ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objective: Negative symptoms in schizophrenia indicate a poor prognosis. However, the mechanisms underlying the development of negative symptoms remain unclear. This study investigated the relationship between negative symptoms in schizophrenia and frontal alpha asymmetry (FAA). Methods: The study used a 32-channel electroencephalography to acquire alpha power in 4 target-paired sites in each patient. Regional alpha asymmetry was calculated based on the alpha power using EEGLAB Frontal Alpha Asymmetry Toolbox. Results: Sixty schizophrenia patients with predominant negative symptoms (PNS), 72 stabilized schizophrenia (SS) patients, and 73 healthy control (HC) participants were enrolled in this study. No significant differences were observed in FAA between the PNS and SS groups, although both groups exhibited reduced P3-P4 alpha asymmetry compared to HCs. A positive correlation was found between F7-F8 alpha asymmetry and illness duration. Additionally, a predictive model based on P3-P4 alpha asymmetry scores was able to differentiate schizophrenia patients from HCs, achieving a sensitivity of 71.2% and a specificity of 72.6%. Conclusion This study highlighted that parietal alpha asymmetry could serve as a valuable diagnostic tool for schizophrenia.

Objective: This study aimed to explore the relationships between various exercise components (frequency, intensity, duration) and social anxiety. Methods: A sample of 844 college students in China participated in this study. The Physical Activity Rating Scale-3 assessed participants’ daily physical activity. Social anxiety levels were measured using the Liebowitz Social Anxiety Scale. A questionnaire was developed to collect demographic information and examine the relationships between exercise components and social anxiety levels. Results: One-way analysis of variance revealed significant differences in social anxiety levels across varying physical activity intensities. Specifically, students engaging in high levels of physical activity exhibited the lowest social anxiety. Post hoc analyses identified that exercise frequency F3 (p<0.01), exercise duration D5 (p<0.01), and exercise intensity I3 (p<0.01) were significantly associated with the lowest social anxiety levels. Among these components, regression analysis indicated that exercise duration (p<0.01) had the most substantial impact on social anxiety levels, followed by exercise frequency (p<0.05). In contrast, exercise intensity (p>0.05) did not significantly affect social anxiety levels. Conclusion The most influential factors associated with decreased social anxiety were: 1) moderate to high exercise intensity, 2) exercise duration of at least one hour, and 3) exercise frequency of at least 1–2 times per week. Among these factors, exercise duration and frequency demonstrated significantly stronger associations with reduced social anxiety. Therefore, it is advisable to prioritize exercise duration and frequency in physical activity programs for college students to reduce social anxiety and achieve more substantial outcomes.

BACKGROUND:The composite hydrogel scaffold formed by crosslinking of gelatin-methacryloyl(Gel-MA)and treated dentin matrix(TDM)under a certain proportion of ultraviolet light has good porosity,mechanical properties,swelling properties,and biodegradation rate,which provides a new idea and method for clinical pulp regeneration of young permanent teeth. OBJECTIVE:To explore the effect of Gel-MA/TDM composite hydrogel scaffold with 1:2 mass ratio on the proliferation ability and osteogenic/odontoblast differentiation ability of human dental pulp stem cells. METHODS:The passage 3 dental pulp stem cells were inoculated into the Gel-MA/TDM composite hydrogel scaffold with a mass ratio of 1:2.The proliferation ability of human dental pulp stem cells in the composite hydrogel scaffold was detected by CCK-8 assay.Dental pulp stem cells at passage 3 were cultured in Gel-MA/TDM composite hydrogel scaffold with a mass ratio of 1:2 for osteogenic induction.The formation of mineralized nodules was observed by alkaline phosphatase and alizarin red staining.The gene expression levels of odontogenic factors(dentin matrix protein 1,dentin sialophosphoprotein),and osteogenic factors(osteocalcin,Runt-related transcription factor 2)were detected by RT-PCR. RESULTS AND CONCLUSION:(1)The results of CCK-8 assay showed that the proliferation ability of dental pulp stem cells increased significantly in the first 7 days,and slowed down on day 10.(2)The results of alkaline phosphatase staining and alizarin red staining showed that the alkaline phosphatase activity and the formation of mineralized nodules of dental pulp stem cells in the Gel-MA/TDM composite hydrogel group were stronger than those in Gel-MA hydrogel group(P<0.05).(3)RT-PCR results showed that the gene expression levels of dentin matrix protein 1,dentin sialophosphoprotein,osteocalcin,and Runt-related transcription factor 2 in dental pulp stem cells in Gel-MA/TDM composite hydrogel group were significantly higher than those in Gel-MA hydrogel group(P<0.05).The gene expression level at 14 days was significantly higher than that at 7 days(P<0.05).The results conclude that the dental pulp stem cells cultured on Gel-MA/TDM composite hydrogel scaffolds with a mass ratio of 1:2 exhibit a good proliferation ability,which can strengthen the osteogenic and odontogenic differentiation abilities of dental pulp stem cells.

