BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

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*

OBJECTIVES: To investigate the association between maternal depressive symptoms and adolescent suicidal ideation, and to examine the chain mediating roles of childhood trauma and ineffectiveness. METHODS: A cross-sectional online survey was administered by school psychologists to 4 157 mother-adolescent pairs from middle schools in Shanghai and Henan, China. Measures included the Center for Epidemiological Studies Depression Scale, the Childhood Trauma Questionnaire, and the Children's Depression Inventory. Using Bootstrap method to examine the chain mediating effect of childhood trauma and ineffectiveness on the relationship between maternal depression symptoms and adolescent suicidal ideation. RESULTS: The prevalence of maternal depressive symptoms was 17.68% (735/4 157); among adolescents, the prevalence of depressive symptoms was 15.49% (644/4 157), and suicidal ideation was 28.19% (1 172/4 157). Adolescent depressive symptoms and suicidal ideation were positively correlated with maternal depressive symptoms, childhood trauma, and ineffectiveness (all P<0.01). Childhood trauma significantly mediated the association between maternal and adolescent depressive symptoms (95%CI: 0.046 9-0.077 2). The chain mediation of childhood trauma and ineffectiveness in the association between maternal depressive symptoms and adolescent suicidal ideation was also significant (95%CI: 0.000 7-0.001 3). CONCLUSIONS Higher maternal depressive symptom levels are associated with a greater likelihood of adolescents' exposure to childhood trauma, which increases adolescents' ineffectiveness and, in turn, is associated with suicidal ideation. This chain effect has important implications for social interventions targeting adolescent depression.
Humans ; Suicidal Ideation ; Adolescent ; Female ; Depression/etiology* ; Cross-Sectional Studies ; Mothers/psychology* ; Male ; Child ; Adult

OBJECTIVE: Treating peripheral nerve injury (PNI) presents a clinical challenge due to limited axon regeneration. Strychni Semen, a traditional Chinese medicine, is clinically used for numbness and hemiplegia. However, its role in promoting functional recovery after PNI and the related mechanisms have not yet been systematically studied. METHODS: A mouse model of sciatic nerve crush (SNC) injury was established and the mice received drug treatment via intragastric gavage, followed by behavioral assessments (adhesive removal test, hot-plate test and Von Frey test). Transcriptomic analyses were performed to examine gene expression in the dorsal root ganglia (DRGs) from the third to the sixth lumbar vertebrae, so as to identify the significantly differentially expressed genes. Immunofluorescence staining was used to assess the expression levels of superior cervical ganglia neural-specific 10 protein (SCG10). The ultra-trace protein detection technique was used to evaluate changes in gene expression levels. RESULTS: Strychni Semen and its active compounds (brucine and strychnine) improved functional recovery in mice following SNC injury. Transcriptomic data indicated that Strychni Semen and its active compounds initiated transcriptional reprogramming that impacted cellular morphology and extracellular matrix remodeling in DRGs after SNC, suggesting potential roles in promoting axon regeneration. Imaging data further confirmed that Strychni Semen and its active compounds facilitated axon regrowth in SNC-injured mice. By integrating protein-protein interaction predictions, ultra-trace protein detection, and molecular docking analysis, we identified myeloperoxidase as a potentially critical factor in the axon regenerative effects conferred by Strychni Semen and its active compounds. CONCLUSION Strychni Semen and its active compounds enhance sensory function by promoting axonal regeneration after PNI. These findings establish a foundation for the future applications of Strychni Semen and highlight novel therapeutic strategies and drug targets for axon regeneration. Please cite this article as: Zhang Y, Zhao XY, Liu MT, Zhou ZC, Cheng HB, Jiang XH, Zheng YR, Chen Z. Strychni Semen and its active compounds promote axon regeneration following peripheral nerve injury by suppressing myeloperoxidase in the dorsal root ganglia. J Integr Med. 2025; 23(2): 169-181.
Animals ; Nerve Regeneration/drug effects* ; Mice ; Peripheral Nerve Injuries/physiopathology* ; Male ; Ganglia, Spinal/enzymology* ; Axons/physiology* ; Peroxidase/antagonists & inhibitors* ; Mice, Inbred C57BL ; Drugs, Chinese Herbal/pharmacology* ; Disease Models, Animal ; Strychnine/pharmacology*

Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including ²²³Ra, ⁹⁰Y, Lutetium-177 (¹⁷⁷Lu), ²¹²Pb, and Actinium-225 (²²⁵Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
Humans ; Radiopharmaceuticals/therapeutic use* ; Neoplasms/radiotherapy* ; Radioisotopes/therapeutic use* ; Animals

OBJECTIVE: To investigate the spatiotemporal patterns and socioeconomic factors influencing the incidence of tuberculosis (TB) in the Guangdong Province between 2010 and 2019. METHOD: Spatial and temporal variations in TB incidence were mapped using heat maps and hierarchical clustering. Socioenvironmental influencing factors were evaluated using a Bayesian spatiotemporal conditional autoregressive (ST-CAR) model. RESULTS: Annual incidence of TB in Guangdong decreased from 91.85/100,000 in 2010 to 53.06/100,000 in 2019. Spatial hotspots were found in northeastern Guangdong, particularly in Heyuan, Shanwei, and Shantou, while Shenzhen, Dongguan, and Foshan had the lowest rates in the Pearl River Delta. The ST-CAR model showed that the TB risk was lower with higher per capita Gross Domestic Product (GDP) [Relative Risk ( RR), 0.91; 95% Confidence Interval ( CI): 0.86-0.98], more the ratio of licensed physicians and physician ( RR, 0.94; 95% CI: 0.90-0.98), and higher per capita public expenditure ( RR, 0.94; 95% CI: 0.90-0.97), with a marginal effect of population density ( RR, 0.86; 95% CI: 0.86-1.00). CONCLUSION The incidence of TB in Guangdong varies spatially and temporally. Areas with poor economic conditions and insufficient healthcare resources are at an increased risk of TB infection. Strategies focusing on equitable health resource distribution and economic development are the key to TB control.
Humans ; China/epidemiology* ; Incidence ; Bayes Theorem ; Spatio-Temporal Analysis ; Tuberculosis/epidemiology* ; Socioeconomic Factors

Objective:To investigate the clinical characteristics and prognosis of follicular lymphoma (FL) patients with different primary sites using the Surveillance, Epidemiology, and End Results (SEER) database.Methods:Clinical data of 7167 patients with early-stage FL (stage I-II) from the SEER database between 2000 and 2015 were respectively analyzed. Primary sites were divided into intranodal and extranodal types. Intranodal primary sites included supradiaphragmatic lymph nodes (LN), subphrenic lymph nodes and Waldeyer's ring. Extranodal primary sites consisted of skin, gastrointestinal tract, duodenum, head and neck, other sites. Prognostic factors and overall survival (OS) in patients with different primary sites were analyzed. OS rate was evaluated using Kaplan-Meier method and survival difference between primary sites was compared with log-rank test. Inverse probability treatment weighting (IPTW) and multi-variable analysis were applied to adjust for confounding factors. Multivariate Cox regression analysis of influencing factors of OS was performed.Results:The median age was 63 years old, with the median follow-up time of 63 months. There was no difference in prognosis among the intranodal groups or between the intranodal and extranodal groups. The 10-year OS rates of the supradiaphragmatic lymph LN ( n=2146), subdiaphragmatic LN ( n=2811), and the Waldeyer's ring ( n=151) groups were 70.7%, 69.9% and 73.4%, respectively ( P=0.422 for infradiaphragmatic LN vs. supradiaphragmatic LN, P=1.000 for Waldeyer's ring vs. supradiaphragmatic LN), and 70.3% and 68.9% for intranodal ( n=5108) and extranodal ( n=2059), respectively. There was no significant difference in OS between the groups ( P=0.581) after IPTW adjustment. The most common primary sites in extranodal disease were skin, gastrointestinal tract, head and neck, and duodenum. The 10-year OS for skin, gastrointestinal tract, and cutaneous was 74.2%, 74.7%, and 87.3%, respectively, significantly higher than 55.6% for other sites (duodenum vs. others sites, gastrointestinal vs. others sites, skin vs. others sites: all P<0.001). Multivariate Cox regression analysis revealed that difference in OS was not significant among the intranodal groups or between the intranodal and extranodal groups. However, different extranodal primary site was an independent prognostic factor for OS. Conclusions:Early FL patients with supradiaphragmatic LN, subdiaphragmatic LN and Waldeyer's ring, and between the intranodal and extranodal primary sites obtain similar prognosis. However, early-stage FL patients with different extranodal primary sites have prognostic differences. The prognosis of primary skin, gastrointestinal tract and duodenum is significantly better than that of other extranodal primary sites.

