ObjectiveTo investigate the effects of Huanglian Jiedutang （HLJDT） on cognitive function in mice with ischemic stroke （IS） and to elucidate whether its neuroprotective effects are mediated by inhibition of the nuclear factor-κB （NF-κB） signaling pathway and subsequent suppression of NF-κB-regulated neuronal apoptosis. MethodsAn IS model was established using middle cerebral artery occlusion （MCAO）. Sixty C57BL/6J mice were randomly assigned to five groups （n =12 per group）， i.e.， sham operation， model， HLJDT low-dose （3.9 g·kg^-1·d^-1）， HLJDT high-dose （7.8 g·kg^-1·d^-1）， and Ginkgo biloba extract （GBE， 31.2 mg·kg^-1·d^-1）. Post-operatively， neurological deficit scores （Longa score）， cerebral infarct volume assessed by 2，3，5-triphenyltetrazolium chloride （TTC） staining， and brain water content were evaluated. Learning and memory were assessed using new object recognition （NOR） and fear conditioning （FC） tests. Hippocampal pathology was examined via hematoxylin and eosin （HE） staining. Immunofluorescence detected expression of glial fibrillary acidic protein （GFAP， astrocyte marker）， cellular oncogene Fos （c-Fos， neuronal activation marker）， and glutamate decarboxylase 65 （GAD65）. Western blot measured nuclear factor-κB inhibitor protein α （IκBα）， phosphorylated IκBα （p-IκBα）， NF-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， ionic calcium binding adapter molecule 1 （Iba-1）， tumor necrosis factor （TNF）-α， interleukin （IL）-1β， and apoptosis-related proteins， such as cleaved cysteinyl aspartate-specific protease 3 （Caspase-3）， B-cell lymphoma 2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. Real-time quantitative PCR （Real-time PCR） was used to assess mRNA levels of Iba-1， TNF-α， IL-1β， NF-κB p65， cleaved Caspase-3， Bax， and Bcl-2. ResultsCompared with the sham group， the model group exhibited significantly increased neurological deficit scores， brain water content， and cerebral infarct volume （P<0.01）. Hippocampal CA1 neurons were disorganized， showing nuclear pyknosis and karyolysis. NOR exploration time and FC freezing time were significantly reduced （P<0.01）. GFAP and c-Fos expression were increased， while GAD65 expression was decreased （P<0.01）. Cleaved Caspase-3 and Bax were upregulated， Bcl-2 was downregulated， and the Bax/Bcl-2 ratio was elevated （P<0.01）. Expression levels of p-IκBα， p-NF-κB p65， IL-1β， TNF-α， and Iba-1 were significantly increased （P<0.01）. Compared with the model group， HLJDT high-dose， low-dose， and GBE groups showed significant improvements in all parameters （P<0.01）. Among them， the HLJDT high-dose group showed the most pronounced neuronal structural recovery and superior performance in NOR and FC tests （P<0.01）. In this group， GFAP and c-Fos decreased， GAD65 increased （P<0.01）， apoptosis-related protein expression was reversed， and NF-κB signaling and related inflammatory factor expression were suppressed （P<0.01）. ConclusionHLJDT ameliorates cognitive dysfunction in mice after IS， potentially by inhibiting the NF-κB signaling pathway， thereby reducing neuroinflammation and hippocampal neuronal apoptosis.

To report diagnosis and treatment of a patient with rectal cancer and synchronous liver metastases, accompanied by severe coronary artery stenosis and cardiac insufficiency, and to provide a reference for clinical decision-making in such cases through introducing the treatment contradiction, the choice of systemic treatment plan and the timing of operation, and the final outcome. After definitive diagnosis, the patient received systemic therapy with cetuximab＋irinotecan＋oxaliplatin＋raltitrexed, and along with oral medication to improve cardiac function, followed by elective coronary revascularization. After revascularization, the cardiac function of patient was fully improved. And the tumor lesion was effectively controlled after antitumor therapy. Once the cardiac condition of patient stabilized, two-stage surgical resection of the primary rectal cancer and liver metastases was performed, ultimately achieving tumor-free status, and discharged.

