AIM: To investigate the correlation between serum Sestrin 2(SESN2), signal peptide, CUB and EGF-like domain-containing protein 1(SCUBE-1), and longpentraxin 3(PTX3)levels, with disease severity and prognosis in patients with diabetes macular edema(DME). METHODS:Prospective study. The study included DME patients who were treated at the hospital between January 2023 and October 2024, as well as patients with type 2 diabetes mellitus(T2DM)and healthy individuals who underwent physical examinations during the same period. Serum levels of SESN2, SCUBE-1, and PTX3 were measured using the ELISA method. Factors influencing poor prognosis in DME patients were analyzed. RESULTS:This study included a total of 114 eye from 114 DME patients, For unilateral disease, the affected eye was enrolled; for bilateral disease, the more severely affected eye was selected for enrollment.(72 men and 42 women, with a mean age of 56.94±7.38 y), 114 T2DM patients(65 men, 49 women, mean age 56.18±7.22 y), and 114 healthy individuals(77 men, 37 women, mean age 56.33±7.26 y). There were no cases of loss to follow-up. FPG and HbA1c levels in the DME and T2DM groups were significantly higher than those in the healthy group(all P<0.05). Serum SESN2 levels decreased progressively from the healthy group to the T2DM group to the DME group, while SCUBE-1 and PTX3 levels increased progressively(all P<0.05). DME patients were classified by disease severity into a mild group of 23 cases(14 men, 9 women, mean age 55.81±7.52 y), a moderate group 54 cases(35 males, 19 females, mean age 56.97±7.35y), and a severe group 37 cases(23 males, 14 females, mean age 57.60±7.41 y). Serum SESN2 levels decreased progressively from the mild to the moderate and to the severe group, while SCUBE-1, PTX3, and CST levels increased progressively(all P<0.05). Serum SESN2 levels were negatively correlated with DME severity and CST, whereas SCUBE-1 and PTX3 levels were positively correlated with both DME severity and CST(all P<0.001). Among the 114 DME patients, 81 were in the favorable prognosis group and 33 were in the unfavorable prognosis group. In the poor prognosis group, serum SESN2 levels were lower than those in the favorable prognosis group, while SCUBE-1 and PTX3 levels were higher(all P<0.05). Low serum SESN2 levels, high SCUBE-1 levels, and high PTX3 levels were factors associated with poor prognosis in DME patients(all P<0.05). The AUC(0.916)for the combined prediction of poor prognosis in DME patients using serum SESN2, SCUBE-1, and PTX3 levels was higher than that for each marker individually(0.780, 0.782, and 0.783, respectively, all P<0.05). CONCLUSION:Serum SESN2 levels are reduced in DME patients, while SCUBE-1 and PTX3 levels are elevated. Changes in these three markers are associated with disease severity and prognosis, and the combined detection has high predictive value for poor patient outcomes.

Synovial sarcoma is a soft tissue malignancy of unknown origin which usually occurs around the joints of the extremities, but rarely detected in the kidneys. A case of primary synovial sarcoma of the kidney was reported, which was preoperatively diagnosed as a malignant tumor of the right kidney for intermittent gross hematuria. After the laparoscopic radical nephrectomy, primary renal synovial sarcoma was confirmed by pathological examination. The patient refused further treatment, and there was no recurrence or metastasis during the 13 months of follow-up.

