Female ; Humans ; Endodermal Sinus Tumor/pathology* ; Adenocarcinoma/pathology* ; Choriocarcinoma/pathology*

Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer(CRC).Cisplatin(DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeutic drug effects which are characterized by the activation of slow-cycle programs and DNA repair.Among the elements that lead to DDP resistance,O6-methylguanine(O6-MG)-DNA-meth-yltransferase(MGMT),a DNA-repair enzyme,performs a quintessential role.In this study,we clarify the significant involvement of MGMT in conferring DDP resistance in CRC,elucidating the underlying mechanism of the regulatory actions of MGMT.A notable upregulation of MGMT in DDP-resistant cancer cells was found in our study,and MGMT repression amplifies the sensitivity of these cells to DDP treatment in vitro and in vivo.Conversely,in cancer cells,MGMT overexpression abolishes their sensi-tivity to DDP treatment.Mechanistically,the interaction between MGMT and cyclin dependent kinase 1(CDK1)inducing slow-cycling cells is attainted via the promotion of ubiquitination degradation of CDK1.Meanwhile,to achieve nonhomologous end joining,MGMT interacts with XRCC6 to resist chemotherapy drugs.Our transcriptome data from samples of 88 patients with CRC suggest that MGMT expression is co-related with the Wnt signaling pathway activation,and several Wnt inhibitors can repress drug-resistant cells.In summary,our results point out that MGMT is a potential therapeutic target and predictive marker of chemoresistance in CRC.

Objective    To compare the in-hospital outcomes of transapical transcatheter aortic valve replacement (TA-TAVR) for bicuspid aortic valve (BAV) patients and tricuspid aortic valve (TAV) patients. Methods    Patients (including BAV and TAV patients) who underwent TA-TAVR with the J-ValveTM in West China Hospital from July 2014 to July 2020 were included consecutively. The clinical outcomes of the patients were analyzed. Results    A total of 354 patients were included in the study, 75 in the BAV group and 279 in the TAV group. There were 229 males and 125 females with a mean age of 72.2±6.0 years. No death occurred during the procedure, and the overall technical success rate was 97.7%. The all-cause in-hospital mortality rate was 1.4%. Twenty (26.7%) patients with BAV and 46 (16.5%) patients with TAV had mild or higher perivalvular leaks immediately after the procedure. No patients with BAV required permanent pacemaker implantation postoperatively, while 13 (4.7%) TAV patients required permanent pacemaker implantation, with an overall pacemaker implantation rate of 3.7%. One (1.3%) BAV patient and 7 (2.5%) TAV patients developed acute kidney injury postoperatively. One (1.3%) BAV patient and 1 (0.4%) TAV patient developed peri-operative myocardial infarction. The average postoperative hospital stay was 7.6±3.6 d for BAV patients and 8.6±6.1 d for TAV patients. There was no statistical difference in primary or secondary in-hospital outcomes between BAV and TAV patients (P>0.05). Conclusion    Compared to TAV patients, BAV patients have similar in-hospital outcomes, with a low incidence of adverse clinical outcomes, which provides preliminary evidence for its implementation in Chinese patients with a high proportion of BAV.

OBJECTIVE: Identifying novel strategies to prevent particulate matter (PM)-induced lung injury is crucial for the reduction of the morbidity of chronic respiratory diseases. The combined intervention represented by herbal formulae for simultaneously targeting multiple pathological processes can provide a more beneficial effect than the single intervention. The aim of this paper is therefore to design a safe and effective medicinal and edible Chinese herbs (MECHs) formula against PM-induced lung injury. METHODS: PM-induced oxidative stress, inflammatory response and apoptosis A549 cell model were used to screen anti-oxidant, anti-inflammatory and anti-apoptotic MECHs, respectively. A network pharmacology method was utilized to rationally design a novel herbal formula. Ultra performance liquid chromatography-mass spectrometer was utilized to assess the quality control of MECHs formula. The excretion of magnetic iron oxide nanospheres of the MECHs formula was estimated in zebrafish. The MECH formula against PM-induced lung injury was investigated with mice experiments. RESULTS: Five selected herbs were rationally designed to form a new MECH formula, including Citri Exocarpium Rubrum (Juhong), Lablab Semen Album (Baibiandou), Atractylodis Macrocephalae Rhizoma (Baizhu), Mori Folium (Sangye) and Polygonati Odorati Rhizoma (Yuzhu). The formula effectively promoted the magnetic iron oxide nanospheres excretion in zebrafish. The mid/high dose formula significantly prevented PM-induced lung damage in mice by enhancing the activity of SOD and GSH-Px, reducing the MDA and ROS level and attenuating the upregulation of pro-inflammatory cytokine (IL-6, IL-8, IL-1β and TNF-α), down regulating the protein expression of NF-κB, STAT3 and Caspase-3. CONCLUSION Our findings suggest that the effective MECHs formula will become a novel strategy for preventing PM-induced lung injury and provide a paradigm for the development of functional foods using MECHs.