Objective To elucidate the causal relationships between colorectal cancer (CRC) and prevalent psychiatric disorders through a two-sample Mendelian randomization approach. Methods Utilizing publicly available genome-wide association study data, we explored the connections between CRC and various psychiatric disorders, including depression, anxiety, bipolar disorder, and schizophrenia. We applied three statistical analyses: inverse variance weighting, MR-Egger, and median weighting. Sensitivity analyses were conducted to ensure the reliability and validity of the results. Results Inverse variance weighting analysis showed no significant links between CRC and depression (P=0.090), anxiety (P=0.099), or schizophrenia (P=0.899). Conversely, a significant inverse relationship was found with bipolar disorder (P=0.010). Conclusion No causal connection exists between CRC and the psychiatric conditions of depression, anxiety, or schizophrenia. However, CRC may have a causal association with a reduced risk of bipolar disorder, further supporting the existence of the gut-brain axis.

OBJECTIVE To build a Tibetan-language medication service platform based on “internet+” and evaluate its effect on improving medication compliance and safety of Tibetan patients with chronic disease. METHODS Medication guidance contents of commonly used drugs in the outpatient department were summarized， translated and recorded in Tibetan-language or video to form a “text-audio-video” multi-dimensional “internet+ ” Tibetan-language medication service platform. A total of 387 Tibetan outpatients with chronic disease in our hospital after the implementation of “internet+” Tibetan-language medication service platform （from January 2024 to June 2024） in our hospital were selected as the intervention group， and 387 Tibetan outpatients before the implementation （from January 2023 to June 2023） were selected as the control group. Patients in the control group received conventional window-based Chinese-language medication services， while patients in the intervention group received both conventional window-based Chinese-language medication service and “internet+ ” Tibetan-language medication service. The medication compliance of patients was evaluated using the 12-item Medication Compliance Scale. A six-level causality assessment was conducted as the principles for analyzing adverse drug reactions （ADR） set by the National Center for ADR Monitoring. Additionally， statistics were compiled on the occurrence of ADR that were assessed as “definite”“probable” or “possible” in the causality assessment. RESULTS The proportion （31.0%） of patients with good medication compliance and compliance scores [39.0 （37.0，42.0）] of patients in the intervention group were significantly better than control group [7.0%， 21.0（19.0， 23.0）]（ P＜0.05）. There were no statistically significant differences in the incidence of various types of ADR or the overall incidence between the two groups （P＞0.05）. CONCLUSIONS The “internet+” Tibetan-language medication service platform is constructed successfully； the service can effectively improve the medication compliance of Tibetan-language patients， but its effect on improving the medication safety of patients is limited.

The red doctor culture runs through the development process of China’s red health undertakings. It is a unity of revolutionary culture， health culture， and educational culture， providing rich educational resources for ideological and political education in medical colleges and universities. From the perspective of historical logic， red doctor culture is rooted in the traditional medical ethics thought of “medicine is the art of benevolence” in ancient China， as well as has evolved alongside the century-long development of the health and well-being undertakings led by the Communist Party of China. From the perspective of theoretical logic， red doctor culture is closely related to Xi Jinping Thought on Culture， the principle of the dialectical relationship between social existence and social consciousness， and the theory of cultural leadership. From the perspective of practical logic， it is necessary to clarify the practical path from three aspects， namely accurately grasping the Marxist theoretical foundation of the red doctor culture and highlighting its orientation of the ideological and political education of medical students； making effective use of existing resources of red doctor culture to improve the content of ideological and political education and consolidate the foundation of red doctor literacy； optimizing the construction of teaching teams for ideological and political theory courses in medical colleges and universities. From the perspective of value orientation， the red doctor culture is conducive to cultivating the professional ethics spirit of medical students， meeting the teaching needs of ideological and political theory courses in medical colleges and universities， and assisting the construction of the healthy China initiative.

Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68⁺ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.