-Control Studies ; Aged ; High-Throughput Nucleotide Sequencing

OBJECTIVES: Managing patients with refractory head and neck cancer pain is one of the more challenging issues in clinical practice, and traditional intrathecal drug delivery also fails to provide adequate analgesia. There are currently no comprehensive and effective treatment methods. This study aims to observe the efficacy and safety of treating intractable head and neck cancer pain with morphine pump via lumbar approach to the prepontine cistern. METHODS: A total of 18 patients with intractable head and neck cancer pain treated with prepontine cistern morphine pumps were selected from the Department of Pain Management, Second Xiangya Hospital, Central South University between September 2019 and July 2023. Statistical analysis was performed on patients' preoperative and postoperative (1 week, 1 month, and 2 months after surgery), Numerical Rating Scale (NRS) scores, Self-Rating Depression Scale (SDS) scores, daily oral morphine consumption, the number of daily breakthrough pain episodes, and postoperative daily intrathecal morphine dosage. RESULTS: The NRS scores, SDS scores, daily oral morphine consumption, and the number of daily breakthrough pain episodes of patients at each time point after surgery were significantly lower than before surgery (all P<0.05). With the gradual increase in the dosage of intrathecal morphine, the daily oral morphine consumption of patients at each postoperative time point was significantly reduced compared to preoperative levels (all P<0.05). The complications related to the operation were mild, including nausea in 5 cases (31.3%), headache in 2 cases (12.5%); hypotension, urine retention, hypersomnia and constipation in 1 case (6.3% each), and no serious adverse events occurred. All improved and were discharged after symptomatic treatment. CONCLUSIONS The implantation of prepontine cistern morphine pump effectively controls intractable head and neck cancer pain, demonstrating characteristics of minimal invasiveness, mild side effects, and low medication dosage under the premise of standardized procedures.
Humans ; Morphine/administration & dosage* ; Male ; Female ; Middle Aged ; Head and Neck Neoplasms/surgery* ; Analgesics, Opioid/administration & dosage* ; Cancer Pain/drug therapy* ; Pain, Intractable/etiology* ; Aged ; Adult ; Infusion Pumps, Implantable ; Pain Management/methods*

Critically ill patients often experience significant skeletal muscle wasting due to prolonged bed rest, metabolic disorders, inflammatory responses and malnutrition, which affects the patient's mobility and may also lead to increased mortality. Timely and accurate assessment of muscle status is important for optimizing treatment strategies and improving patient prognosis. There are various limitations in the current methods of assessing muscle mass, and muscle ultrasound, as a noninvasive, convenient, low-cost and suitable technique for bedside monitoring, has received increasing attention for its application in muscle assessment of critically ill patients. However, there are still a number of challenges in its practical application, such as the lack of uniform standards for the measurement method, the high dependence on the operation, and the reproducibility of the data that needs to be optimized, and so on. The aim of this article is to systematize the research progress of muscle ultrasound in muscle assessment of critically ill patients, and to discuss the advantages and limitations of its clinical application, in order to provide a scientific basis for future research and clinical practice.
Humans ; Critical Illness ; Ultrasonography ; Muscle, Skeletal/diagnostic imaging*

Objective: To investigate the clinical characteristics, the types of unexpected antibodies, and their impacts on immunological risks among patients with different frequencies of cross-matching incompatibility, so as to propose corresponding solutions. Methods: Data of cross-matching incompatibility samples from 92 medical institutions during 2022 to 2024 were collected and divided into three groups based on the frequency of cross-matching. Statistical analysis was performed on disease types, distribution of hematologic diseases, alloantibody detection rates, and proportions of alloantibody types. Results: The 858 patients were divided into three groups based on the frequency of blood cross-matching incompatibility: ≥5 times (8.28%, 71/858), 2 to 4 times (28.21%, 242/858); 1 time (63.52%, 545/858). There was a clustered distribution of disease types in the ≥5 cross-matchings group, with 71.83% (51/71) of patients having tumors or hematologic and hematopoietic diseases. In contrast, the disease types in the 2 to 4 cross-matchings and 1 cross-matching groups were more diverse. An analysis of 249 patients with hematologic diseases found that multiple myeloma was the most common disease in all three groups, accounting for 31.43% (11/35), 35.37% (29/82), and 37.88% (50/132) respectively. In the ≥5 cross-matchings group, myelodysplastic syndrome (14.29%, 5/35) and thalassemia (14.29%, 5/35) were the second most common diseases. In contrast, in the 2 to 4 cross-matchings group and 1 cross-matching group, autoimmune hemolytic anemia was the second most common disease, with prevalence rates of 20.73% (17/82) and 24.24% (32/132), respectively. Alloantibodies were detected in 54.66% of the patients, with antibodies against Rh blood group being most frequent (>50%) in all three groups. The detection rates of alloantibodies/alloantibodies with coexisting autoantibodies decreased across groups: the ≥5 cross-matchings group (70.42%, 50/71) > the 2 to 4 cross-matchings group (54.96%, 133/242) > the 1 cross-matching group (52.48%, 286/545). Conclusion: The risk of alloantibody production increases in patients with multiple cross-matching incompatibilities, especially in those with tumors or hematologic diseases. For handling of cross-matching incompatibility cases, it is recommended to optimize the cross-matching process, implement individualized transfusion plans, and enhance the technical capabilities of clinical transfusion departments and blood group reference laboratories to ensure the safety and effectiveness of transfusions.

