The production of high-quality oocytes requires precisely orchestrated intercellular communication. Extracellular vesicles (EVs) are cell-derived nanoparticles that play a vital role in the transfer of bioactive molecules, which has gained much attention in the field of diagnosis and treatment. Over the past ten years, the participation of EVs in the reproductive processes of oocytes has been broadly studied and has shown great potential for elucidating the intricacies of female reproductive health. This review provides an extensive discussion of the influence of EVs on oocytes, emphasizing their involvement in normal physiology and altered cargo under pathological conditions. In addition, the positive impact of therapeutic EVs on oocyte quality and their role in alleviating ovarian pathological conditions are summarized.
Humans ; Extracellular Vesicles/physiology* ; Oocytes/cytology* ; Female ; Animals ; Cell Communication/physiology*

Recent studies have identified a missense mutation in the β1-receptor (ADRB1-A187V) that exerts a pronounced impact on human sleep, with a noted decrease in protein abundance in vivo. The administration of β-blockers is frequently associated with sleep disturbances in clinical settings. In this study, we assessed the influence of various β-blockers on sleep within mouse models. Our findings indicated that β-blockers could induce varying degrees of arousal, sleep disruption, and a decrease in REMS (rapid eye movement sleep). We examined the dose-dependent effects of metoprolol and nebivolol on both sleep and cardiac functionality in both wild-type and Adrb1-A187V mutant mice. Our data suggested that, in contrast to cardiac effects, higher doses of metoprolol are required to have noted impact on sleep. No genotype effect was observed with metoprolol in terms of sleep or cardiac function. In contrast, the mutant mice demonstrated increased sensitivity to nebivolol, which exacerbated sleep fragmentation and impeded the onset of REMS. This study is expected to provide some reference for minimizing the occurrence of sleep disorders and reducing the adverse reactions of drugs to the greatest extent.

Objective:To investigate the effects of cerium oxide nanoenzyme-gelatin methacrylate anhydride (GelMA) hydrogel (hereinafter referred to as composite hydrogel) in the repair of infected full-thickness skin defect wounds in mice.Methods:This study was an experimental study. Cerium oxide nanoenzyme with a particle size of (116±9) nm was prepared by hydrothermal method, and GelMA hydrogel with porous network structure and good gelling performance was also prepared. The 25 μg/mL cerium oxide nanoenzyme which could significantly promote the proliferation of human skin fibroblasts and had high superoxide dismutase activity was screened out. It was added to GelMA hydrogel to prepare composite hydrogel. The percentage of cerium oxide nanoenzyme released from the composite hydrogel was calculated after immersing it in phosphate buffer solution (PBS) for 3 and 7 d. The red blood cell suspension of mice was divided into PBS group, Triton X-100 group, cerium oxide nanoenzyme group, GelMA hydrogel group, and composite hydrogel group, which were treated with corresponding solution. The hemolysis of red blood cells was detected by microplate reader after 1 h of treatment. The bacterial concentrations of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli were determined after being cultured with PBS, cerium oxide nanoenzyme, GelMA hydrogel, and composite hydrogel for 2 h. The sample size in all above experiments was 3. Twenty-four 8-week-old male BALB/c mice were taken, and a full-thickness skin defect wound was prepared in the symmetrical position on the back and infected with MRSA. The mice were divided into control group without any drug intervention, and cerium oxide nanoenzyme group, GelMA hydrogel group, and composite hydrogel group applied with corresponding solution, with 6 mice in each group. The wound healing was observed on 3, 7, and 14 d after injury, and the remaining wound areas on 3 and 7 d after injury were measured (the sample size was 5). The concentration of MRSA in the wound exudation of mice on 3 d after injury was measured (the sample size was 3), and the blood flow perfusion in the wound of mice on 5 d after injury was observed using a laser speckle flow imaging system (the sample size was 6). On 14 d after injury, the wound tissue of mice was collected for hematoxylin-eosin staining to observe the newly formed epithelium and for Masson staining to observe the collagen situation (the sample size was both 3). Results:After immersion for 3 and 7 d, the release percentages of cerium oxide nanoenzyme in the composite hydrogel were about 39% and 75%, respectively. After 1 h of treatment, compared with that in Triton X-100 group, the hemolysis of red blood cells in PBS group, GelMA hydrogel group, cerium oxide nanoenzyme group, and composite hydrogel group was significantly decreased ( P<0.05). Compared with that cultured with PBS, the concentrations of MRSA and Escherichia coli cultured with cerium oxide nanoenzyme, GelMA hydrogel, and composite hydrogel for 2 h were significantly decreased ( P<0.05). The wounds of mice in the four groups were gradually healed from 3 to 14 d after injury, and the wounds of mice in composite hydrogel group were all healed on 14 d after injury. On 3 and 7 d after injury, the remaining wound areas of mice in composite hydrogel group were (29±3) and (13±5) mm 2, respectively, which were significantly smaller than (56±12) and (46±10) mm 2 in control group and (51±7) and (38±8) mm 2 in cerium oxide nanoenzyme group (with P values all <0.05), but was similar to (41±5) and (24±9) mm 2 in GelMA hydrogel group (with P values both >0.05). On 3 d after injury, the concentration of MRSA on the wound of mice in composite hydrogel group was significantly lower than that in control group, cerium oxide nanoenzyme group, and GelMA hydrogel group, respectively (with P values all <0.05). On 5 d after injury, the volume of blood perfusion in the wound of mice in composite hydrogel group was significantly higher than that in control group, cerium oxide nanoenzyme group, and GelMA hydrogel group, respectively ( P<0.05). On 14 d after injury, the wound of mice in composite hydrogel group basically completed epithelization, and the epithelization was significantly better than that in the other three groups. Compared with that in the other three groups, the content of collagen in the wound of mice in composite hydrogel group was significantly increased, and the arrangement was also more orderly. Conclusions:The composite hydrogel has good biocompatibility and antibacterial effect in vivo and in vitro. It can continuously sustained release cerium oxide nanoenzyme, improve wound blood perfusion in the early stage, and promote wound re-epithelialization and collagen synthesis, therefore promoting the healing of infected full-thickness skin defect wounds in mice.

