Objective To systematically evaluate toxicities of nifedipine in pregnant women with hypertension, and provide references for nifedipine’s clinical safety application. Methods Study was conducted with data from US food and drug administration adverse event reporting system（FARES） database from January 1, 2015, to March 31, 2021. Information component （IC） and reporting odds ratio（ROR）methods were applied for signal mining. Results Finally, a total of 539278 records of pregnant women with hypertension were selected for analysis, and 70 positive adverse drug event signals were detected. Premature delivery （IC₀₂₅=2.87，ROR₀₂₅=9.52）, pre-eclampsia （IC₀₂₅=1.82，ROR₀₂₅=3.82） and fetal growth restriction （IC₀₂₅=2.37，ROR₀₂₅=5.69）were positive adverse events with higher frequency. Polydactyly（IC₀₂₅=3.13， ROR₀₂₅=10.05）, fetal death（IC₀₂₅=2.93，ROR₀₂₅=8.57）and premature delivery（IC₀₂₅=2.87，ROR₀₂₅=9.52）were positive adverse events with higher intensity. Vascular resistance systemic increased, small for dates baby and fetal death corresponded to higher death rates. Conclusion Nifedipine-associated drug toxicities were detected in pregnant women with hypertension, and some adverse events with high frequency and high death rate were deserved further attention by medical staffs.

BACKGROUND: Pre-transplant exposure to immune checkpoint inhibitors (ICIs) significantly increases the risk of allograft rejection after liver transplantation (LT); however, whether ICI-related rejection leads to increased graft loss remains controversial. Therefore, this study aimed to investigate the association between ICI-related allograft rejection and perioperative graft loss. METHODS: This was a retrospective analysis of adult liver transplant recipients with early biopsy-proven T-cell-mediated rejection (TCMR) at Liver Transplantation Center of Sun Yat-sen Memorial Hospital from June 2019 to September 2024. The pathological features, clinical characteristics, and perioperative graft survival were analyzed. RESULTS: Twenty-eight patients who underwent early TCMR between June 2019 and September 2024 were included. Based on pre-LT ICI exposure, recipients were categorized into ICI-related TCMR (irTCMR, n = 12) and conventional TCMR (cTCMR, n = 16) groups. Recipients with irTCMR had a higher median Banff rejection activity index (RAI) (6 vs . 5, P = 0.012) and more aggressive tissue damage and inflammation. Recipients with irTCMR showed higher proportion of treatment resistance, achieving a complete resolution rate of only 8/12 compared to 16/16 for cTCMR. Graft loss occurred in 5/12 of irTCMR recipients within 90 days after LT, with no graft loss in cTCMRs recipients. Cox analysis demonstrated that irTCMR with an ICI washout period of <30 days was an independent risk factor for perioperative graft loss (hazard ratio [HR], 6.540; 95% confidence interval [CI], 1.067-40.067, P = 0.042). CONCLUSION IrTCMR is associated with severe pathological features, increased resistance to treatment, and higher graft loss in adult liver transplant recipients.
Humans ; Liver Transplantation/adverse effects* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Graft Rejection/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; T-Lymphocytes/drug effects* ; Graft Survival/immunology* ; Aged

Objective:To summarize the clinical characteristics of patients with epilepsy caused by focal cortical dysplasia (FCD), and identify the influencing factors for postoperative seizure controls.Methods:Fifty-seven patients with epilepsy caused by FCD admitted to Department of Neurosurgery, Third Affiliated Hospital of Zhengzhou University from July 2019 to November 2023 were chosen; standard preoperative evaluation, surgery, postoperative management and follow-up were performed. A retrospective study of clinical data, imaging and video electroencephalogram (VEEG) data, surgical approaches, pathological findings, and follow-up data was performed; influencing factors for postoperative seizure controls were analyzed.Results:In these 57 patients with epilepsy caused by FCD, 29 were males (50.88%) and 28 were females (49.12%). Onset age was 30.00 (8.00, 74.50) months, and surgery age was 95.00 (50.00, 138.50) months. Focal to bilateral tonic-clonic seizures (42/57; 73.68%) and epileptic spasms (13/57; 22.81%) were common seizure types. Cranial MRI was positive in 34 patients (59.65%), mainly manifested as abnormal cortical gyri/sulci morphology (17/57; 29.82%). In 43 patients accepted PET-CT, hypometabolic sites were detected in 40 (93.02%), and complete agreement between PET/MRI fusion results and actual lesion sites was noted in 40 (93.02%). FCD type I was noted in 16 patients (28.07%), type II in 39 (68.42%), and type III in 2 (3.51%). By December 2023, 44 (77.19%) had Engel grading I, 4 (7.02%) had grading II, 4 (7.02%) had grading III, and 5 (8.77%) had grading IV. Children with good prognosis (Engel grading I+II) and those with poor prognosis (Engel grading III+IV) showed significant differences in terms of time from first seizure to surgery, positive/negative MRI, and regularity of postoperative ASMs ( P<0.05). Conclusions:Focal to bilateral tonic-clonic seizure is the most common seizure type in patients with epilepsy caused by FCD, and abnormal cortical gyri/sulci morphology is the most common MRI manifestation; PET/MRI fusion imaging is superior to PET-CT or MRI in identifying epileptogenic foci. Poor seizure control can be noted in patients with long onset time to surgery, with negative cranial MRI results, or with irregular postoperative ASMs.