ObjectiveTo observe and compare the effects of different concentrations of cyclophosphamide (CTX) in inducing premature ovarian insufficiency (POI) model in mice and investigate the mechanism of injury. MethodsThirty-two 6~8-week-old female C57BL/6J mice were randomly divided into four groups (n=8 per group) using a weight-based block randomization method. The POI model was established via a single intraperitoneal injection of 75 mg/kg cyclophosphamide (CTX), 120 mg/kg CTX, 120 mg/kg CTX + 12 mg/kg Busulfan, or an equivalent volume of normal saline (control). Ovarian coefficients, serum estradiol (E₂) and follicle-stimulating hormone (FSH) levels were measured. Western blotting was performed to assess changes in ovarian expression levels of NAD-dependent deacetylase sirtuin-5 (SIRT5) and forkhead box O3a (FOXO3a) under different modeling conditions. After determining the optimal CTX concentration for modeling, an additional forty 6~8-week-old femal C57BL/6J mice were randomly divided into five groups (n=8 per group) using a weight-based block randomization method: saline control, 120 mg/kg CTX sampling at 1, 2, 7, or 14 days after modeling. Western blotting was used to evaluate temporal changes of ovarian SIRT5 and FOXO3a protein expression. ResultsCompared with the saline control, all concentrations of CTX (75 mg/kg CTX, 120 mg/kg CTX) and 120 mg/kg CTX + 12 mg/kg Busulfan induced POI injury in mice. The 120 mg/kg CTX group exhibited smaller changes in ovarian coefficients (P<0.001) and E₂ levels (P<0.05), whereas the 120 mg/kg CTX + 12 mg/kg Busulfan group showed rough and reduced luster fur, sluggish response and was in the worst state. Compared with the saline control group, FOXO3a expression was significantly down-regulated (P<0.05), while SIRT5 remained unchanged in the 75 mg/kg CTX group (P>0.05). In contrast, both SIRT5 (P<0.05) and FOXO3a (P<0.05) were significantly down-regulated in the 120 mg/kg CTX group. Further analysis revealed that on day 2 and 7 after 120 mg/kg CTX modeling, the expressions of SIRT5 (P<0.01) and FOXO3a (P<0.001) were significantly down-regulated, with the largest decrease observed on day 7 (SIRT5, P<0.000 1; FOXO3a, P<0.000 1). ConclusionOvarian injury in the POI model induced by 120 mg/kg CTX is milder than that in the POI model induced by 75 mg/kg CTX. Moreover, the expression changes of SIRT5 and FOXO3a are most significant on day 7 after modeling induced by 120 mg/kg CTX, which may be related to the inhibition of the SIRT5-FOXO3a signaling pathway.

Objective To develop a risk assessment scale for immune checkpoint inhibitor (ICI)-associated myocarditis based on multidisciplinary collaboration, and to evaluate its diagnostic performance. Methods Based on multidisciplinary cooperation, integrating clinical experience from oncology and cardiology, literature data, and patient conditions, a risk assessment scale for ICI-associated myocarditis was developed. A total of 101 patients with malignancies who received immunotherapy at Zhongshan Hospital, Fudan University, from October 2020 to October 2024 were included as the validation cohort. Patients were stratified into low-risk (0-1 point), medium-risk (2-4 points), and high-risk (≥5 points) groups based on their scale scores. The association between pretictive risk stratifications and actual assessment results was assessed using the Cox proportional hazards regression model. The predictive value of the scale for ICI-associated myocarditis was evaluated using receiver operating characteristic (ROC) curve. Agreement between the scale scores and actual assessment results was assessed using Cohen’s Kappa coefficient. Results Based on the scale pretictive results, 28(27.7%), 8(7.9%), 65(64.4%) patients were at low risk, medium risk, and high risk for ICI-related myocarditis, respectively; however, 46(45.5%), 8(7.9%), 47(46.5%) were at low risk, medium risk, and high risk actually. Kaplan-Meier survival analysis showed that the cumulative incidence of ICI-related myocarditis in the high-risk group was significantly higher than that in the medium- and low-risk groups (P＜0.05). In the multivariable-adjusted Cox proportional hazards model, the ICI-related myocarditis risk in high-risk group was about 4 times that in the low-risk group. ROC curve analysis demonstrated that the average area under the curve (AUC) for predicting ICI-related myocarditis was 0.81, with an accuracy of 0.74. The Cohen’s Kappa coefficient was 0.55, indicating moderate agreement. In the actual high-risk group, no patient was predicted to be at low risk; in the actual low-risk group, 16 patients were predicted to be at high risk. Conclusions This risk assessment scale for ICI-associated myocarditis shows high predictive performance. It provides oncologists with a simple yet effective multidisciplinary diagnostic reference tool, potentially enhancing early identification of ICI-associated myocarditis.

