Objective To observe the effect of exogenous basic fibrob last growth factor (bFGF) on apoptosis of cultured human retinal pigment epithelial (RPE) cells exposed to visible light,and determine the role of bFGF, fibroblast growth factor receptor 1 (FGFR1),bcl-2 and caspase-3. Methods 2000±500) lx cold white light was used. Exogenous bFGF was utilized during culture. Annexin annexin V-fluoresce in isothiocyanate/propidium iodium (V-FITC/PI) labeling,flow cytometry, Immunocytochemical staining, enzyme associated absorb examing and reverse transcriptional polymerase chain reaction (RT-PCR) were used to determine the apoptosis, the expression levels of bFGF, FGFR1, bcl-2, as well as the activity of caspase-3. Results No protective effect of bFGF was observed under the concentration 5 ng/ml.A significant inhibition of apoptosis was found in 10 ng/ml and 20 ng/ml groups （P＜0.05）. The upregulation of bcl-2 was observed in bFGF (10 ng/ml, 20 ng/ml) protreated groups（P＜0.01）.Compared to no light exposure group,all light exposure groups (including bFGF pro-treated) had higher endogenous bFGF and FGFR1 levels （P ＜0.05）, and the increase was concentration dependent.The bFGF and FGFR1 levels were higher in exogenous bFGF applied (gt;5 ng/ml) groups than light exposure groups（P＜0.05）. The caspase-3 activity was significantly inhibited in bFGF (10 ng/ml) pro-treated groups. Conclusions Human RPE cells exposed to visible light were rescued by application of exogenous bFGF in vitro.The probable protective mechanism of bFGF partly is directly binding to FGFR1 or potentiating endogenous bFGF autocrine loop,to upregulate bcl-2 and to inhibit caspase-3 activation. (Chin J Ocul Fundus Dis，2003，19：24-28)
Objective To investigate the damage to the retinal cells and apoptosis of retinal cells of rats after ischemia-reperfusion insult. Methods The retinal ischemia-reperfusion model was developed by increasing intraocular pressure to 109725 mm Hg in rat eyes. Morphological changes of the rat eyes were observed by means of routine histopathology with HE staining. Apoptosis of the retina was assayed by both DNA fragmentation gel-electrophoresis and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL). Results Compared with the normal control, no histopathological changes were revealed in the rat retinas 30 min after the ischemia and then reperfued for 24 h or 48 h. Retinal ganglion cell layer (RGL) and inner plaxiform layer (IPL) of the retina were observed, however, to become significantly thinner 60 min after the ischemia and then reperfued for 24 h or 48 h. Together with the pathological changes DNA ladder pattern was detected in the same group of the rats. Further, immunochemical stain of the eye demonstrated that TUNEL positive cells were localized in RGL and IPL of the retina. Conclusion Ischemia-reperfusion insult of the eye may remarkably damage the retina of the rat eye. The damage to the retinal cells is mainly localized within RGL and IPL and apoptosis is the important mechanism of the retinal disorder. (Chin J Ocul Fundus Dis, 2002, 18: 296-298)
Objective To investigate the effects of epidermal growth factor (EGF)，fibroblast growth factor(FGF), and bovine serum on proliferation and apoptosis of the cultured fetal human retinal cells.Methods EGF and FGF were added or not to the medium of fetal human retinal cells cultured by bovine serum in vitro. The number of cells, bromodeoxyuridine(BrdU) incorporation and Tdt-mediated dUTP nick end labelling(TUNEL) were detected to determine the proliferation and apoptosis. Immunohistochemical staining of neuron specific enolase(NSE), Thy1.1, glial fibrillary acidic protein(GFAP) and scan electromicroscopy were performed to identify cell components. The expression of transcription factor c-fos, c-jun and apoptosis regulation factor bcl-2 and Bax were examined by immunohistochemical staining to explore the underlying mechanism.Results The increased number of NSE and Thy1.1 positive cells and BrdU incorporation, and decreased apoptotic cells were found in the groups treated with EGF and FGF. Meanwhile, the up-regulation of c-fos, c-jun and bcl-2 were also found. Conclusion EGF and FGF can promote the survival and proliferation of cultured retinal cells by up-regulating the expression of c-fos, c-jun and bcl-2. (Chin J Ocul Fundus Dis，2003，19：113-116)