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat.This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression.Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

Blood-retina barrier destruction, nerve injury, formation of neovascularization and fibroblast proliferation membrane are important pathological changes of DR, which are related to the combined effects of various vitreous cytokines. VEGF is mainly involved in increasing retinal vascular permeability and inducing neovascularization. Pigment epithelium derived factor is vital reducing vascular permeability and neuroprotection; IL plays a key role in mediating inflammatory response. TNF-α is related to inflammation, which is significantly up-regulated by hypoxia. TGF-β is an important cytokine regulating cell proliferation and differentiation. Connective tissue growth factor can promote the growth, migration and adhesion of endothelial cell. In addition, many other molecular mechanisms have not been fully elucidated, and further study on the molecular mechanism of DR is urgent. With the further study of molecular mechanism, the early intervention and targeted treatment of DR will be more effective.

Objectives To research clinical effects of severe brain injury patients treated by acupuncture and herb combine mild hypothermia,discuss the new approach of severe brain injury patients treatment combine Chinese traditional and Western medicine.Methods Investigated 68 severe traumatic brain injured patients,randomly divided into three groups,acupuncture and herb combine mild hypothermia group (n =22),mild hypothermia group (n =24) and normal temperature routine treatment group (n =22).Dynamic intracranial pressure,brain damage index (cytoskeletal protein),immunologic function (IL-6,β2 microglobulin),combine rate of complications (including irritable ulcer,lung infection,epilepsy,sugar metabolism disorder,and so on),and long-term GOS score were analyzed.SPSS12.0 software was used for statistical processing,and the standard deviation of the measurement data were expressed as the standard deviation.The counting data were expressed as apercentage,and the chi-square test was used for the comparison between group.Results There were significant differences between three groups of intracranial pressure,immunologic function,complication occurring rate (P ＜0.05),but there had no significant difference between acupuncture and herb combine mild hypothermia group and mild hypothermia group of brain damage index and GOS,and there have significant difference between these two groups and normal temperature routine treatment group.Conclusions Acupuncture and herb combined mild hypothermia might be better in reducing intracranial pressure,the incidence of complication,and improving immune function of severe brain injury,than mild hypothermia group and normal temperature routine treatment group.

OBJECTIVE:To provide reference for rational use of Shexiang tongxin dripping pills in clinic. METHODS:In retrospective study,the utilization of Shexiang tongxin dripping pills in outpatients and inpatients of our hospital during Jan. 2014-May 2015 was analyzed statistically in terms of gender,age,department,irrational drug use,ADR and DUI,etc. RE-SULTS:There were 719 outpatient prescriptions and 281 inpatient medical orders. The female was more than male with ratio of 1.42:1. Most patients aged 80-89 year-old(35.4%). Shexiang tongxin dripping pills were mostly used in cardiovascular medicine de-partment(760 pieces/copies,76.0%). There were 72 prescriptions/medical orders that did not conform to the indications(7.2%), and 7 prescriptions/medical orders for overdose use(0.7%). No obvious ADR was found. DUI of Shexiang tongxin dripping pills was 1.007. CONCLUSIONS:Although the clinical use of Shexiang tongxin dripping pills in our hospital is basically rational,there still are some nonstandard uses,which should be taken seriously. In order to reduce ADR,the clinical use of Shexiang tongxin dripping pills should be strictly in accordance with the drug instructions and should emphasize the syndrome differentiation based on treatment.

Objective To explore the diagnostic evidence and treatment strategies for steroid-resistant acute rejection (SRAR) after orthotopic liver transplantation.Methods A retrospective analysis was performed among 1038 patients undergoing orthotopic liver transplantation in our hospital from January 2004 to December 2013.A total of 169 acute rejection (AR) episodes occurred in 153 patients.Sixteen of the patients were diagnosed with SRAR because of no response to large-dose steroid pulse therapy.The diagnosis and treatment of the 16 patients were analyzed retrospectively.Comparison of data was made by x2 test or t test,and a P value of＜0.05 was considered to be significant.Results The incidence of AR after liver transplantation was 14.74％ (153/1038) in all the patients.The incidence of SRAR was 9.47％ (16/169) in patients with AR.In the 16 patients with SRAR,3 were treated with anti-CD3 monoclonal antibody (OKT3),9 were treated with monoclonal antibody against IL-2 receptor,and 4 received antithymocyte globulin (ATG) therapy.After treatment,SRAR was reversed in 12 of the 16 patients and caused death of the other 4 patients,yielding a reversal rate of 75％ and a mortality rate of 25％.Conclusion SRAR after liver transplantation has a low incidence rate but poor prognosis.The diagnosis of SRAR is mainly based on the clinical manifestation,laboratory test,liver biopsy,and poor response or rejection to methyl prednisolone pulse therapy.ATG and OKT3 achieve substantial outcomes in most of the patients in the treatment of SRAR.Particularly,compared with OKT3,ATG achieves a higher reversal rate and fewer adverse reactions,which is expected to become the first-line treatment of SRAR.

To construct a library of mouse single chain variable fragment (scFv) antibody against ofloxacin using phage display and recombinant antibody technique, specific anti-ofloxacin scFv was screened and 3D structure was homology modeling. Total RNA was extracted from hybridoma cell of ofloxacin mAb, and was used to amplify VH and VL gene by RT-PCR using random primer. Then they were linked by a DNA linker encoding (G1y4 Ser) 3 as VH-linker-VL sequence forming scFv by SOE(splicing by overlap extension) PCR. These fragments were inserted into phage T7 after double digestion and transformed with host bacteria BLT5403. 3 ×105 pfu / ml single chain antibody phage libraries were successfully constructed. Four positive phage scFv clones were screened by direct competitive ELISA after four times of enriched procedure in the order of adsorption-elution-amplificatio, 3D structure of specific scFv was homology modeling finally. This research lays a foundation for further massive expression of anti-ofloxacin scFv.