ObjectiveTo analyze the impact of maternal postpartum depression (PPD) at 2 months postpartum on caregiving for infants aged2 to 24 months, and to provide a scientific basis for future maternal and infant healthcare services. MethodsBased on the Shanghai Maternal-Child Pairs Cohort, 1 060 mother-child pairs were selected from those fully participating in follow-up visits at 2, 6, 12, and 24 months postpartum. Pregnancy and childbirth-related information was collected using standardized questionnaire surveys and hospital obstetric and maternity records. The Edinburgh postpartum depression scale was used to assess the maternal postpartum depressive symptoms at 2 months postpartum. At 2, 6, 12, and 24 months postpartum, questionnaire survey was used to evaluate the maternal responsiveness in caregiving and the provision of early learning opportunities for infants. Scores for responsive caregiving and early learning opportunities at 2, 6, 12, and 24 months were grouped based on the 25th percentile (P₂₅) of total scores. The mixed-effects model was used to analyze the longitudinal impact of maternal postpartum depression at 2 months on the caregiving of 2 to 24-month-old infants. ResultsThe longitudinal results from the mixed-effects model did not show an impact of maternal PPD on infant responsive caregiving within 12 months and early learning opportunities within24 months. However, cross-sectional analysis revealed that, compared to the non-PPD group, the risk of low responsive caregiving at 2 months in the PPD group was 93% higher (OR=1.931, 95%CI: 1.113‒3.364, P=0.019). The risks for low provision of early learning opportunities at2 months and 24 months increased by 59% (OR=1.589, 95%CI: 1.082‒2.324, P=0.017) and 60% (OR=1.598, 95%CI:1.120‒2.279, P=0.010), respectively. ConclusionMaternal postpartum depression increases the risk of low responsive caregiving at 2 months, but its long-term effects warrant further research.

AIM: To analyze the changes of retinal structure and function before and after panretinal photocoagulation(PRP)in patients with proliferative diabetic retinopathy(PDR).METHODS: Prospective study. Totally 98 cases(98 eyes)of PDR patients who underwent PRP in Eye Hospital of Wenzhou Medical University from January 2022 to May 2023 were included. Optical coherence tomography angiography(OCTA)was used to detect central retinal thickness(CRT), central macular thickness(CMT), subfoveal choroidal thickness(SFCT), foveal avascular zone(FAZ), deep vascular complex(DVC)blood flow density, superficial vascular complex(SVC)blood flow density before and at 1 wk, 1 and 3 mo after PRP. During the follow-up, 1 eye underwent vitrectomy, 2 eyes were lost to follow-up, and finally 95 eyes completed 1 a follow-up, with a loss rate of 3%. According to the visual prognosis at 1 a after treatment, the patients were divided into two groups: 73 eyes in good prognosis group and 22 eyes in poor prognosis group(including 9 eyes of visual disability and 13 eyes of visual regression). The changes in retinal structure and function before and after PRP treatment were compared between the two groups of patients, and the receiver operating characteristic(ROC)curve and decision curve were used to analyze the predictive value of retinal structure and function for PDR treatment.RESULTS: There were statistical significant differences in PDR staging, CRT, CMT, SFCT, DVC blood flow density, and SVC blood flow density between the two groups of patients before treatment(all P<0.05). At 1 wk, 1 and 3 mo after treatment, the FAZ area of both groups decreased compared to before treatment, while the blood flow density of DVC and SVC increased compared to before treatment(both P<0.05). However, there was no significant difference in the blood flow density of FAZ, DVC, and SVC between the two groups at 1 wk, 1 and 3 mo after treatment(all P>0.05). The CRT, CMT and SFCT of the two groups at 1 wk after treatment were higher than those before treatment(all P<0.05), but there were no significant differences between the two groups(all P>0.05). The CRT, CMT and SFCT at 1 and 3 mo after treatment were lower than those at 1 wk after treatment and before treatment in both groups. The CRT, CMT and SFCT in the poor prognosis group at 3 mo after treatment were higher than those at 1 mo after treatment, and were higher than those in the good prognosis group(all P<0.05). ROC analysis showed that, at 3 mo after laser treatment in PDR patients, the area under the curve of the CRT, CMT, and SFCT alone or in combination after treatment for 1 a was 0.788, 0.781, 0.783, and 0.902, respectively, and the combined prediction value was better(P<0.05). Decision curve analysis showed that the combined detection of CRT, CMT, and SFCT in PDR patients at 3 mo after treatment can improve the predictive value of visual prognosis.CONCLUSION: The optimal time for retinal structure and function recovery in PDR patients after PRP treatment is between 1 wk and 1 mo. OCTA measurement of CRT, CMT, and SFCT at 3 mo after treatment can predict the visual prognosis during the 1 a treatment period.