Objective:To analyze the molecular epidemiological characteristics of the Corona virus disease 2019 (COVID-19) cases in Shijiazhuang, which can reveal the origin of the outbreak and provide a scientific basis for COVID-19 prevention and control.Methods:From January 2 to January 8, 2021, a total of 404 samples from 170 COVID-19 cases were collected from the Shijiazhuang Fifth Hospital. The consensus sequence of 2019 novel Coronavirus(2019-nCoV) was obtained through multiplex polymerase chain reaction-based sequencing. The sequences of 170 COVID-19 cases were analyzed by the PANGOLIN, and the data were statistically analyzed by T-test.Results:Among the 404 COVID-19 samples, a total of 356 samples obtained high quality genome sequences (>95%,100×sequencing depth). The whole genome sequences of 170 COVID-19 cases were obtained by eliminating repeated samples. All 170 sequences were recognized as lineage B1.1 using PANGOLIN. The number of single nucleotide polymorphism arrange from 18-22 and most of the single nucleotide polymorphism were synonymous variants. All of 170 genomes could be classified into 48 sub-groups and most of the genomes were classified into 2 sub-groups (66 and 31, respectively).Conclusions:All cases in this study are likely originated from one imported case. The viruses have spread in the community for a long time and have mutated during the community transmission.

"Bio-separation engineering" is a compulsory course for undergraduate students majored in bioengineering, and an important part of the "emerging engineering education" system for bioengineering. Our teaching team follows the principle of "student development as the center, innovation thinking as the core". Guided by the concept of "learning achievement", we reconstructed the teaching contents of this course, and carried out the teaching reform aiming at solving several long-standing problems. These include, for instance, the theoretical teaching is separated from the experimental practice, and students cannot internalize the theoretical knowledge into practical ability in time. Moreover, the contents of course is out-of-date and out of line with industry demand, the teaching form and assessment methods are relatively single, and the students' professional ability and quality are not effectively cultivated. In the new curriculum system, in which the "online" and "offline" teaching are both applied, we broke the boundary between theoretical and experimental courses, and made the contents keep up with the forefront of industry development through research-based teaching. In terms of teaching methods and teaching evaluation, we made full use of modern information technology to enrich classroom teaching activities, and carried out complete, dynamic and diversified assessment for students. These teaching reform measures greatly improved the students' interest in learning this course, as well as their professionalism and research ability.
Bioengineering ; Biomedical Engineering ; Curriculum ; Humans ; Learning ; Students

