Objective To analyze the clinical characteristics of immune checkpoint inhibitor (ICI)-related hypophysitis. Methods A retrospective analysis was conducted on patients diagnosed with ICI-related hypophysitis and treated at the Department of Endocrinology, The First Affiliated Hospital with Nanjing Medical University, between January 2020 and March 2025. Clinical manifestations and prognosis of patients were analyzed. Results Eleven patients with ICI-related hypophysitis were included. The average age was (62.27±7.63) years, and 9 patients (81.82%) were male. The median time to onset was 9.1 months, and the median number of treatment cycles received was 5. The primary initial symptoms were fatigue and anorexia. Hyponatremia was present in 3 patients (27.27%). Evaluation of anterior pituitary function revealed adrenocorticotropic hormone deficiency as the most common manifestation (90.91%, 10/11), followed by hyperprolactinemia (81.82%, 9/11). Posterior pituitary function remained normal in all patients. Pituitary magnetic resonance imaging showed no abnormality in 4 patients (44.44%). Thyroid dysfunction was observed in 6 patients (54.55%), one of whom (9.09%) also exhibited pancreatic endocrine dysfunction. The average follow-up duration was 36.5 months. Eight patients (72.73%) were alive at the last follow-up. None of the patients recovered their pituitary hormone function. Conclusions Endocrine adverse events induced by ICIs can involve multiple glandular systems. Clinicians should be highly vigilant for the possibility of ICI-induced hypophysitis in patients receiving ICIs who present with symptoms such as fatigue, anorexia, and hyponatremia.

OBJECTIVES: To investigate the clinicopathological characteristics and prognostic factors of pediatric Hodgkin lymphoma (HL). METHODS: A retrospective analysis was conducted on the clinical data of children with newly diagnosed HL from January 2011 to December 2023 at four hospitals: Fujian Medical University Union Hospital, Fujian Medical University Zhangzhou Hospital, First Affiliated Hospital of Xiamen University, and Fujian Children's Hospital. Patients were categorized into low-risk (R1), intermediate-risk (R2), and high-risk (R3) groups based on HL staging and pre-treatment risk factors. The patients received ABVD regimen or Chinese Pediatric HL-2013 regimen chemotherapy. Early treatment response and long-term efficacy were assessed, and prognostic factors were analyzed using the Cox proportional hazards regression model. RESULTS: The overall complete response (CR) rates after 2 and 4 cycles of chemotherapy were 42% and 68%, respectively. Compared with the ABVD regimen group, patients treated with the HL-2013 regimen in the R1 group showed significantly higher CR rates after both 2 and 4 cycles (P<0.05). However, no statistically significant differences in CR rates were observed between the two regimens in the R2 and R3 groups (P>0.05). The 5-year event-free survival (EFS) rate, overall survival rate, and freedom from treatment failure rate were 83%±4%, 97%±2%, and 88%±4%, respectively. Cox analysis indicated that the presence of a large tumor mass at diagnosis and failure to achieve CR after 4 cycles of chemotherapy were independent risk factors for lower EFS rates (P<0.05). CONCLUSIONS Pediatric HL generally has a favorable prognosis. The presence of a large tumor mass at diagnosis and failure to achieve CR after 4 cycles of chemotherapy indicate poor prognosis.
Humans ; Hodgkin Disease/pathology* ; Male ; Child ; Female ; Adolescent ; Retrospective Studies ; Child, Preschool ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Prognosis ; Proportional Hazards Models ; Survival Analysis ; Infant

OBJECTIVE: To investigate the protective effect of achyranthes bidentata (AB) on sperm quality in mice with spermatogenic disorder through the glycolytic metabolic pathway and its action mechanism. METHODS: We equally randomized 40 Kunming mice into a normal control, a model control, a low-dose AB (3.5 g/kg) and a high-dose AB group (7.0 g/kg), and established the model of spermatogenic disorder in the latter three groups of mice by intraperitoneal injection of doxorubicin (30 mg/kg). Two days after modeling, we collected the testis and kidney tissues and blood samples from the mice for observation of the pathological changes in the testis tissue by HE staining, detection of perm motility with the sperm quality analyzer, examination of the apoptosis of testis cells by flow cytometry, measurement of the levels of testosterone (T), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in the serum and testis tissue by ELISA, and determination of expressions of the key enzymes of glycolysis hexokinase Ⅱ (HK2), pyruvate kinase M2 (PKM2), platelet phosphofructokinase (PFKP), lactate dehydrogenase A (LDHA) and the meiosis proteins REC8 and SCP3 by Western blot, and the mRNA expressions of glycolytic phosphofructokinase 1 (PFK1), phosphoglycerate kinase 1 (PGK1), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) by fluorescence quantitative PCR (FQ-PCR). RESULTS: Compared with the model controls, the mice in the AB groups showed significant increases in the testis coefficient, kidney index, sperm concentration, sperm motility, spermatogonia, primary spermatocytes, spermatids, sperm count and the serum T level (P<0.05 or P<0.01), but dramatic decreases in the apoptosis of testis cells and percentage of morphologically abnormal sperm (P<0.01). Achyranthes bidentata also significantly elevated the levels of SOD and CAT, and down-regulated the mRNA expressions of MDA, TNF-α and IL-1β (P<0.05 or P<0.01), and up-regulated the protein expressions of HK2, PKM2, PFKP, LDHA, REC8 and SCP3, and expressions of the glycolysis key genes Pfk1 and Pgk1 (P<0.05 or P<0.01). CONCLUSION Achyranthes bidentata ameliorates doxorubicin-induced spermatogenic disorder in mice by regulating the glycolytic pathway and reducing oxidative stress and the expressions of inflammatory factors.
Glycolysis/drug effects* ; Doxorubicin/toxicity* ; Spermatogenesis/drug effects* ; Random Allocation ; Male ; Animals ; Mice ; Disease Models, Animal ; Achyranthes/chemistry* ; Spermatozoa/pathology* ; Oxidative Stress/drug effects* ; Primary Cell Culture ; Apoptosis/drug effects* ; Sperm Motility/drug effects* ; Testis/pathology* ; Infertility, Male/prevention & control* ; Medicine, Chinese Traditional/methods* ; Animals, Outbred Strains

Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL_(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL_(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Important forensic diagnostic indicators of sudden death in coronary atherosclerotic heart dis-ease,such as acute or chronic myocardial ischemic changes,sometimes make it difficult to locate the ischemic site due to the short death process,the lack of tissue reaction time.In some cases,the de-ceased died of sudden death on the first-episode,resulting in difficulty for medical examiners to make an accurate diagnosis.However,clinical studies on coronary instability plaque revealed the key role of coronary spasm and thrombosis caused by their lesions in sudden coronary death process.This paper mainly summarizes the pathological characteristics of unstable coronary plaque based on clinical medi-cal research,including plaque rupture,plaque erosion and calcified nodules,as well as the influencing factors leading to plaque instability,and briefly describes the research progress and technique of the atherosclerotic plaques,in order to improve the study on the mechanism of sudden coronary death and improve the accuracy of the forensic diagnosis of sudden coronary death by diagnosing different patho-logic states of coronary atherosclerotic plaques.

Objective To observe the effect of catgut implantation at acupoint(CIAA)on the learning and memory function,hippocampal microangiogenesis,and the mRNA and protein expression of angiopoietin-1(Ang-1)/vascular endothelialgrowth factor(VEGF)and its receptor TEK tyrosine kinase(TIE2)/VEGF receptor 2(VEGFR2)in rats with vascular dementia(VD).To explore the mechanism of catgut implantation at acupoint in preventing and treating VD.Methods Using a random number table,VD rats were divided into a model group,a nimodipine group,and an catgut implantation at acupoint group,and a sham operation group was set up,with 10 rats in each group.On the 7th day after surgery,the treatment groups were given catgut implantation at acupoint and nimodipine gastric lavage for 21 days.After treatment,Morris water maze behavioral test was performed.HE staining was used to observe hippocampal CA1 tissue.CD34 immunohistochemical staining was used to detect hippocampal microvascular density(MVD).Real-time PCR and Western blotting were used to detect the mRNA and protein expression of Ang-1/VEGF and its receptor TIE2/VEGFR2 in the hippocampus.Results Compared with the model group,the average escape latency of the other groups was significantly shortened,and the target quadrant residence time was significantly prolonged(P<0.01,P<0.05).Compared with the model group,the number of nucleolus and well-formed pyramidal cells in hippocampal CA1 area of the catgut implantation at acupoint group and the nimodipine group increased in varying degrees,and they were arranged more closely,with only a few cells scattered and swollen.In the sham surgery group,a few CD34 positive cells were scattered.The treatment groups had more closely distributed CD34 positive cells with significant staining compared to the model group.The MVD of the model group was significantly higher than that of the sham surgery group(P<0.01).Both nimodipine group and catgut implantation at acupoint group had higher MVD than the model group(P<0.05,P<0.01).Compared with the sham surgery group,the mRNA and protein expression of Ang-1/VEGF and its receptor TIE2/VEGFR2 in the model group increased significantly(P<0.01,P<0.05).Compared with the model group,both nimodipine group and catgut implantation at acupoint group had higher mRNA and protein expression of Ang-1/VEGF and its receptor TIE2/VEGFR2(P<0.01,P<0.05).Conclusion Catgut implantation at acupoint can improve the learning and memory abilities in VD rats,promote hippocampal microvascular angiogenesis,which may be related to the up-regulation of Ang-1/VEGF and its receptor TIE2/VEGFR2 mRNA and protein expression.

Hemorrhagic shock (HS) is one of the leading causes of death among young adults worldwide. Multiple organ dysfunction in HS is caused by an imbalance between tissue oxygen supply and demand, which is closely related to the poor prognosis of patient. Mitochondrial dysfunction is one of the key mechanisms contributing to multiple organ dysfunction in HS, while mitochondrial quality control regulates mitochondrial function through a series of processes, including mitochondrial biogenesis, mitochondrial dynamics, mitophagy, mitochondrial-derived vesicles, and mitochondrial protein homeostasis. Modulating mitochondrial quality control can improve organ dysfunction. This review aims to summarize the effects of mitochondrial dysfunction on organ function in HS and discuss the potential mechanisms of mitochondrial quality control, providing insights into the injury mechanisms underlying HS and guiding clinical management.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.