Objective To analyze the clinical features of immune checkpoint inhibitor-related pneumonia (CIP) in patients with lung cancer. Methods The case data of patients with CIP admitted to Zhongshan Hospital of Fudan University from January 2017 to December 2020 were retrospectively collected, and the basic data, clinical manifestations, imaging data, laboratory examination results, treatment and prognosis of the patients were analyzed. Results The ratio of male to female was 18:1, and the median age was 65 years (from 41 to 74 years). Fourteen patients received a programmed death protein-1 (PD-1) inhibitor and five patients received a programmed death protein-ligand-1 (PD-L1) inhibitor. The median time to CIP was 3.5 months. The respiratory symptoms of 15 patients were dyspnea in 11 cases, cough in 9 cases, chest tightness in 8 cases, fever in 4 cases, expectoration in 4 cases and hemoptysis in 2 cases. Chest CT findings mainly showed interstitial pneumonia, including 8 cases of implicit organizational pneumonia (COP), 7 cases of non-specific interstitial pneumonia (NSIP), 2 cases of acute interstitial pneumonia, and 2 cases of allergic pneumonia. C-reactive protein, erythrocyte sedimentation rate and lactate dehydrogenase were higher in CIP than before, and the difference was statistically significant. Follow-up observation was performed in 3 patients alone, 14 patients were treated with glucocorticoid alone, 2 patients were treated with immunosuppressant therapy, 19 patients had stable or more absorption of pneumonia lesions, and 5 patients had restarted immunotherapy. There were no deaths from CIP. Conclusions CIP mainly occurs in men, with slow onset, lack of specificity in clinical manifestations, and increased inflammatory indicators. Imaging findings are mainly NSIP and COP changes. Early identification, diagnosis and rational application of glucocorticoid therapy have good effects.
Objective To summarize the research progress of programmed cell death protein 1 (PD-1)/programmed cell death protein-ligand 1 (PD-L1) inhibitors before liver transplantation of liver cancer. Method The literatures on the application of PD-1/PD-L1 inhibitors before liver transplantation of liver cancer were collected and reviewed. Results PD-1/PD-L1 inhibitors preoperatively treated liver transplantation recipients had a low incidence of postoperative rejection, and routine usage of hormone and immune tolerance induction therapy in liver transplantation recipients might reduce the incidence of rejection caused by PD-1/PD-L1 inhibitors. Conclusion Preoperative usage of PD-1/PD-L1 inhibitors have more benefits than risks for patients with advanced liver cancer.
ObjectiveSeizure-related respiratory or cardiac dysfunction was once thought to be the direct cause of sudden unexpected death in epilepsy (SUDEP), but both may be secondary to postictal cerebral inhibition. An important issue that has not been explored to date is the neural network basis of cerebral inhibition. Our aim was to investigate the features of neural networks in patients at high risk for SUDEP using a blood oxygen level-dependent (BOLD) resting-state functional MRI (Rs-fMRI) technique. MethodsRs-fMRI data were recorded from 13 patients at high risk for SUDEP and 12 patients at low risk for SUDEP. The amplitude of low-frequency fluctuations (ALFF) values were compared between the two groups to decipt the regional brain activities. ResultsCompared with patients at low risk for SUDEP, patients at high risk exhibited significant ALFF reductions in the right superior frontal gyrus, the left superior orbital frontal gyrus, the left insula and the left thalamus; and ALFF increase in the right middle cigulum gyrus, the right supplementary motor area and the left thalamus. ConclusionsThese findings highlight the need to understand the fundamental neural network dysfunction in SUDEP, which may fill the missing link between seizure-related cardiorespiratory dysfunction and SUDEP, and provide a promising neuroimaging biomarker for risk prediction of SUDEP.
ObjectiveTo systematically evaluate pharmacoeconomic studies on Programmed cell death-1/Programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors for advanced gastric cancer (GC) globally, providing evidence for healthcare policy formulation and clinical decision-making. MethodsWe conducted electronic searches in PubMed, Cochrane Library, Web of Science, ScienceDirect, Embase, CNKI, WanFang Data, and VIP databases, retrieving relevant literature published from inception to February 2025. Two researchers independently screened the literature, extracted data, and assessed study quality using the CHEERS 2022 checklist. We systematically summarized and analyzed the basic characteristics, model structures, methodological approaches, and economic outcomes of the included studies through inductive analysis. ResultsA total of 15 studies were included, with overall good quality. All included studies employed cost-utility analyses, among which 9 utilized partitioned survival models and 6 adopted Markov models. Direct medical costs were used as the cost calculation basis in all studies. Economic evaluations showed that most PD-1/PD-L1 inhibitors combined with chemotherapy were not cost-effective compared with chemotherapy alone. However, in patients with high PD-L1 expression, PD-1/PD-L1 inhibitor-based combination therapy demonstrated cost-effectiveness for advanced gastric cancer treatment. ConclusionThe economic viability of PD-1/PD-L1 inhibitor-based combination therapy for advanced GC varies significantly across regions due to drug pricing, economic status, and national contexts. Although most current regimens are not cost-effective, their clinical efficacy advantages suggest substantial future potential. Reducing drug prices is recommended to enhance drug accessibility in China.