BACKGROUND: Epidermal growth factor receptor (EGFR) and cellular-mesenchymal to epithelial transition factor (c-Met) are widely expressed on cancer cells. There is a synergistic effect of EGFR and HGF/c-Met pathways on proliferation, downstream activation of signal transduction and an additive effect. Studies show that combination of both signaling pathways could potentially be targeted in a synergistic fashion. Amivantamab, a bispecific monoclonal antibody targeting EGFR and c-Met, yielded robust and durable responses in a variety of clinicals trials. However, few researches have reported its efficacy in Chinese non-small cell lung cancer (NSCLC) patients. This study was conducted to evaluate the effectiveness and tolerance of Amivantamab in NSCLC patients with EGFR/MET gene abnormalities at Peking University Cancer Hospital. METHODS: The study enrolled NSCLC patients who received Amivantamab in our hospital between August 2020 and December 2021, and analyzed the response, survival, and treatment-related adverse events. RESULTS: Fifteen patients were enrolled in this research, and six of them received Amivantamab treatment and the other nine patients received Amivantamab plus Lazertinib treatment. The rates of partial response (PR), stable disease (SD), and progressive disease (PD) were 46.7% (7/15), 46.7% (7/15) and 6.7% (1/15), respectively. The overall response rate (ORR) and disease control rate (DCR) were 28.6% (2/7) and 100.0% (7/7) in seven patients with EGFR exon 20 insertion, respectively. The ORR and DCR were 40.0% (2/5) and 100.0% (5/5) in five post-osimertinib EGFR-mutant patients, respectively. After a median follow-up of 8.7 months, the median progression-free survival and overall survival were not reached. The most common treatment-related adverse events were rash (86.7%), paronychia (80.0%), and infusion-related reactions (60.0%), and most of them were graded as 1 to 2. Grade 3 to 4 adverse events included rash (33.3%), alanine aminotransferase elevation (13.3%), gamma-glutamyl transpeptidase elevation (13.3%), peripheral edema (6.7%), thromboembolism (6.7%), interstitial lung disease (6.7%), and thrombocytopenia (6.7%). CONCLUSIONS Amivantamab was effective in Chinese NSCLC patients with EGFR exon 20 insertion and post-Osimertinib EGFR-mutant patients, similar to the results of clinical trials conducted in western countries. Amivantamab was well tolerated and emphases should be put on adverse events such as rash, paronychia, and infusion-related reactions.
Antibodies, Bispecific ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Exanthema/drug therapy* ; Humans ; Lung Neoplasms/genetics* ; Mutation ; Paronychia/drug therapy* ; Protein Kinase Inhibitors/therapeutic use*

Objective To compare the effects of spinal anesthesia and general anesthesia on early postoperative cognitive function in elderly patients undergoing hip replacement.Methods One hundred and four elderly patients of both sexes,aged ≥ 60 yr,with body mass index of 18.5-24.0 kg/m2,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective unilateral hip replacement,were randomized into 2 groups (n =52 each) using a random number table method:general anesthesia group (group G) and spinal anesthesia group (group S).Total intravenous general anesthesia was adopted to maintain the bispectral index value at 40-60 during surgery in group G.In group S,spinal anesthesia was applied by injecting 0.5％ bupivacaine 1.5-3.0 ml at the L3-4 vertebral interspace,and the level of anesthesia was regulated and maintained at T10.Mini-Mental State Examination scale was used to evaluate the cognitive function on 1 day before surgery (T0) and 7 days after surgery (T,).Difference value method,1 standard deviation method and Z score method were applied to diagnose postoperative cognitive dysfunction.Patients' spouses in two groups were recruited as control group (group C) according to the Z-scoring method.Results There were 47 and 49 cases in G and S groups,respectively,and 33 cases in group C.Compared with group C,the memory score was significantly decreased at T1 (P＜0.01),and no significant change was found in group S (P＞0.05).The memory score was significantly higher at T1in group S than in group G (P＜0.01).There were no significant differences in the incidence of postoperative cognitive dysfunction between group G and group S (P＞0.05).Conclusion Spinal anesthesia and general anesthesia exerts no effect on early postoperative cognitive function in elderly patients undergoing hip replacement.

Chemotherapy is among the limited choices approved for the treatment of hepatocellular carcinoma (HCC) at intermediate and advanced stages. Preferential and prolonged drug exposure in diseased sites is required to maximize the therapeutic index of the drug. Here, we report an injectable supramolecular peptide hydrogel as an intraperitoneal depot for localized and sustained release of triptolide for the treatment of orthotopic HCC. We chose peptide amphiphile C-GNNQQNYKD-OH-based nanofibers as gelators and carriers for triptolide. Sustained triptolide release from the hydrogel was achieved over 14 days , with higher accumulation in and cytotoxicity against human HCC Bel-7402 in comparison with L-02 fetal hepatocytes. After intraperitoneal injection, the hydrogel showed prolonged retention over 13 days and preferential accumulation in the liver, realizing HCC growth inhibition by 99.7 ± 0.1% and animal median survival extension from 19 to 43 days, without causing noticeable pathological changes in the major organs. These results demonstrate that injectable peptide hydrogel can be a potential carrier for localized chemotherapy of HCC.

