ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

Objective:To investigate clinical characteristics, treatment approaches, and prognosis of drug-induced hypersensitivity syndrome (DIHS) in children.Methods:A retrospective analysis was performed on clinical data from pediatric inpatients with DIHS in Department of Dermatology, Beijing Children's Hospital from 2009 to 2023. The clinical data included demographic characteristics, clinical manifestations, laboratory findings, treatment regimens, and outcomes.Results:A total of 103 children with DIHS were included, comprising 54 males (52.4%) and 49 females (47.6%), with ages ( M [ Q1, Q3]) of 2.3 (1.2, 4.5) years. Primary causative drugs were antibiotics (52 cases, 45.2%), antiepileptic drugs (41 cases, 35.7%), and nonsteroidal anti-inflammatory drugs (19 cases, 16.5%), with a median latency period of 12 days. All patients presented with rashes, including 72 (69.9%) with maculopapular rashes, 69 (67.0%) with edema (including 46 with facial edema). Lip involvement occurred in 25 cases (24.3%), and mucosal involvement was noted in 11 cases (10.7%). Additionally, 102 (99.0%) patients had fever, and 79 (76.7%) presented with lymphadenectasis. Eosinophilia was present in 64 cases (62.1%). Among 84 patients tested for atypical lymphocytes, 51 (60.7%) showed elevated percentages of atypical lymphocytes. Liver involvement was noted in 94 cases (91.3%), followed by pulmonary involvement in 31 (30.1%), gastrointestinal symptoms in 25 (24.3%), cardiac involvement in 14 (13.6%), renal involvement in 10 (9.7%), and pancreatic involvement in 7 cases (6.8%). Among 82 patients tested for blood immunocytes, 49 (59.8%) showed decreased percentages of B lymphocytes, and 69 (84.1%) showed decreased percentages of natural killer cells. Of 88 patients tested for serum immunoglobulins, 40 (45.5%) showed decreased IgA levels. Among 20 patients tested for serum cytokines, 15 (75.0%), 15 (75.0%), 13 (65.0%), and 12 (60.0%) showed elevated levels of interleukin (IL) -5, IL-6, IL-10, and interferon-γ, respectively. All patients received systemic glucocorticoid therapy, among whom 86 additionally received intravenous immunoglobulin therapy, 4 received Janus kinase inhibitors, and 3 received dupilumab. Five patients died, 9 developed hemophagocytic lymphohistiocytosis, 6 developed bronchiolitis obliterans, and 5 experienced long-term immune-related sequelae. Conclusions:Among these children with DIHS, antibiotics were the most common causative drugs, and the latency period could be shorter than 2 weeks. In addition to the common involvement of the liver and lungs, gastrointestinal and cardiac impairments were relatively frequent, while renal involvement was rare. Immunological features included decreased percentages of B lymphocytes and natural killer cells, reduced IgA levels, and elevated levels of cytokines such as IL-5, IL-6, IL-10, and interferon-γ.

This study was aimed at investigating infections with Giardia and Cryptosporidium in Ochotona curzoniae in Zoige County,Sichuan Province.O.curzoniae were captured in five townships of Zoige County(Dazhasi,Axi,Hongxing,Tangke,and Maixi)between March and December of 2023.DNA from the gastrointestinal contents was subjected to nested PCR to amplify Giardia bg,gdh,and tpi genes,and the Cryptosporidium SSU rRNA gene.The sequences of PCR-PCR products were analyzed and compared.Phylogenetic trees were constructed to determine the protozoa species and genotypes.A total of 114 O.curzoniae animals were captured,among which 44 samples showed bg gene positivity,and 14 samples showed gdh gene positivity for Giardia.The total detection rate was 43.9％(50/114),and two assemblages were detected(assem-blage E and a new assemblage tentatively termed assemblage OC1);the positivity rate for Cryptosporidium was 7.0％(8/114),and three new genotypes were observed.Mixed infection with Cryptosporidium and Giardia was present in some sam-ples,with a detection rate of 3.5％(4/114).Giardia lamblia and Giardia sp.(REG-1,REG-2)were prevalent in O.curzoni-ae in Zoige County in Sichuan province;assemblage E was the dominant assemblage,and the new assemblage OC1 was pres-ent;and Cryptosporidium sp.(REG-1,REG-2,and REG-3)were identified.In summary,future monitoring of Giardia and Cryptosporidium should be further strengthened in Zoige to provide detailed data for promoting local public health.