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.

OBJECTIVE: To establish a snail control approach for spraying chemicals with drones against Oncomelania hupensis in complex snail habitats in hilly regions, and to evaluate its molluscicidal effect. METHODS: The protocol for evaluating the activity of spraying chemical molluscicides with drones against O. hupensis snails was formulated based on expert consultation and literature review. In August 2022, a pretest was conducted in a hillside field environment (12 000 m²) north of Dafengji Village, Dacang Township, Weishan County, Yunnan Province, which was assigned into four groups, of no less than 3 000 m² in each group. In Group A, environmental cleaning was not conducted and 5% niclosamide ethanolamine salt granules were sprayed with drones at a dose of 40 g/m², and in Group B, environmental cleaning was performed, followed by 5% niclosamide ethanolamine salt granules sprayed with drones at a dose of 40 g/m², while in Group C, environmental cleaning was not conducted and 5% niclosamide ethanolamine salt granules were sprayed with knapsack sprayers at a dose of 40 g/m², and in Group D, environmental cleaning was performed, followed by 5% niclosamide ethanolamine salt granules sprayed with knapsack sprayers at a dose of 40 g/m². Then, each group was equally divided into six sections according to land area, with Section 1 for baseline surveys and sections 2 to 6 for snail surveys after chemical treatment. Snail surveys were conducted prior to chemical treatment and 1, 3, 5, 7 days post-treatment, and the mortality and corrected mortality of snails, density of living snails and costs of molluscicidal treatment were calculated in each group. RESULTS: The mortality and corrected mortality of snails were 69.49%, 69.09%, 53.57% and 83.48%, and 68.58%, 68.17%, 52.19% and 82.99% in groups A, B, C and D 14 days post-treatment, and the density of living snails reduced by 58.40%, 63.94%, 68.91% and 83.25% 14 days post-treatment relative to pre-treatment in four groups, respectively. The median concentrations of chemical molluscicides were 37.08, 35.42, 42.50 g/m² and 56.25 g/m² in groups A, B, C and D, and the gross costs of chemical treatment were 0.93, 1.50, 0.46 Yuan per m² and 1.03 Yuan per m² in groups A, B, C and D, respectively. CONCLUSIONS The molluscicidal effect of spraying 5% niclosamide ethanolamine salt granules with drones against O. hupensis snails is superior to manual chemical treatment without environmental cleaning, and chemical treatment with drones and manual chemical treatment show comparable molluscicidal effects following environmental cleaning in hilly regions. The cost of chemical treatment with drones is slightly higher than manual chemical treatment regardless of environmental cleaning. Spraying 5% niclosamide ethanolamine salt granules with drones is recommended in complex settings with difficulty in environmental cleaning to improve the molluscicidal activity and efficiency against O. hupensis snails.
Niclosamide/pharmacology* ; Ethanolamine/pharmacology* ; Unmanned Aerial Devices ; China ; Molluscacides/pharmacology* ; Ethanolamines