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Objective To investigate the improvement effect of Necrostatin-1 (Nec-1) on mouse models with immune checkpoint inhibitor (ICI) -associated myocarditis (ICIAM) and potential mechanism. Methods Ten male BALB/c mice aged 6-8 weeks were selected to construct the ICIAM models. The echocardiography and serum myocardial injury markers were used to assess cardiac function of mice. The levels of inflammatory markers including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Hematoxylin-eosin (HE) staining was used to evaluate myocardial inflammation, and Masson staining was used to evaluate myocardial fibrosis. The expressions of myocardial necroptosis proteins including receptor-interacting protein kinase 1 (RIP1), RIP3, mixed lineage kinase domain-like protein (MLKL) and their phosphorylated forms were detected by Western blotting. The spleen lymphocytes were extracted and co-cultured with HL-1 cell line. Cell viability was measured by cell counting kit-8 (CCK-8). The release of reactive oxygen species (ROS) and changes of mitochondrial membrane potential were observed. RIP1, RIP3, MLKL and their phosphorylated forms were determined. The levels of markers of oxidative stress, including malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), were measured. Results Nec-1 significantly improved the cardiac function injury of mice induced by ICI, and inhibited the release of TNF-α and IL-1β in plasma of ICIAM mice (P＜0.001); inhibited expressions of phosphorylated RIP1, RIP3 and MLKL (P＜0.05); decreased MDA activity, and increased SOD and GSH-Px activity (P＜0.001). In HL-1 cells, Nec-1 intervention inhibited the RIP1-RIP3-MLKL pathway (P＜0.05), improved decrease of the cell viability induced by lymphocytes (P＜0.001), decreased ROS release, increased mitochondrial membrane potential, inhibited MDA activity, and increased SOD and GSH-Px activities (P＜0.001). Conclusions Necroptosis plays an important role in the occurrence and development of ICIAM，but Nec-1 could alleviate the progression of ICIAM by inhibiting necroptosis induced by oxidative stress in cardiomyocytes; RIP1 maybe a new target in treatment of ICIAM.

The occurrence and development of colitis associated cancer(CAC)is closely related to the intestinal microenvironment.Traditional Chinese medicine(TCM)posits that"spleen deficiency"is the basic pathogenesis of colon cancer occurrence and development,and plays a key role in the process of"inflammation-cancer transformation".However,at present,the pathogenesis of spleen in the course of its pathogenesis is mostly focused on the body's own system,and few are discussed in combination with the theoretical basis of TCM's holistic view of"correspondence between man and nature".The spleen,as a taiyin organ with a damp-earth nature,relies on yang energy for movement,inherently averses dampness,and governs ascending qi.Late summer is mainly wet,which can easily obstruct the spleen qi,curb the upward trend and stop the spread opportunity when the wettability sticks and has a downward trend.This suggests that the influence of external environmental factors on the body should be comprehensively considered in the study of the classical process of"intestinal flora disturbance-inflammatory microenvironment formation-tumor formation"experienced in the pathogenesis of CAC.Based on the complementarity,mutual penetration and mutual promotion of the theories of traditional Chinese and western medicine,this paper discusses the role of external environmental factors in the occurrence of CAC focused on the mechanism of macrophage polarization imbalance during the formation of tumor inflammatory microenvironment,and provides a basis for the theoretical integration and development of TCM"time-dependent treatment"prevention and treatment strategies.

Isocitrate dehydrogenase(IDH)wild-type glioma is a type of highly invasive brain tumor with poor prognosis and a high recur-rence rate.The recurrence process is driven by multiple complex and interwoven factors.Although the current standard treatment regi-mens can temporarily alleviate patients'symptoms,they still face significant challenges in effectively preventing tumor recurrence.The re-currence mechanism of this tumor is intricate and covers multiple aspects such as genomic instability,maintenance of stem cell characterist-ics and mesenchymal transformation,as well as dynamic changes in the tumor microenvironment.This article aims to comprehensively sum-marize the recurrence mechanism of glioblastoma and deeply explore potential countermeasures targeting these mechanisms,hoping to open up new perspectives and approaches for the treatment of recurrent tumors.