OBJECTIVE To analyze the clinical characteristics and influential factors of drug-induced liver injury （DILI） in children caused by intravenous azithromycin. METHODS Clinical data of 157 DILI pediatric cases caused by intravenous azithromycin， reported by the Hengshui Adverse Drug Reaction Monitoring Center from January 2015 to January 2025， were collected as the observation group. Clinical data of pediatric patients who received intravenous azithromycin but did not develop DILI during the same period at Hengshui People’s Hospital were collected in a 1∶1 ratio to serve as the control group. The clinical classification， severity and prognosis of DILI in pediatric patients from the observation group were analyzed. Univariate and multivariate Logistic regression analyses were used to screen the independent risk factors for DILI in children caused by intravenous azithromycin. RESULTS Among 157 DILI cases， 92 cases （58.60%） had hepatocellular injury-type， 51 cases （32.48%） had cholestatic-type， and 14 cases （8.92%） had mixed-type. DILI severity was grade 1 in 117 cases （74.52%）， grade 2 in 33 cases （21.02%）， and grade 3 in 7 cases （4.46%）. Liver function had all recovered after stopping medication and symptomatic treatment. Combined with acetaminophen [OR＝3.769， 95%CI （1.615， 8.235）， P＝0.021]， daily dose of azithromycin＞10 mg/kg [OR＝ 2.237， 95%CI （1.075， 4.655）， P＝0.034] were independent risk factors for DILI in children caused by intravenous azithromycin. CONCLUSIONS Hepatocellular injury-type and cholestatic-type are relatively common in children with DILI caused by intravenous azithromycin， with mild severity being predominant and showing a favorable prognosis. Combination with acetaminophen and daily dose＞10 mg/kg are independent risk factors for azithromycin-induced DILI in children.

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Ovarian cancer poses a significant threat to women's health, necessitating effective therapeutic strategies. Emd-D, an emodin derivative, demonstrates enhanced pharmaceutical properties and bioavailability. In this study, Cell Counting Kit 8 (CCK8) assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D. Migration and invasion experiments confirmed its inhibitory effects on OVHM cells, while flow cytometry analysis demonstrated Emd-D-induced apoptosis. Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4. This was corroborated by alterations in intracellular lactate and pyruvate levels, as well as glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) expression. PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis. In vivo experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment, accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors. In conclusion, our findings demonstrate Emd-D's potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis. These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.
Female ; Humans ; Ovarian Neoplasms/physiopathology* ; Phosphofructokinase-2/genetics* ; Apoptosis/drug effects* ; Glycolysis/drug effects* ; Animals ; Cell Line, Tumor ; Mice ; Cell Proliferation/drug effects* ; Emodin/administration & dosage* ; Mice, Nude ; Mice, Inbred BALB C ; Hexokinase/metabolism* ; Xenograft Model Antitumor Assays

Objective To construct a Cox proportional hazards prediction model for secondary intracranial hypertension in patients with acute subdural hematoma (ASDH) during the perioperative period and validate its effectiveness. Methods Clinical data of 78 patients with ASDH were retrospectively collected and divided into secondary group (25 cases with secondary intracranial hypertension during perioperation) and control group (53 cases without secondary intracranial hypertension during perioperation). Differences in demographic indicators, comorbidities, clinical biochemical indicators, and imaging data between the two groups were compared. The Cox proportional hazards model was used to perform a multivariate analysis of independent risk factors that may affect secondary intracranial hypertension in ASDH patients during the perioperative period. A prediction model for secondary intracranial hypertension in ASDH patients during the perioperative period was established, and Harrell′s C index was calculated to assess the predictive accuracy of the model. The degree of agreement between the model prediction and actual risks was evaluated through a nomogram and calibration curve. Results The six-month follow-up rate was 89.74% (70/78). Age, smoking history, hypertension, diabetes, preoperative Glasgow Coma Scale (GCS) score, Glasgow Outcome Scale (GOS) score, complex hematoma, intracranial hematoma volume, mean arterial pressure, glycated hemoglobin (HbA1c), international normalized ratio (INR), interleukin-6 (IL-6), and procalcitonin (PCT) in the secondary group showed statistically significant differences compared with the control group (P < 0.05). Age(OR=2.895; 95%CI, 1.264 to 6.633; P=0.022), smoking history (OR=2.146; 95%CI, 1.029 to 4.475; P=0.036), GOS score (OR=0.288; 95%CI, 0.112 to 0.741; P=0.015), HbA1c (OR=3.325; 95%CI, 1.243 to 8.894; P=0.028), INR (OR=2.746; 95%CI, 1.203 to 6.267; P=0.027), and PCT (OR=3.426; 95%CI, 1.335 to 8.795; P=0.019) were independent influencing factors for secondary intracranial hypertension in ASDH patients during the perioperative period. Harrell′s C index was 0.812 (95%CI, 0.789 to 0.872). The nomogram and calibration curve showed good consistency between the actual risk and the model prediction. Conclusion Cox proportional hazards model for patients with acute subdural hematoma has high accuracy in predicting the risk of secondary intracranial hypertension during the perioperative period and is suitable for clinical promotion.

