Objective To investigate the effects of kaempferol on the oxidative damage and apoptosis of human lens epithelial cells induced by hydrogen peroxide(H2O2),as well as its regulatory role in the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway.Methods Human lens epithelial cells HLE-B3 were cultured in vitro and divided into the blank group(no intervention),the model group(400 pmol?L-1 H2O2),the kaempferol group(400 μmol?L-1 H2O2+40 pmol?L-1 kaempferol),the AG490 group(400 pmol?L-1 H2O2+50 μmol?L-1 JAK2/STAT3 signaling pathway inhibitor AG490),the inhibitor group(400 pmol?L-1 H2O2+40 pmol?L-1 kaempferol+50 μmol?L-1 AG490),and the activator group(400 pmol?L-1 H2O2+40 pmol?L-1 kaempferol+0.5 μmol?L-1 JAK2/STAT3 signaling pathway activator C-A1).After 24 h of intervention,Hoechst 33258 staining was used to determine the ap-optosis rate of these cells.Malondialdehyde(MDA)and superoxide dismutase(SOD)kits were used to detect the levels of MDA and SOD.The protein expression levels of Cysteine aspartic protease 3(Caspase-3),B-cell lymphoma-2(Bcl-2),JAK2,STAT3,p-JAK2,and p-STAT3 were detected by Western blot.Results Compared with the blank group,the apop-tosis rate,the MDA level,and the protein expression levels of Caspase-3,p-JAK2,and p-STAT3 increased(all P＜0.05)in the model group,while the protein expression levels of SOD and Bcl-2 decreased(all P＜0.05).Compared with the model group,the apoptosis rate,the MDA level,and the protein expression levels of Caspase-3,p-JAK2,and p-STAT3 decreased in the kaempferol and AG490 groups(all P＜0.05),while the protein expression levels of SOD and Bcl-2 increased(all P＜0.05).Compared with the kaempferol group,the apoptosis rate,the MDA level,and the protein expression levels of Caspase-3,p-JAK2,and p-STAT3 decreased in the inhibitor group,while the protein expression levels of SOD and Bcl-2 in-creased(all P＜0.05);the changes in the above indicators in the activator group were opposite to those in the inhibitor group(all P＜0.05).Conclusion Kaempferol can protect HLE-B3 cells from H2O2-induced oxidative damage and inhibit their apoptosis by inhibiting JAK2/STAT3 signaling pathway.

Objective To investigate the effects of kaempferol on the oxidative damage and apoptosis of human lens epithelial cells induced by hydrogen peroxide(H2O2),as well as its regulatory role in the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway.Methods Human lens epithelial cells HLE-B3 were cultured in vitro and divided into the blank group(no intervention),the model group(400 pmol?L-1 H2O2),the kaempferol group(400 μmol?L-1 H2O2+40 pmol?L-1 kaempferol),the AG490 group(400 pmol?L-1 H2O2+50 μmol?L-1 JAK2/STAT3 signaling pathway inhibitor AG490),the inhibitor group(400 pmol?L-1 H2O2+40 pmol?L-1 kaempferol+50 μmol?L-1 AG490),and the activator group(400 pmol?L-1 H2O2+40 pmol?L-1 kaempferol+0.5 μmol?L-1 JAK2/STAT3 signaling pathway activator C-A1).After 24 h of intervention,Hoechst 33258 staining was used to determine the ap-optosis rate of these cells.Malondialdehyde(MDA)and superoxide dismutase(SOD)kits were used to detect the levels of MDA and SOD.The protein expression levels of Cysteine aspartic protease 3(Caspase-3),B-cell lymphoma-2(Bcl-2),JAK2,STAT3,p-JAK2,and p-STAT3 were detected by Western blot.Results Compared with the blank group,the apop-tosis rate,the MDA level,and the protein expression levels of Caspase-3,p-JAK2,and p-STAT3 increased(all P＜0.05)in the model group,while the protein expression levels of SOD and Bcl-2 decreased(all P＜0.05).Compared with the model group,the apoptosis rate,the MDA level,and the protein expression levels of Caspase-3,p-JAK2,and p-STAT3 decreased in the kaempferol and AG490 groups(all P＜0.05),while the protein expression levels of SOD and Bcl-2 increased(all P＜0.05).Compared with the kaempferol group,the apoptosis rate,the MDA level,and the protein expression levels of Caspase-3,p-JAK2,and p-STAT3 decreased in the inhibitor group,while the protein expression levels of SOD and Bcl-2 in-creased(all P＜0.05);the changes in the above indicators in the activator group were opposite to those in the inhibitor group(all P＜0.05).Conclusion Kaempferol can protect HLE-B3 cells from H2O2-induced oxidative damage and inhibit their apoptosis by inhibiting JAK2/STAT3 signaling pathway.

