Aim To investigate the effects of tran-scription factor FoxO1 on acute kidney injury(AKI)induced by ischemic reperfusion injury(IRI)and to explore the underlying mechanisms.Methods Male C57BL/6 mice were randomly divided into four groups:Sham,IRI,FoxO1 inducible cell-specific knockout(FoxO1 icKO),and IRI+FoxO1 icKO.Tamoxifen(25 mg·kg-1)was intraperitoneally injec-ted to specifically knock out FoxO1 in mouse macro-phages,and a unilateral renal IRI model was estab-lished.The levels of serum creatinine(Scr),blood u-rea nitrogen(BUN),Fe2+,malondialdehyde(MDA),reactive oxygen species(ROS),and reduced glutathi-one(GSH)in renal tissues were detected.Hematoxy-lin-eosin(HE)staining was used to observe the patho-logical changes in renal tissues.Quantitative polymer-ase chain reaction(qPCR)was used to detect the mR-NA levels of inflammatory factors such as IL-1β and MCP1 in renal tissues.Western blot was used to detect the expression levels of apoptosis and ferroptosis-relat-ed proteins.Results Compared with the control group,the levels of Scr and BUN in the IRI group were significantly upregulated,the infiltration of inflammato-ry factors IL-1β,TNF-α and MCP1 increased,the pro-tein expressions of Bax/Bc12,cleaved-caspase-3/caspase-3,cytochrome C,and FTH1 in renal tissues were significantly enhanced,while the expression of GPX4 decreased.In addition,the levels of Fe2+,MDA and ROS in the renal cortex of the IRI group signifi-cantly increased,and the level of GSH markedly de-creased(P＜0.05).Compared with the IRI group,the levels of Scr and BUN in the FoxO1 icKO group were significantly reduced,the infiltration of inflammatory factors was alleviated,the expression of apoptosis-relat-ed proteins in renal tissue decreased,the expression level of ferroptosis protein GPX4 increased,and the ex-pression of FTH1 decreased.The levels of Fe2+,MDA and ROS in the renal cortex decreased,and the level of GSH significantly increased(P＜0.05).Conclusion Inducing the specific knockout of FoxO1 in macro-phages can alleviate AKI induced by IRI,and its mech-anism may be related to the inhibition of ferroptosis caused by IRI by FoxO1.

Aim To investigate the effects of tran-scription factor FoxO1 on acute kidney injury(AKI)induced by ischemic reperfusion injury(IRI)and to explore the underlying mechanisms.Methods Male C57BL/6 mice were randomly divided into four groups:Sham,IRI,FoxO1 inducible cell-specific knockout(FoxO1 icKO),and IRI+FoxO1 icKO.Tamoxifen(25 mg·kg-1)was intraperitoneally injec-ted to specifically knock out FoxO1 in mouse macro-phages,and a unilateral renal IRI model was estab-lished.The levels of serum creatinine(Scr),blood u-rea nitrogen(BUN),Fe2+,malondialdehyde(MDA),reactive oxygen species(ROS),and reduced glutathi-one(GSH)in renal tissues were detected.Hematoxy-lin-eosin(HE)staining was used to observe the patho-logical changes in renal tissues.Quantitative polymer-ase chain reaction(qPCR)was used to detect the mR-NA levels of inflammatory factors such as IL-1β and MCP1 in renal tissues.Western blot was used to detect the expression levels of apoptosis and ferroptosis-relat-ed proteins.Results Compared with the control group,the levels of Scr and BUN in the IRI group were significantly upregulated,the infiltration of inflammato-ry factors IL-1β,TNF-α and MCP1 increased,the pro-tein expressions of Bax/Bc12,cleaved-caspase-3/caspase-3,cytochrome C,and FTH1 in renal tissues were significantly enhanced,while the expression of GPX4 decreased.In addition,the levels of Fe2+,MDA and ROS in the renal cortex of the IRI group signifi-cantly increased,and the level of GSH markedly de-creased(P＜0.05).Compared with the IRI group,the levels of Scr and BUN in the FoxO1 icKO group were significantly reduced,the infiltration of inflammatory factors was alleviated,the expression of apoptosis-relat-ed proteins in renal tissue decreased,the expression level of ferroptosis protein GPX4 increased,and the ex-pression of FTH1 decreased.The levels of Fe2+,MDA and ROS in the renal cortex decreased,and the level of GSH significantly increased(P＜0.05).Conclusion Inducing the specific knockout of FoxO1 in macro-phages can alleviate AKI induced by IRI,and its mech-anism may be related to the inhibition of ferroptosis caused by IRI by FoxO1.