Endothelial-mesenchymal transition (EndMT) disrupts vascular endothelial integrity and induces atherosclerosis. Active integrin β1 plays a pivotal role in promoting EndMT by facilitating TGFβ/Smad signaling in endothelial cells. Here, we report a novel anthraquinone compound, Kanglexin (KLX), which prevented EndMT and atherosclerosis by activating MAP4K4 and suppressing integrin β1/TGFβ signaling. First, KLX effectively counteracted the EndMT phenotype and mitigated the dysregulation of endothelial and mesenchymal markers induced by TGFβ1. Second, KLX suppressed TGFβ/Smad signaling by inactivating integrin β1 and inhibiting the polymerization of TGFβR1/2. The underlying mechanism involved the activation of FGFR1 by KLX, resulting in the phosphorylation of MAP4K4 and Moesin, which led to integrin β1 inactivation by displacing Talin from its β-tail. Oral administration of KLX effectively stimulated endothelial FGFR1 and inhibited integrin β1, thereby preventing vascular EndMT and attenuating plaque formation and progression in the aorta of atherosclerotic Apoe^-/- mice. Notably, KLX (20 mg/kg) exhibited superior efficacy compared with atorvastatin, a clinically approved lipid-regulating drug. In conclusion, KLX exhibited potential in ameliorating EndMT and retarding the formation and progression of atherosclerosis through direct activation of FGFR1. Therefore, KLX is a promising candidate for the treatment of atherosclerosis to mitigate vascular endothelial injury.
Animals ; Atherosclerosis/prevention & control* ; Mice ; Receptor, Fibroblast Growth Factor, Type 1/metabolism* ; Signal Transduction/drug effects* ; Anthraquinones/pharmacology* ; Humans ; Integrin beta1/metabolism* ; Epithelial-Mesenchymal Transition/drug effects* ; Male ; Transforming Growth Factor beta/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Human Umbilical Vein Endothelial Cells/drug effects*

Objective To quantify the setup errors for the different anatomical sites of patients who received intensity-modulated radiotherapy (IMRT) with linear accelerator on-board kilovolt fan beam CT(kV-FBCT) as non-isocenter IGRT and megavolt cone beam CT (MV-CBCT) as isocenter IGRT. Methods A retrospective analysis was performedon 70 patients who underwent radiotherapy, kV-FBCT, and/or MV-CBCT scans after each routine setup prior to IMRT. The average displacement (M), systematic error (Σ), and random error (б) at different treatment sites in the left-right, anterior-posterior, and cranial-caudal directions were calculated according to the individual displacements. The formula 2.5Σ+0.7б was used to estimate the PTV margin in respective direction. For each single patient, the root mean square in three directions was used as 3D displacement. Results A total of 1130 displacements were recorded in the 70 patients. The PTV margin was estimated to be 1.9-3.1 mm in head and neck cancer, 2.8-5.1 mm in thoracic cancer, 4.6-5.1 mm in breast cancer, 3.0-5.5 mm in upper abdominal cancer, and 3.5-6.8 mm in pelvic tumor. For the 3D mean displacements, the head and neck, thoracic, breast, upper abdominal, and pelvic cancer were 2.4±1.0, 4.0±1.6, 4.1±2.0, 4.6±2.1, and 4.6±2.1 mm, respectively. The average 3D displacement obtained by kV-FBCT and MV-CBCT were 4.1 and 3.4 mm, respectively (P=0.212). Conclusion The quantitative setup-error data can be obtained using linear accelerator on-board FBCT, and the non-isocenter IGRT induced set-up error cannot be negligible.