Human APOBEC3G (hA3G) is a cytidine deaminase which inhibits HIV-1 replication. The HIV-1 accessory protein viral infectivity factor (Vif) counteracts with hA3G by targeting it for proteasomal degradation. In this work, we constructed and optimized molecular models of the hA3G dimer and the hA3G-Vif complex. The molecular modeling study revealed that the loop7 motif of hA3G appears on the interfaces of both the hA3G-Vif complex and the hA3G dimer. Biochemical analysis provided evidence suggesting that binding of Vif to hA3G results in steric blocking of hA3G dimerization, implying that monomeric hA3G serves as a substrate for Vif-mediated degradation. Furthermore, we presented evidence for the important roles of the loop7 motif, especially the central residues within the region, in hA3G dimerization, hA3G--Vif interaction, Vif-mediated hA3G degradation as well as subcellular localization of hA3G. This work highlights a multiple-task interface formed by loop7 motif, which regulates biological function of hA3G, thus providing the feasibility of the strategy of blocking Vif-mediated A3G degradation by targeting the putative site around loop7.

Objective Using middle cerebral artery occlusion (MCAO) model to observe protective effect of effective components of bezoar on brain damage.To discuss the anti-cerebral ischemia mechanism and compare the efficacy of effective components of bezoar from the endoplasmic reticulum stress intervention angle.Methods Rats were stratified randomly divided into sham group,model group,Qingkailing group (positive drug,3 mL/kg),taurine group,ursodeoxycholic acid (UDCA,78 mg/kg) group,taurine-conjugated ursodeoxycholic acid (TUDCA,100 mg/kg) group.Through establish MCAO model in rats,observed the scores of the neurologic impairment,measured infarct volume by TTC.Immunohistochemistry and Western blotting were Used to detect the content of P-PERK,P-EIF2α,and ATF4.Results Compared with sham group,neurologic impairment scores of model group significantly reduced (P ＜ 0.01).Compared with model group,Qingkailing group,UDCA group,and TUDCA group significantly improved neurological function in rats (P ＜ 0.05,0.01).Compared model group,all the treatment groups could significantly reduce the volume of cerebral infarction (P ＜ 0.01).Compared with sham group,expression of P-PERK,P-EIF2α,and ATF4 was significantly increased (P ＜ 0.01).Compared with model group,all the treatment groups reduced the expression of P-PERK,P-EIF2α,and ATF4 in varying degrees,effect of Qingkailing and TUDCA were more obvious.Conclusion The effective components ofbezoar alleviate cerebral ischemia reperfusion injury in rats by inhibiting endoplasmic reticulum stress,the effect of TUDCA is better than that of taurine and UDCA.

Objective To investigate clinical significance and related factors of fluid-attenuated inversion recov?ery vascular hyperintensities (FVH) in transient ischemic attack (TIA) of carotid system. Method Data including general information and TIA risk factors was continuously collected from 142 patients with carotid system TIA from the depart?ment of neurology of Sheng jing Hospital affiliated China Medical University from January 2012 to February 2014.All pa?tients completed brain MRI including FLAIR and diffusion-weighted imaging (DWI)and MRA examinations within 72 hours after TIA. All patients were followed up for one month. Risk factors and FVH situations were analyzed based on clinical manifestations and DWI results. Result There were 87 male cases (61.27%)and FVH positive 57 cases (40.14%) among 142 cases with carotid system TIA (mean age 63.2±11.5). Logistic regression analysis revealed that the large intra?cranial carotid artery stenosis≥50%(OR=2.44,95%CI:1.09~5.49, P=0.03) and prior history of ischemic stroke (OR=3.88,95%CI:1.04~14.5, P=0.04) were independently associated with positive FVH. At one month followed-up, 40 cas?es (28.17%) of 142 patients progressed to acute cerebral infarction. Vulnerable plaque number in the contralateral carot?id artery (P=0.018), contralateral intracranial large vessel stenosis in MRA≥50%(P=0.007) and contralateral FVH oc?currence rate (P=0.001) were significantly higher in cerebral infarction group than in non-cerebral infarction group. Con?clusion FVH is common in carotid TIA patients, which is associated with intracranial carotid artery stenosis ischemic and previous history of ischemic stroke. Vulnerable plaque number of contralateral carotid artery, contralateral intracranial large vessel stenosis≥50%and the rate of occurrence of contralateral FVH may be associated with short-term progress leading TIA to acute infarction.