This study aimed to explore the molecular mechanism of rubioncolin C(RuC) in inhibiting gastric cancer(GC). AGS and MGC803 cell lines were selected as cellular models. After treating the cells with RuC at different concentrations, the effects of RuC on the proliferation ability of GC cells were assessed using the CCK-8 method, real-time cellular analysis(RTCA), and colony formation assays. Transmission electron microscopy was used to observe subcellular structural changes. Immunofluorescence was applied to detect LC3 fluorescent foci. Acridine orange staining was used to evaluate the state of intracellular lysosomes. Western blot was employed to detect the expression of autophagy-related proteins LC3Ⅱ, P62, and lysosomal cathepsin D(CTSD). The SuperPred online tool was used to predict the target proteins that bound to RuC, and molecular docking analysis was conducted to identify the interaction sites between RuC and CTSD. The drug affinity responsive target stability(DARTS) assay was performed to detect the direct binding interaction between RuC and CTSD. The results showed that RuC significantly inhibited the proliferation and colony formation of GC cells at low concentrations, with 24-hour half-maximal inhibitory concentrations(IC_(50)) of 3.422 and 2.697 μmol·L~(-1) for AGS and MGC803 cells, respectively. After 24 hours of treatment with RuC at concentrations of 1, 2, and 3 μmol·L~(-1), the colony formation rates for AGS cells were 61.0%±1.5%, 28.0%±0.5%, and 18.2%±0.5%, respectively, while the rates for MGC803 cells were 56.0%±0.5%, 23.3%±1.0%, and 11.8%±1.0%, all of which were significantly reduced. Transmission electron microscopy revealed that RuC promoted an increase in autophagosome formation in GC cells. Immunofluorescence detection showed that LC3 fluorescent foci of GC cells increased with the increase in RuC dose. RuC up-regulated the expression of autophagy-related proteins LC3Ⅱ and P62 in GC cells. Acridine orange staining indicated that RuC altered the acidic environment of lysosomes. SuperPred online prediction identified CTSD as a potential target protein of RuC. Western blot analysis revealed that RuC induced the up-regulation of the inactive precursor of CTSD in GC cells. CTSD activity assays indicated that RuC reduced the activity of CTSD. Molecular docking simulations found that RuC bound to the substrate-binding region of CTSD, forming hydrogen bonds with the Tyr205 and Asp231 residues. Microscale thermophoresis and DARTS assays further confirmed that RuC directly bound to CTSD. In summary, RuC inhibits lysosomal activity by targeting and down-regulating the expression of CTSD, thereby inducing autophagosome accumulation in GC cells.
Humans ; Stomach Neoplasms/enzymology* ; Cathepsin D/chemistry* ; Cell Line, Tumor ; Molecular Docking Simulation ; Cell Proliferation/drug effects* ; Autophagosomes/metabolism* ; Autophagy/drug effects*

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

Objective:To investigate clinical characteristics, treatment approaches, and prognosis of drug-induced hypersensitivity syndrome (DIHS) in children.Methods:A retrospective analysis was performed on clinical data from pediatric inpatients with DIHS in Department of Dermatology, Beijing Children's Hospital from 2009 to 2023. The clinical data included demographic characteristics, clinical manifestations, laboratory findings, treatment regimens, and outcomes.Results:A total of 103 children with DIHS were included, comprising 54 males (52.4%) and 49 females (47.6%), with ages ( M [ Q1, Q3]) of 2.3 (1.2, 4.5) years. Primary causative drugs were antibiotics (52 cases, 45.2%), antiepileptic drugs (41 cases, 35.7%), and nonsteroidal anti-inflammatory drugs (19 cases, 16.5%), with a median latency period of 12 days. All patients presented with rashes, including 72 (69.9%) with maculopapular rashes, 69 (67.0%) with edema (including 46 with facial edema). Lip involvement occurred in 25 cases (24.3%), and mucosal involvement was noted in 11 cases (10.7%). Additionally, 102 (99.0%) patients had fever, and 79 (76.7%) presented with lymphadenectasis. Eosinophilia was present in 64 cases (62.1%). Among 84 patients tested for atypical lymphocytes, 51 (60.7%) showed elevated percentages of atypical lymphocytes. Liver involvement was noted in 94 cases (91.3%), followed by pulmonary involvement in 31 (30.1%), gastrointestinal symptoms in 25 (24.3%), cardiac involvement in 14 (13.6%), renal involvement in 10 (9.7%), and pancreatic involvement in 7 cases (6.8%). Among 82 patients tested for blood immunocytes, 49 (59.8%) showed decreased percentages of B lymphocytes, and 69 (84.1%) showed decreased percentages of natural killer cells. Of 88 patients tested for serum immunoglobulins, 40 (45.5%) showed decreased IgA levels. Among 20 patients tested for serum cytokines, 15 (75.0%), 15 (75.0%), 13 (65.0%), and 12 (60.0%) showed elevated levels of interleukin (IL) -5, IL-6, IL-10, and interferon-γ, respectively. All patients received systemic glucocorticoid therapy, among whom 86 additionally received intravenous immunoglobulin therapy, 4 received Janus kinase inhibitors, and 3 received dupilumab. Five patients died, 9 developed hemophagocytic lymphohistiocytosis, 6 developed bronchiolitis obliterans, and 5 experienced long-term immune-related sequelae. Conclusions:Among these children with DIHS, antibiotics were the most common causative drugs, and the latency period could be shorter than 2 weeks. In addition to the common involvement of the liver and lungs, gastrointestinal and cardiac impairments were relatively frequent, while renal involvement was rare. Immunological features included decreased percentages of B lymphocytes and natural killer cells, reduced IgA levels, and elevated levels of cytokines such as IL-5, IL-6, IL-10, and interferon-γ.