Objective: This study explored whether anxiety and core self-evaluation mediate the relationship between negative life events and depressive symptoms in adolescents of the Yi ethnic minority in China. Methods: In this cross-sectional study, a convenience sample of 627 Yi adolescents 10–19 years old (252 males, 40.2%) from primary, middle and high schools in Liangshan Prefecture in China completed the Adolescent Self-Rating Life Events Checklist (ASLEC) to report on negative life events, the Second Edition of the Beck Depression Inventory (BDI-II) to report on depressive symptoms, the Core Self-Evaluations Scale (CSES) to describe core self-evaluation, and the Screen for Child Anxiety-Related Emotional Disorders (SCARED) to report anxiety symptoms. Results: In Pearson correlation analysis, total score and dimension subscores on the ASLEC correlated positively with total score and dimension subscores on the SCARED survey as well as with total score on the BDI. Total ASLEC score and dimension subscores correlated negatively with total CSES score. Mediation analysis indicated that negative life events affected depressive symptoms directly, as well as indirectly via core self-evaluation (mediating effect was 0.087; 95% confidence interval [CI], 0.063–0.113; p<0.001). The chain-mediated pathway effect was significant (mediating effect was 0.017; 95% CI, 0.011–0.026; p<0.001). Conclusion Yi adolescents in Liangshan Prefecture show certain prevalence of anxiety and depression, and they score relatively low on core self-evaluation. In this ethnic group, negative life events can affect depressive symptoms directly as well as indirectly through chain-mediated effects of anxiety and core self-evaluation.

High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

OBJECTIVES: To summarize the clinical manifestations and genetic characteristics of creatine deficiency syndrome (CDS) caused by GAMT gene mutations. METHODS: A retrospective analysis was conducted on the clinical and genetic data of two children diagnosed with GAMT deficiency-type CDS at the Children's Medical Center of Xiangya Hospital, Central South University, from December 2020 to December 2024. RESULTS: The two patients presented with symptoms in infancy, and both had compound heterozygous mutations in the GAMT gene. Case 1 exhibited seizures and intellectual disability, while Case 2 had intellectual disability and attention-deficit hyperactivity disorder. Magnetic resonance spectroscopy of cranial MRI in both patients indicated reduced creatine peaks. After creatine treatment, seizures in Case 1 were controlled, but both patients continued to experience intellectual disabilities and behavioral issues. As of December 2024, a total of 21 cases have been reported in China (including this study), and 115 cases have been reported abroad. All patients exhibited developmental delay or intellectual disabilities, with 66.9% (91/136) experiencing seizures, 33.8% (46/136) presenting with motor disorders, and 36.8% (50/136) having behavioral problems. Seventy-five percent (102/136) of patients received creatine treatment, leading to significant improvements in seizures and motor disorders, although cognitive improvement was not substantial. CONCLUSIONS GAMT deficiency-type CDS is rare and presents with nonspecific clinical features. Timely diagnosis facilitates targeted treatment, which can partially improve prognosis.
Child ; Female ; Humans ; Male ; Creatine/deficiency* ; Guanidinoacetate N-Methyltransferase/deficiency* ; Intellectual Disability/genetics* ; Mutation ; Retrospective Studies ; Rhabdomyolysis/genetics* ; Language Development Disorders ; Movement Disorders/congenital*