OBJECTIVES: To compare the effects of cell lysis method and magnetic beads method in forensic DNA identification and to explore these two methods in forensic DNA identification. METHODS: The genome DNA of THP-1 cells in different quantities was extracted by the cell lysis method and magnetic beads method, and the DNA content was quantified by real-time quantitative PCR. The cell lysis method and magnetic beads method were used to type the STR of human blood with different dilution ratios. RESULTS: When the numbers of THP-1 cell were 100, 400 and 800, the DNA content extracted by cell lysis method were (1.219±0.334), (5.081±0.335), (9.332±0.318) ng, respectively; and the DNA content extracted by magnetic beads method were (1.020±0.281), (3.634±0.482), (7.896±0.759) ng, respectively. When the numbers of THP-1 cells were 400 and 800, the DNA content extracted by the cell lysis method was higher than that by the magnetic beads method. The sensitivity of cell lysis method and magnetic beads method was similar in STR typing of human blood at different dilution ratios. Complete STR typing could be obtained at 100, 300 and 500-fold dilutions of blood samples, but could not be detected at 700-fold dilution. STR typing of undiluted human blood could not be detected by cell lysis method. CONCLUSIONS The cell lysis method is easy to operate and can retain template DNA to the maximum extend. It is expected to be suitable for trace blood evidence tests.
Humans ; Forensic Medicine ; DNA/genetics* ; Real-Time Polymerase Chain Reaction ; Magnetic Phenomena ; DNA Fingerprinting/methods* ; Microsatellite Repeats

Humans ; Fibrous Dysplasia, Polyostotic/complications* ; Hemangioma

Floaters are entopic phenomenon created by vitreous opacities. Some researchers term it as “symptomatic vitreous turbidity”, which usually refers to primary type in clinic. With the increasing prevalence and aging of myopia worldwide, vitreous floaters are becoming increasingly prevalent in clinics but receiving less attention. Floaters can impair patients' vision and quality of life due to their discomfort and disorientation. A few patients become intolerable and express a strong desire for treatment. YAG laser vitreolysis for floaters has garnered considerable attention in recent years. Although some doctors still have concerns about its efficacy and safety, a handful of studies have found some beneficial effects in recent years. The author has gained expertise in clinical practice in recent years. In this review, we talk about what causes floaters and how to classify them. We also talk about the clinical indications, how YAG laser ablation works, and whether or not it is safe.

AIM: To investigate the annual eye examination of diabetic patients in Shenyang and analyze the associated factors by using the Chinese version of the Compliance with Annual Diabetic Eye Exam Survey(CADEES)questionnaire.METHODS: This is a cross-sectional study. The diabetic patients who first visited Shenyang He Eye Specialist Hospital from November 2021 to October 2022 were collected. The Chinese version of the CADEES questionnaire was used to investigate the previous annual eye examinations of these patients, and no fundus examination in the past 1a was defined as poor participation. Factors associated with poor participation in annual eye examinations were identified by multivariate binary logistic regression analyses.RESULTS: A total of 468 patients were collected, including 192 males and 276 females, with an average age of 67.42±10.66 years. There were 330 patients without diabetic retinopathy(DR)and 138 patients with DR, among which 88 patients had vision-threatening diabetic retinopathy(VTDR)and 50 patients had non-vision-threatening diabetic retinopathy(NVTDR). 34.2%(160 cases)of patients had poor annual eye examination. The multivariate logistic regression analysis showed that, after controlling gender, age and other influencing factors, patients in rural area(OR=1.704, 95%CI: 1.019～2.850, P=0.042), VTDR(OR=1.948, 95%CI: 1.145～3.313, P=0.014), the item 7(I have felt blue, downhearted, or depressed over the past 4wk; OR=0.624, 95%CI: 0.401～0.971, P=0.037)and item 42(I receive a reminder from my eye doctor's office when it is time to schedule an exam; OR=0.618, 95%CI: 0.387～0.989, P=0.045)of CADEES questionnaire were risk factors for poor participation in the annual ophthalmic examination.CONCLUSIONS: Approximately one-third of diabetic patients in the Shenyang region may not follow the guidelines for DR annual eye examination. Healthcare providers should improve DR health education, increasing eye exam participation through necessary reminders.