ObjectiveTo investigate the effects of lenvatinib combined with transarterial chemoembolization (TACE) and programmed death protein-1 (PD-1) monoclonal antibody (Abbreviated as LEN-TAP regimen) on residual liver volume and surgical safety in intermediate and advanced hepatocellular carcinoma (HCC). MethodsThe clinicopathologic data of patients with intermediate and advanced HCC were collected retrospectively, who underwent the LEN-TAP conversion therapy and surgical resection in the Department of Liver Surgery, West China Hospital, Sichuan University from October 2020 to December 2021. The total liver volume, tumor volume, and residual liver volume of the patients before and after conversion therapy were analyzed. ResultsA total of 48 patients were included, 26 of whom had partial remission and 22 had stable disease, the objective response rate was 54.2% (26/48) according to the Response Evaluation Criteria in Solid Tumours 1.1 after conversion therapy. Before and after conversion therapy, the total liver volumes including tumor were (1 607.15±712.22) mL and (1 558.03±573.89) mL [mean difference (MD) and 95% confidence interval (CI)=–57.42(–134.30, 19.46), t=–1.503, P=0.140], the total liver volumes excluding tumor tissue were (1 095.28±227.60) mL and (1 260.31±270.71) mL [MD(95%CI)=165.03(128.13, 201.93), t=8.997, P<0.001], the tumor volumes were 260.25(107.75, 699.50) mL and 121.73 (33.00, 332.88) mL [MD(95%CI)=–222.45(–296.46, –148.44), Z=–5.641, P<0.001], and the residual liver volumes were (493.62±154.51) mL and (567.83±172.23) mL [MD(95%CI)=74.21(54.64, 93.79), t=7.627, P<0.001], respectively. The increase rates of tumor volume and residual liver volume after conversion therapy were (–53.34±33.05)% and (16.34±15.16)%, respectively. The conversional resections were successfully completed in all patients, with 13 (27.1%) cases experiencing postoperative complications and without occurrence of postoperative liver failure. ConclusionThe data analysis results of this study indicate that the LEN-TAP conversion therapy can shrink tumor volume and increase the residual liver volume for patients with intermediate and advanced HCC, which helps to improve the safety of conversion resection.
Cancer is a heterogeneous disease characterized by maladjustment of cell death. The types of cell death were mainly divided into two forms including accidental cell death and regulated cell death (RCD). In recent years, researchers have discovered dozens of RCD modes, among which apoptosis, pyroptosis, necroptosis, and ferroptosis are the most widely studied. Cuproptosis is a new cell death mechanism that first proposed on 17 March 2022. It is recognized as a unique and both copper and mitochondria dependent RCD. The research and development of targeted drugs for regulating different cell death pathways will be hots and difficulties in the treatment of refractory cancer in the future.
ObjectiveTo evaluate the protective effect of estrogen on survival of retinal ganglion cells (RGCs) after transient retinal ischemia-reperfusion (RIR) in rats.MethodsRIR was induced in 60 ovariectomized adult rats (OVX) by increasing intraocular pressure via an intracameral catheter. All of the rats were divided into two groups randomly: in experimental group, the rats underwent a subcutaneous injection with 17β-estrodiol（100 μg/kg） 2 hours before retinal ischemia; and in the control group, saline water was injected correspondingly. The number of RGCs and the thickness of the inner retinal layers were mesured by HE staining method before and 12, 24, 48, and 72 hours after reperfusion. TdT-mediated biotin-dUTP nick end labelling (TUNEL) staining technique was used to examine the apoptosis of RGCs.ResultsTwenty-four and 48 hours after reperfusion, the number of apoptotic cells in experimental group was obvious lower than that in the control group(Plt;0.05), and the number of RGCs in experimental group was higher than that in the control group(Plt;0.05).ConclusionEstrogen can protect retinal neurons from transient RIR in ovariectomized rats.(Chin J Ocul Fundus Dis, 2005,21:177-179)