Objective To design a training device of the flight crew for plateau normobaric low-oxygen acclimatization so as to enhance the flight crew's ability to adapt to the low oxygen environment after rushing into the plateau and reduce the incidence of acute plateau reaction.Methods The training device comprised a plateau environment simulation controller,a multimodal physiological acquisition system and hypoxia exercise training evaluation software.The plateau environment simulation controller was composed of an environment monitor for plateau acclimatization,two composite sensor sets,a control valve and an alarm device;the multimodal physiological acquisition system was made up of 20 groups of vital signs acquisi-tion devices,with a wearable dynamic ECG and respiration recorder,a wrist oximeter and an arm sphygmomano-meter included in each group.The hypoxia exercise training evaluation software was developed with a B/S architecture,Java language and JetBrains 2020.3.Results The training device proved to have the simulation altitude ranging from 0 to 6 000 m and facilitated simultaneous training of 20 persons for normobaric low-oxygen acclimatization,screening for hypoxia endurance,real-time monitoring of physiological parameters and assessment of training effect,with none of the trainees having acute plateau reaction.Conclusion The training device assists the flight crew for plateau normobaric low-oxygen acclimatization,and can be used for acclimatization training before plateau missions.[Chinese Medical Equipment Journal,2025,46(8):18-24]

Objective To evaluate the resuscitation efficacy of novel lyophilized platelets(LP,thrombin-stimulated platelets)combined with lactated Ringer's(LR)solution in rabbits with hemorrhagic shock and seawater immersion.Methods Fifty rabbits were randomly assigned to 5 groups(Groups A,B,C,D and E,n=10).After all rabbits were anesthetized with 3%pentobarbital sodium at a dose of 1 mL/kg,soft tissue injury was inflicted in the left lower limb.The blood loss from the soft tissue injury was quantified after gauze hemostasis.The right lower limb was subjected to femoral artery catheterization,followed by blood withdrawal equivalent to 26%of the total blood volume of the rabbit.The rabbits were then vertically immersed in 3%artificial seawater,with the water level reaching above the xiphoid process,and were retrieved in 15 min later.Resuscitation strategies were applied to the rabbits from different group:Group A(no resuscitation),Group B(resuscitation with LR solution),Group C(resuscitation with LR solution and fresh platelets),Group D(resuscitation with LR solution and LP),and Group E(resuscitation with LR solution and novel LP).Coagulation function test,routine blood test,blood gas analysis,and thromboelastography were conducted at baseline and at 1,2 and 4 h after injury.Results The LP and rabbit model of hemorrhagic shock and seawater immersion were successfully prepared.At 1 h after injury,the mean arterial pressure(MAP)of Groups C,D and E(infused with platelet preparations)was significantly higher than that of Group A(without resuscitation,P<0.05);the lactate(Lac)content of Group C was obviously lower than that of Groups A and B(P<0.05);the base excess(BE)and blood urea nitrogen(BUN)levels of Groups C,D and E were notably lower than those of Groups A and B(P<0.05);and the prothrombin time(PT)of Group A was significantly longer than that of before injury(P<0.05).At 2 h after injury,the MAP of Groups C and D was significantly higher than that of Groups A and B,and that of Group E was notably higher than that of Group A(P<0.05);the Lac content of Groups C and E was obviously lower than that of Groups A and B,while that of Group D was also lower than that of Group A(P<0.05);the BE and BUN levels of Groups C,D and E were remarkably lower than those of Groups A and B(P<0.05);the maximum amplitude(MA)value of Group C was higher than that of Group A,while the value of Groups A and D at this time was significantly lower than the corresponding value before injury(P<0.05);and the activated partial clotting time(APTT)of Groups A and D was statistically longer than the corresponding baseline time(P<0.05).At 4 h after injury,the MAP of Groups C,D,and E was higher than that of Groups A and B,and that of Group B was higher than that of Group A(P<0.05);the Lac and BUN levels of Groups C,D,and E were lower than those of Groups A and B(P<0.05);the BE level of Groups C and D were lower than those of Groups A and B(P<0.05);the MA value of Groups B,C,and E were higher than those of Group A(P<0.05),while the MA value and APTT value of Groups A and D were significantly lower than their corresponding baseline values(P<0.05).Conclusion For rabbits with hemorrhagic shock and seawater immersion,the novel LP combined with LR solution can significantly increase the MAP level,reduce Lac content,and sustainably maintain blood clot firmness and coagulation function.