AIM: To investigate the risk factors associated with neovascular glaucoma(NVG)after pars plana vitrectomy(PPV)for proliferative diabetic retinopathy(PDR).METHODS: The PDR patients who received 23G PPV treatment at Shenyang He Eye Specialist Hospital from October 2015 to September 2020 and were followed up for at least 12mo with complete data were retrospectively collected. The patients were divided into two groups according to the occurrence of NVG during follow-up. The preoperative and intraoperative variables between two groups were compared. The cumulative hazard ratio for NVG was evaluated. RESULTS: A total of 151 PDR patients(169 eyes)with a mean follow-up of 18.07±12.55(1～79)mo were included, of which 30(17.8%)eyes developed NVG, the mean time of occurrence was 6.27±4.01(1～17)mo, and 50%(15 eyes)of NVG occurred within 5mo after vitrectomy. The cumulative hazard ratios of NVG at postoperative 3, 6 and 12mo were 4.8%, 12.6% and 18.1%, respectively. Multivariate logistic regression analysis showed that preoperative best corrected visual acuity(OR=3.077, 95%CI: 1.203～7.869, P=0.019), preoperative iris rubeosis(OR=7.897, 95%CI: 1.313～47.498, P=0.024), and contralateral NVG(OR=22.108, 95%CI: 1.562～312.861, P=0.022)were risk factors with the occurrence of NVG, while the number of intraoperative retinal laser photocoagulation(OR=0.772, 95%CI: 0.666～0.893, P=0.001)was the protective factor with the occurrence of NVG.CONCLUSIONS: The incidence of NVG in PDR eyes after PPV was 17.8%, of which 50% occurred within 5mo after surgery. PDR eyes with poor baseline visual acuity, iris rubeosis, and contralateral NVG are prone to postoperative NVG, and sufficient intraoperative retinal laser photocoagulation has a certain protective effect. PDR eyes after PPV should be closely followed up for 1a.

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.
Humans ; East Asian People ; Neoplasms/pathology* ; Antibodies, Monoclonal, Humanized/therapeutic use*

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.
Humans ; East Asian People ; Neoplasms/pathology* ; Antibodies, Monoclonal, Humanized/therapeutic use*

Gut microbiome sequencing studies have great potential to translate microbial analysis outcomes into human health research. Sequencing strategies of 16S amplicon and whole-metagenome shotgun (WMS) are two main methods in microbiome research with respective advantages. However, how sample heterogeneity, sequencers and library preparation protocols affect the sequencing reproducibility of gut microbiome needs further investigation. This study aims to provide a reference for the selection of sequencing technologies by comparing differences in microbial composition from different sampling sites. The results of three widely adopted sequencers showed that the technical repetition correlation (r= 0. 94) was high in WMS method, while the biological repetition correlation (r = 0. 69) was low. Bray-Curtis distance identified that dissimilarity from biological replicates was larger than that of technical replicates (P<0. 001). In addition, dissimilarity and specific taxonomic profiles were observed between 16S and WMS datasets. Our results imply that homogenization is a necessary step before sample DNA extraction. The sequencers contributed less to taxonomic variation than the library preparation protocols. We developed an empirical Bayes approach that " borrowed information" in calculations and analyzed batch effect parameters using standardized data and prior distributions of (non-) parameters, which may improve population comparability between 16S and WMS and provide a basis for further application to fusion analysis of published 16S and microbial datasets.