Objective:To investigate the differences and similarities of parameters associated with ane-mia of inflammation between patients with stage Ⅲ periodontitis and periodontally healthy volunteers,and to explore the influence of periodontal initial therapy on those indicators.Methods:Patients with stageⅢ periodontitis and periodontally healthy volunteers seeking periodontal treatment or prophylaxis at De-partment of Periodontology,Peking University School and Hospital of Stomatology from February 2020 to February 2023 were enrolled.Their demographic characteristics,periodontal parameters(including pro-bing depth,clinical attachment loss,bleeding index),and fasting blood were gathered before periodontal initial therapy.Three months after periodontal initial therapy,the periodontal parameters of the patients with stage Ⅲ periodontitis were re-evaluated and their fasting blood was collected again.Blood routine examinations(including white blood cells,red blood cells,hemoglobin,packed cell volume,mean cor-puscular volume of erythrocytes,and mean corpuscular hemoglobin concentration)were performed.And ferritin,hepcidin,erythropoietin(EPO)were detected with enzyme-linked immunosorbent assay(ELISA).All data analysis was done with SPSS 21.0,independent sample t test,paired t test,and analysis of co-variance were used for comparison between the groups.Results:A total of 25 patients with stage Ⅲperiodontitis and 25 periodontally healthy volunteers were included in this study.The patients with stageⅢ periodontitis were significantly older than those in periodontally healthy status[(36.72±7.64)years vs.(31.44±7.52)years,P=0.017].The patients with stage Ⅲ periodontitis showed lower serum he-moglobin[(134.92±12.71)g/L vs.(146.52±12.51)g/L,P=0.002]and higher serum ferritin[(225.08±103.36)μg/L vs.(155.19±115.38)μg/L,P=0.029],EPO[(41.28±12.58)IU/L vs.(28.38±10.52)IU/L,P＜0.001],and hepcidin[(48.03±34.44)μg/L vs.(27.42±15.00)μg/L,P=0.009]compared with periodontally healthy volunteers.After adjusting the age with the co-variance analysis,these parameters(hemoglobin,ferritin,EPO,and hepcidin)showed the same trends as independent-sample t test with statistical significance.Three months after periodontal initial therapy,all the periodontal parameters showed statistically significant improvement.The serum hemoglobin raised[(146.05±15.48)g/L vs.(133.77±13.15)g/L,P＜0.001],while the serum ferritin[(128.52± 90.95)μg/Lvs.(221.22±102.15)μg/L,P＜0.001],EPO[(27.66±19.67)IU/L vs.(39.63± 12.48)IU/L,P=0.004],and hepcidin[(32.54±18.67)μg/L vs.(48.18±36.74)μg/L,P=0.033]decreased compared with baseline.Conclusion:Tendency of iron metabolism disorder and ane-mia of inflammation was observed in patients with stage Ⅲ periodontitis,which can be attenuated by periodontal initial therapy.