Objective To evaluate whether MRI fluid attenuated inversion recovery (FLAIR)vascular hyperintensity (FVH) is an effective indicator for severe vascular stenosis or occlusion and disease severities in patients with acute anterior circulation infarction.Methods Three hundred and forty consecutive patients with acute anterior circulation infarction,admitted to our hospital from May 2013 to May 2014,were enrolled as subjects.All subjects were completed brain MR diffusion-weighted imaging (DWI),FLAIR and neck vascular or brain magnetic resonance angiography (MRA).According to the extent of FVH,all subjects were classified into negative FVH and positive FVH groups.Clinical data were obtained and compared among patients with different grades of FVH,and receiver operating characteristic (ROC) curve was used to calculate the sensitivity and specificity of FVH diagnosis of vascular severe stenosis or occlusion.The value of FVH in evaluating the disease severities of patients with large artery atherosclerosis combined with acute cerebral infarction according to new TOAST classification was evaluated.Results FVH was observed in 109 (32.06％) of the 340 patients.Significant differences were noted in the new TOAST classification ratio and vascular stenosis grading between the two groups; in the positive FVH group,the largest ratio was patients with large-artery atherosclerosis (82.6％),while that was patients with small vessel diseases (56.3％); the ratio of patients with severe vascular stenosis and occlusion in positive FVH patients was significantly higher than that in negative FVH patients (34.9％ vs.5.6％,39.5％ vs.0.9％).Spearman rank correlation analysis indicated that the degrees of vascular stenosis of carotid artery-middle cerebral artery were positively correlated to FVH (r=0.599,P=0.000).As compared with the negative FVH group,FVH patients had larger infarct volume and higher initial NIHSS scores (P＜0.05).ROC curve indicated that FVH had a sensitivity of 84.38％ and a specificity of 88.52％ in detecting artery stenosis (area under the curve [AUC]=0.892,95％ CI=0.85-0.94,P＜0.05),and a sensitivity of 88.89％ and a specificity of 85.76％ in detecting the vessel occlusion (AUC=0.929,95％CI:0.89-0.97,P＜0.05).In patients with acute cerebral infarction combined with artery atherosclerosis,patients with high FVH scores showed smaller infarct volumes and slighter neurological symptoms as compared with those with low FVH (P＜0.05).Conclusions FVH predicts vascular severe stenosis or occlusion with high sensitivity and specificity.In severe vascular stenosis or occlusion group,higher FVH scores are associated with lighter strokes.

Objective To observe the clinical curative effect of Depmas double blood purification system for acute severe organophosphorus pesticide poisoning.Methods Retrospectively study was carried out on 147 patients of acute severe organophosphorus pesticide poisoning.Patients were divided into four groups,the conventional treatment group treated with drug therapy,hemoperfusion group given HA230 hemoperfusion in addition to conventional treatment,plasma exchange combined with hemoperfusion group given HA230 hemoperfusion and plasma exchange therapy in addition to conventional treatment,and Depmas group treated with plasma separation by Baxter blood fiber and then given series HA230 and BS330 hemoperfusion treatment on the separated plasma in addition to conventional treatment.Survival rate,mean survival time of death patients,the concentration changes of cholinesterase and bilirubin in peripheral blood were observed.Results Compared to the conventional treatment group,survival rates of hemoperfusion group,hemoperfusion combined with plasma exchange group and Depmas group were higher,the mean survival time was longer,the cholinesterase concentration in peripheral blood was higher and the elevated bilirubin concentration was decreased with the differences statistically significant (P＜0.01).Compared to hemoperfusion group,the survival rates of hemoperfusion combined with plasma exchange group and Depmas group were higher,the mean survival time was longer,the cholinesterase concentration in peripheral blood were higher and the elevated bilirubin concentration was decreased with the differences statistically significant (P＜0.05).Besides,there were no significant differences between the survival rate,mean survival time,peripheral blood cholinesterase and bilirubin concentration of hemoperfusion combined with plasma exchange group and that of Depmas group (P＞0.05).Conclusions Depmas dual blood purification system has remarkable curative effect for the treatment of acute severe organophosphorus poisoning.