Objective:To investigate the relationship between iodine nutrition level and thyroid disease.Methods:Totally 299 patients with thyroid disease who were treated at Shandong Provincial Institute for Endemic Disease Prevention and Control from 2016 to 2018 were selected as case group which was further divided into Graves' disease group (GD group, 137 patients), chronic lymphocytic thyroiditis group (HT group, 90 patients) and thyroid nodule group (72 patients). At the same time, 75 healthy people with no history of thyroid disease, normal thyroid color ultrasound and thyroid function were selected as control group. Morning urine was collected and urinary iodine was detected by arsenic cerium catalytic spectrophotometry. Fasting venous blood was extracted, and serum levels of thyroid stimulating hormone (TSH), free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid globulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) were detected by electrochemiluminescence method. Results:The difference of median urinary iodine in the 4 groups was statistically significant ( H = 42.530, P < 0.05). The medians urinary iodine in GD and HT groups (326.79, 341.91 μg/L) were higher than those of thyroid nodule group and control group (235.01, 187.32 μg/L, P < 0.05). The levels of TSH, FT 3 and FT 4 in GD group were compared with those of control group, and the differences were statistically significant ( P < 0.05). The positive rates of TgAb and TPOAb in HT group were significantly higher than those in GD, thyroid nodule and control groups, and the positive rates of TgAb and TPOAb in GD group were higher than those in thyroid nodule and control groups ( P < 0.05). Conclusions:GD and HT patients have excessive iodine nutrition, and high iodine intake may lead to the occurrence of these thyroid diseases (GD and HT). Thyroid function test combined with laboratory urinary iodine test can be used to diagnose thyroid diseases simply and quickly.

OBJECTIVE：To provide reference for the R&D of TCM patents for treating gastric cancer and layout. METHODS：TCM patents for treating gastric cancer collected by the State Intellectual Property Office and the European Patent Office Espacenet were retrieved from the inception to Dec. 31st， 2019. After the initial examination ，a second search was conducted based on the keywords such as “Stomachache”“Fuliang” “Accumulation”“Cancer of stomach ”“Gastric”and their synonyms. Each literature was read one by one and screened manually. Excel 2007 software was used to input general information of included patents. SPSS modeler 15.0 software and SPSS 22.0 software were used for association rule analysis and hierarchical cluster analysis of TCM used more than 30 times and top 30 frequently used. Based on patent analysis ，internal strength （S），weakness（W），external opportunity （O）and threat （T）of TCM for treating gastric cancer were analyzed ；based on this ，four different types of combination strategies were formulated. RESULTS & CONCLUSIONS ：Finally，385 patents were obtained ，including 379 domestic patents （98.44％） and 6 foreign patents （1.56％）. The number of patent applications and applicants of TCM for treating gastric cancer in China was on the rise during 1994-2016. The commonly used TCM for treating gastric cancer were mainly tonifying deficiency drugs and heat clearing drugs ， and the meridian tropism were mostly the stomach meridian and spleen meridian. According to the efficacy ，the commonly used drug combinations include the combination of tonifying spleen and Qi ，the combination of anti-cancer and detoxification ，and the combination of drying dampness and resolving phlegm. The results of hierarchical cluster analysis showed that Poria cocos ， Atractylodes macrocephala ，Astragalus membranaceus ，Scutellaria barbata ，Hedyotis diffusa and Glycyrrhiza uralensis were clustered into one category and the common combination for treating gastric cancer. The remaining cluster distributions are also in line with the characteristics of TCM syndrome differentiation and treatment. Strength of domestic TCM patents for treating gastric cancer were that the number of patents in China was taking a leading position in the world ，the patent system of key applicants was mature，the combination of compound patents embodied the characteristics of disease and dialectical theory. Weakness included low patent authorization rate ，to-be-improved effectiveness and safety studies of TCM patents ，weak development of TCM extract patents，low degree of patent internationalization and hanging same-family patents. Opportunities were that the demand for drugs for gastric cancer was increasing with each passing day ，and natione actively support the development of the TCM industry. Threats were that competitors in the international market had the potential to seize the market. The development of TCM for treating gastric cancer in China should take market demand and national policy support as an opportunity ，learn from TCM patent characteristic system of key applicants ，continue to give full play to the advantages of TCM in prevention and syndrome differentiation of disease，pay more efforts to the development of weak links such as TCM extracts ，safety and effectiveness ，improve the international competitiveness in the field of patents ，while establish a warning and navigation analysis system for patents to effectively reduce the intellectual property threats and risks of invention patents of China in the international environment.