Objective:To provide strategical reference for large-scale colorectal cancer screening with full regional coverage by analyzing the results of the first colorectal cancer screening in the target population in Linhai city,Zhejiang Province. Methods:The target population of 50-74 years old in Linhai were invited to take part in the colorectal cancer screening program from 2020 to 2021.The risk of colorectal cancer of the participants were preliminarily evaluated by questionnaire and qualitative fecal occult blood test(FOBT),and participants with positive screening results were suggested to take colonoscopy test for further evaluation.The screening results were collected and analyzed. Results:A total of 71 942 people were screened from 2020 to 2021,and 15 1 70 of them were found positive in preliminary screening.The positive rate in males was significantly higher than that in females(x 2=724.005,P＜0.001),and the positive rate was highest in the population of 60-69 years old during preliminary screening.The compliance rate of colonoscopy was 24.1 9％with no significant difference between males and females(x 2=0.256,P=0.61 3),showing a decreasing trend as the age increases.From 2020 to 2021,the detection rate of lesions by colonoscopy was 52.92％,with 47 case of colorectal cancer(CRC),333 case of advanced colorectal adenoma,561 case of non-advanced colorectal adenoma and 1 001 case of benign lesions.The detection rate of lesions in males was much higher than that in females(x 2=82.451,P＜0.001).The detection rates of lesions,advanced colorectal adenoma,and non-advanced adenoma showed increasing trends with the age.The compliance rate of colonoscopy,the detection rate of lesions,and the detection rate of CRC,advanced colorectal adenoma,and non-advanced adenoma were 32.94％,69.53％,2.87％,1 6.85％and 1 9.71％,respectively,in participants who were both assessed as high-risk according to questionnaire evaluation and FOBT positive,the highest among all participants.The compliance rate of colonoscopy in 2021 was obviously higher than that in 2020(32.11％vs 1 9.09％,P＜0.001),but no significant difference was found in the detection rate of lesions between 2021 and 2020(P＞0.05). Conclusion:From 2020 to 2021,the compliance rate of colonoscopy was low and the detection rate of colorectal lesions was high during the screening of colorectal cancer in the target population in Linhai,Zhejiang Province.It is necessary to enhance the public awareness of the importance of colorectal cancer screening,standardize the enrollment criteria,and improve the compliance of colonoscopy,in orderto give full play to primary screening in the general public.

Objective: To investigate the clinicopathological characteristics of esophageal carcinoma with gland duct differentiation. Methods: The clinical, morphologic and immunohistochemical (IHC) features of eight cases of esophageal carcinoma with gland duct differentiation diagnosed from 2012 to 2022 at the First Affiliated Hospital of Soochow University were summarized. Results: There were four males and four females, with a mean age of 68.5 (range 59-82) years. Two tumors were located in middle esophagus, five in the lower esophagus, and one in the cardia. The mean diameter was 2.4 cm (range 0.6-4.5 cm). The tumor had a bilayer epithelial structure, including the inner luminal epithelium and the outer basal epithelium. Immunohistochemistry showed that CK7 (8/8) and CK18 (8/8) were positive in the inner epithelium. p40 (8/8), p63 (8/8) and CK5/6 (8/8) were positive in the outer epithelium. SMA, calponin and CD117 were all negative. p53 mutants were found in all eight cases (strong and diffuse positivity in 6/8; complete loss of expression in 2/8). No columnar metaplasia, intestinal metaplasia and ectopic gastric mucosa were observed in the surface squamous epithelium in the cases. The mean follow-up time was 21.5 months (range 5-51 months). Seven patients survived and one patient died 31 months after surgery due to recurrence and liver metastasis. Conclusion: Esophageal carcinoma with esophageal gland duct differentiation is a rare tumor with unique histologic and IHC characteristics.
Male ; Female ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Esophageal Neoplasms/pathology* ; Epithelium/pathology* ; Metaplasia/metabolism* ; Carcinoma/pathology*

Humans ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections/complications* ; Cholangiocarcinoma/pathology* ; Carcinoma, Squamous Cell ; Bile Ducts, Intrahepatic/pathology* ; Bile Duct Neoplasms/pathology*

Humans ; Thyroid Cancer, Papillary ; Neck/pathology* ; Lymph Nodes/pathology* ; Thyroid Neoplasms/pathology* ; Lymphoma, T-Cell/pathology*