The lung is an important organ in systemic toxicity test of medical devices and is significant in safety evaluation. Based on the authors' understanding of medical devices, this study provides a brief analysis of the lung examination and common problems in systemic toxicity, so as to provide references for the pre-clinical safety evaluation of medical devices. It should be noted that a reasonable risk assessment should be made after comprehensive assessment for specific medical device products.
Equipment Safety ; Humans ; Lung ; Risk Assessment

Objective:To explore the role of transgelin(TAGLN) in the occurrence and development of papillary thyroid carcinoma (PTC) and its possible signal pathway.Methods:One hundred cases of PTC tissues and corresponding paracancerous normal thyroid tissues were collected. Realtime quantitative PCR (RT-qPCR), Western blotting, and immunohistochemistry were used to analyze the expression of TAGLN in PTC tissues and corresponding paracancerous normal thyroid tissues. PTC cells were transfected with plasmid and shRNA lentivirus vector respectively to up-regulate or down-regulate the expression of TAGLN in order to detect the effects of them on the proliferation, invasion, and migration by cell proliferation assay(cell counting kit-8, CCK-8)and cell invasion and migration assays (Transwell). The effects of TAGLN on mitogen-activated protein kinase (MAPK)/extracellular-signal regulating kinase (ERK) signal pathway was detected with Western blotting.Results:RT-qPCR showed that there was no difference in the expression of TAGLN mRNA between PTC and corresponding paracancerous normal thyroid tissues ( P>0.05); Western blotting demonstrated that the expression of TAGLN protein in PTC tissues was significantly lower than that in corresponding paracancerous normal thyroid tissues ( P<0.01). Immunohistochemical results revealed that the expression of TAGLN in PTC tissues was significantly lower than that in corresponding paracancerous normal thyroid tissues. Overexpression of TAGLN inhibited the proliferation, invasion, and migration of PTC cells ( P<0.01), but knockdown of TAGLN promoted the proliferation, invasion, and migration of PTC cells ( P<0.01). Overexpression of TAGLN decreased the expression of phosphorylated ERK ( P<0.05), whereas silencing TAGLN increased phosphorylated ERK level in PTC cells( P<0.01). Conclusion:The expression of TAGLN in PTC is significantly decreased. It is related to the occurrence and development of PTC, and its mechanism may be related to MAPK/ERK signal pathway.

The orbitofrontal cortex (OFC) is involved in diverse brain functions via its extensive projections to multiple target regions. There is a growing understanding of the overall outputs of the OFC at the population level, but reports of the projection patterns of individual OFC neurons across different cortical layers remain rare. Here, by combining neuronal sparse and bright labeling with a whole-brain florescence imaging system (fMOST), we obtained an uninterrupted three-dimensional whole-brain dataset and achieved the full morphological reconstruction of 25 OFC pyramidal neurons. We compared the whole-brain projection targets of these individual OFC neurons in different cortical layers as well as in the same cortical layer. We found cortical layer-dependent projections characterized by divergent patterns for information delivery. Our study not only provides a structural basis for understanding the principles of laminar organizations in the OFC, but also provides clues for future functional and behavioral studies on OFC pyramidal neurons.

Objective: To explore the clinical value of contrast-enhanced ultrasound combined with modified labeled method in labeling sentinel lymph nodes of breast cancer in comparison with nano-carbon stained method. Methods: Eighty female breast cancer patients who underwent surgery in the First Affiliated Hospital of Soochow University between July 2017 and April 2019 were enrolled. Sentinel lymph nodes in all patients were labeled by contrast-enhanced ultrasound combined with modified labeled method and nano-carbon stained method, respectively. The consistency of first lymph node labeled by the two methods was judged, the number of SLNs labeled by two methods was counted, and the pathology of the labeled SLN was compared with that after axillary dissection. Results: The two methods have good consistency in locating sentinel lymph nodes of breast cancer(Kappa=0.749, P=0.000). The number of SLNs labeled by modified labeling method was significantly less than that labeled by stained method(Z=-7.434, P=0.000). The pathology of lymph nodes labeled by both the modified labeling method and stained method coincided well with that of axillary dissection(Kappa=0.941, 0.943; P=0.000, 0.000), and diagnostic efficiency was comparable(AUC=0.964, 0.967). Conclusions Contrast-enhanced ultrasound combined with modified labeling method is simple and accurate in labeling sentinel lymph nodes of breast cancer. Accurate assessment of axillary lymph node staging can be made by precise biopsy of 1-2 SLNs.