Objective To study epidemic of schistosomiasis in the Qiandao Lake reservoir area,and to provide a reference for prevention and control of schistosomiasis in the construction of large water conservancy projects in the epidemic area of schistosomiasis.Methods The data over the years of snail condition and monitoring of schistosomiasis before and after building the dam,and water conservancy project reconstruction related information were collected.Based on the survey results of the river channel,the lake beach and the dissipation zone in the reservoir area,the influence of Xin'an River water conservancy project on epidemic of schistosomiasis in the Qiandao Lake reservoir area was analyzed,and the epidemic factors of the schistosomiasis in the Three Gorges reservoir were compared and analyzed.Results Before the dam was built,an area of 38 144 000 m2 was examined but Oncomelania was undetected.The Qiandao Lake reservoir area belonged to a non epidemic area of schistosomiasis.After the dam was built,557 cases of schistosomiasis were found in 6 232 immigrants during 1962-1965,resulting in an imported epidemic.In 1970-1980,an area of 379 654 m2 in which Oncomelania was found was examined and snails were mainly distributed in some rice fields and ditches in the end of the reservoir.949 cases of local schistosomiasis were found in the snails.The condition and condition of the snail are gradually controlled through several decades of comprehensive prevention and control.Compared with the epidemic factors of schistosomiasis in Qiandao Lake and the Three Gorges reservoir,the environment of elevation beach and ecologically fragile fluctuation zone coexist in the two reservoir areas.Conclusion From the long-term longitudinal monitoring data of the Qiandao Lake reservoir area and the epidemic regularity of schistosomiasis and the comparison with the ecology of the Three Gorges reservoir,it is concluded that the two reservoir areas will not cause a large range of schistosomiasis epidemic in general,but it does not exclude the possibility of the breeding of the inputting Oncomelania.

Objective To investigate the effect of carotid sympathetic nerve net stripping operation in treating children patients with spastic unilateral cerebral palsy and its effect on motor function.Methods Seventy-six children cases of spastic unilateral cerebral palsy were divided into the control group and observation group.On the basis of routine therapy,the former was treated with type A botulinum toxin,while the latter used the carotid sympathetic nerve netting operation for the treatment.After 6-month treatment,the improvement degree of the Comprehensive Functional Rating Scale of Cerebral Palsy Children,Gross Motor Function Measure(GMFM) score and Ashworth spasm grade were compared between the two groups.Results after 6-month treatment,the improvement degrees of the Comprehensive Functional Rating Scale of Cerebral Palsy Children,GMFM scores and Ashworth spasm grade in the observation group were significantly greater than those in the control group,the difference was statistically significant (P＜0.05).Conclusion The carotid sympathetic nerve net stripping operation in treating children patients with spastic unilateral cerebral palsy has significant effect and is worthy to be popularized in clinic.

Objective To investigate the clinical efficacy of L1 -S1 selective posterior rhizotomy (SPR)at the medullary conus level for the treatment of double lower extremities spastic cerebral palsy(CP).Methods A total of 1 09 double lower extremities spastic CP children underwent SPR at the level of medullary consul were selected in the Second Affiliated Hospital of Xinjiang Medical University from October 201 0 to May 201 4.The 4 groups were analyzed in terms of muscle tension and gross motor function of the lower limbs 6 months before and after operation,retrospective-ly.The SPSS 1 7.0 software was used for statistical analysis.Results Patients had different degrees of improvement in gross motor function and reduction of spasticity in all muscle groups of lower limbs after operation.Six months after the operation,the muscular tension of hip flexor,hip adductor,knee flexor and plantar flexors (modified Ashworth spastic scale score)were all improved compared with preoperation (t =1 6.635,27.41 1 ,31 .362,38.81 9,all P <0.01 ).Gross motor function of lower limbs (Gross Motor Function Measure)at 6 months after the operation was significantly im-proved compared with preoperation (51 .97 ±1 2.92 vs 41 .01 ±1 1 .46),and the difference was significant(t =26.67, P <0.01 ).The postoperative complications:intracranial hypotension headache (5 cases,4.59%),postoperative high fever (2 cases,1 .83%),incision fat liquefaction (2 cases,1 .83%),sensory barriers of lower limbs (1 case, 0.92%),and urine obstacles (1 case,0.92%).Conclusions SPR at the level of medullary conus has the advantages of minimal injury,rapid recovery and little influence on the stability of the spine.In addition,the procedure can relieve the spasticity of lower limbs of the CP patients effectively.

The morbidity of diabetes has been increasing rapidly in recent years. Delayed wound healing has become a common complication in diabetes, which seriously affects the orthobiosis of patients. Exploring and finding the molecular mechanisms of diabetic wound healing and the effective therapies to promote wound healing have important clinical significances. Stem cells transplant has become a research hotspot in accelerating diabetic wound healing. This article reviewed the present approaches concerning stem cells transplant in diabetic wound healing both at domestic and abroad, and looked forward the clinical therapy of stem cells on diabetic wound healing.