Objective To summarize and analyze the epidemiological and clinical characteristics of patients with subacute thyroiditis (SAT),so as to provide a basis for prevention and treatment of the disease.Methods The epidemiological and clinical datas of 121 SAT patients,who were treated at the Shandong Provincial Institute for Endemic Disease Prevention and Control in 2015,were collected.The SAT patient's age,sex,lived in urban or rural areas,occupation and time of onset distributions were analyzed retrospectively.According to the clinical manifestations,the SAT patients were divided into types Ⅰ (mild/nodule type),Ⅱ (medium/normal),Ⅲ (severe/hyperthyroidism),and Ⅳ (delay),and clinical manifestations,auxiliary examination findings,treatment and outcome were summarized.Results Average age of the 121 cases of SAT patients was 41.36 years old,the youngest was 10 years old and the oldest was 76 years old.Most of the patients were 30-＜ 50 years old,which was accounted for 55.37％ (67/121).Most of the patients were female,which was accounted for 90.08％ (109/121).Most of the patients lived in rural areas,which was accounted for 59.50％ (72/121).Majority of the SAT patients were farmers,which was accounted for 43.80％ (53/121).Most onset of the disease was in November,accounted for 19.83％ (24/121),and the least was in June,accounted for 2.48％ (3/121),the peak of the incidence of SAT lied in autumn,and it was sporadic in the rest of the year.From the clinical classification,the mild type (61) and the medium type (46) were the largest part,a total of 107 cases,accounted for 88.43％ (107/121);while the severe type had 5 cases,accounted for 4.13％ (5/121);the delay type had 9 cases,accounted for 7.44％ (9/121).The clinical manifestations were as follows:anterior neck discomfort was 109 cases,accounted for 90.08％ (109/121);sore throat was 93 cases,accounted for 76.86％ (93/121).Auxiliary examination findings were as follows:thyroid iodine taken rate reduced in 121 cases,accounted for 100.00％ (121/121);thyroid nodule 96 cases,accounted for 79.34％ (96/ 121);total number of white blood cells increased in 52 cases,accounted for 42.98％ (52/121);neutrophil increased in 61 cases,accounted for 50.41％ (61/121);blood sedimentation significantly speed up in 49 cases,accounted for 40.50％ (49/121).All of the 121 patients were cured.Conclusions Majority of the patients are female,young aduhs and farmers.The peak of the incidence of SAT lies in autumn.The proportion of mild,medium type is the highest,we suggest this disease should be early diagnosis and treatment.

Objective To evaluate the feasibility of T2 *mapping T2 *value combined with DWI ADC value in quantitative assessment of the activity of sacroiliitis.Methods 30 patients diagnosed with ankylosing spondylitis (AS)were divided into 2 groups as acute group (n=17)and chronic group (n=13)according to the BASDAI scores of the clinical severity of disease.And 20 healthy adults were recruited as control group.All groups were examined by MR with traditional sequence,T2 *mapping and DWI in the sacroiliac joint.The T2 *value and ADC value of the bone marrow edema region and normal region were measured.Furthermore,the imaging data and the clinical scores were statistical analysis and compared among three groups.Results T2 *values and ADC values in acute group of AS patients were higher than chronic group (P<0.05),as well as compared with healthy volunteers (P<0.05).There was no statistically significant difference between the chronic group of AS patients and control group (P>0.05).Positive correlation between ADC value and BASDAI was observed in patients group.Conclusion T2 *mapping combined with DWI imaging in AS is beneficial for early diagnosis and quantitative analysis of the activity of sacroiliitis.