OBJECTIVETo evaluate the safety and preliminary efficacy of dose-modified regimen of 5-fluorouracil plus oxaliplatin and irinotecan (mFOLFOXIRI) for patients with advanced colorectal cancer (CRC).

METHODSData of 312 CRC patients confirmed by pathology receiving triplet drug alone or combined with target therapy between October 2012 and December 2016 at the Sixth Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. CRC patients who had previously completed adjuvant therapy (or neoadjuvant therapy) within 6 months or palliative chemotherapy were excluded, meanwhile those with poor general condition (ECOG score > 2) or grade 2 neuropathy and allergy to oxaliplatin were excluded as well. Regimen of mFOLFOXIRI: oxaliplatin 85 mg/m² dissolved in 5% glucose solution 500 ml by intravenous infusion for 2 h; irinotecan 150 to 165 mg/m² dissolved in 0.9% sodium chloride 250 ml by intravenous infusion for 90 min; following intravenous infusion of leucovorin 400 mg/m² for 2 h, day 1; 5-FU 2800 mg/m², 48-h continuous intravenous infusion; once every 2 weeks. Therapy could be combined with a targeted drug, bevacizumab 5 mg/kg every two weeks; cetuximab 500 mg/m² every two weeks. Side effect was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE 4.0.3). The objective response rate was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) after administering at least four cycles of chemotherapy.

RESULTSThe median age was 52 years (range 16-73) in the whole group; 113 patients (36.2%) had locally advanced CRC, and 199 (63.8%) had metastatic CRC. Most patients (274/312, 87.8%) did not receive any treatment earlier. There were a total of 1651 chemotherapy cycles in the whole group, with a median of 6(1-19) cycles. Of these 1651 cycles, 124 cycles of chemotherapy(7.5%) were dose-adjusted; 176 cycles of chemotherapy(10.7%) were delayed for median 5(3-13) days; 124 cycles(7.5%) required dose decrease. The overall relative dose intensity was >90%; the specific drug dose intensity was 93.6%(2620 mg×m⁻²×d⁻¹) for fluorouracil, 97.8%(83 mg×m⁻²×d⁻¹) for oxaliplatin, and 94.2%(155 mg×m⁻²×d⁻¹) for irinotecan. Twenty-three patients (7 of intestinal perforation, 7 of intestinal obstruction, 1 of grade 4 hematologic toxicity, and 8 of grade 3 fatigue) refused subsequent chemotherapy due to intolerable toxicity. Main grade 3 or 4 adverse events in patients were neutropenia in 69 cases (22.1%), fatigue in 35 cases (11.2%), and anemia in 28 cases (8.9%). Twenty serious adverse events (6.4%) occurred, including 13 patients of febrile neutropenia (4.2%), 7 patients of intestinal perforation (2.2%, 4 patients in upper rectum, 2 in sigmoid colon, and 1 in transverse colon cancer), and 9 of them had subsequent sepsis (2.9%). All the patients with intestinal perforation underwent emergency operation. No treatment-related deaths occurred. In 199 patients with metastatic CRC, because 22 patients did not receive image evaluation, the preliminary efficacy of 177 patients was actually evaluated. A total of 113 objective response events were observed. The overall response rate was 63.8%(113/177), partial response rate was 61.6%(109/177), clinically complete response rate was 2.3%(4/177), stable disease was 29.9% (53/177), progressive disease was 6.2%(11/177), and the disease control rate was 93.8%(166/177). In 127 patients receiving triplet drug, objective response rate was 40.9% for those with less than four cycles and 81.1% for those with more than four cycles (P<0.001).

CONCLUSIONThe mFOLFOXIRI regimen with reduced dose can be safely used in advanced CRC and has achieved promising results in terms of short-term efficacy.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Camptothecin ; administration & dosage ; analogs & derivatives ; Colorectal Neoplasms ; drug therapy ; Fluorouracil ; administration & dosage ; Humans ; Leucovorin ; administration & dosage ; Middle Aged ; Organoplatinum Compounds ; administration & dosage ; Retrospective Studies ; Treatment Outcome ; Young Adult

Rectal cancer is one of the most common malignancies in China. Total mesorectal excision (TME) plus neoadjuvant therapy is the standard treatment for locally advanced rectal cancer. After a development of over 20 years, neoadjuvant synchronous chemoradiotherapy has become the standard treatment and cornerstone of neoadjuvant therapy for rectal cancer. However, radiotherapy does not really increase the overall survival and is associated with long-term impact on the functions of anus, sex, urinary system and fertility, so the application of simple neoadjuvant chemotherapy rises gradually and becomes a potentially better treatment option. This paper elaborates the reason, present research status and future trend of the rising neoadjuvant chemotherapy.
Chemoradiotherapy ; China ; Humans ; Neoadjuvant Therapy ; Neoplasm Staging ; Rectal Neoplasms ; therapy ; Treatment Outcome

Objective To observe the relationship between Toll-like receptor 4 (TLR4) and the sensitivity of PANC1 cells to gemcitabine (GEM),and to analyze the potential mechanism.Methods PANC1 cells were divided into GEM group,lipopolysaccharide (LPS) + GEM group and TLR4-siRNA + GEM group.GEM group was treated by GEM alone.LPS + GEM group was pretreated with 1 mg/L LPS for 4 h and then treated by GEM.TLR4-siRNA + GEM group was transfected with 100 pmol/mL TLR4-siRNA for 4 h and then treated by GEM.The untreated cells were used as the control group.MTT method was used to detect the cell proliferation.Morphological changes and apoptosis rate of the cells were examined by Hoechst33258 staining and flow cytometry,respectively.The protein expression of TLR4,phosphorylated AKT (p-AKT) and activated Caspase-3 were detected by Western blot.Results The median inhibition concentration (ICs0) of GEM in the GEM group,LPS + GEM group and TLR4-siRNA + GEM group was (8.9 ± 0.32),(14.21 ±0.95),(3.96 ± 0.27) mg/L,respectively.The IC50 in LPS + GEM group was significantly higher than that in GEM group (P ＜ 0.01),and the IC50 of GEM in TLR4-siRNA + GEM group was significantly lower than that in GEM group (P ＜0.01).Compared with that in GEM group,the cells with typical apoptotic morphological changes were decreased in LPS + GEM group,which was increased in TLR4-siRNA + GEM group.The apoptotic rate in control group,GEM group,LPS + GEM group,TLR4-siRNA + GEM group was (2.1 ± 0.3) ％,(15.1 ± 2.3) ％,(9.8 ± 1.5) ％,(22.9 ± 3.1) ％,respectively.Compared with that in GEM group,the cells apoptotic rate was significantly reduced in LPS + GEM group (P ＜0.01),which was significantly increased in TLR4-siRNA + GEM group (P ＜0.01).TLR4 protein level in the 4 groups was 0.83 ±0.08,0.81 ±0.07,0.85 ±0.07 and 0.16 ±0.03;p-AKT protein level 0.61 ±0.05,0.36 ±0.03,0.73 ± 0.07 and 0.21 ± 0.02;activated Caspase-3 protein level was 0.66 ± 0.05,0.73 ± 0.07,0.45 ± 0.04 and 0.91 ± 0.07,respectively.The expression of TLR4 and p-AKT in TLR4-siRNA + GEM group was significantly lower than that in GEM group (P ＜0.01),while the expression of activated Caspase-3 protein was increased significantly (P ＜ 0.05).Compared with the GEM group,the expression of p-AKT protein in LPS + GEM group was significantly increased (P＜0.01),and the expression of activated Caspase-3 protein was significantly decreased (P＜0.01).Conclusions TLR4 can inhibit the sensitivity of pancreatic cancer PNAC1 cells to GEM,and the mechanism is related to the activation of PI3K/AKT pathway and downregulation of activated Caspase-3.