Objective: To investigate the effect of neurite outgrowth inhibitor extracellular peptide residues 1-40 (NEP1-40) combined with poly (lactic-co-glycolic acid) (PLGA) and gelatin electrospun fiber membrane on facial nerve repair in rats. Methods: According to the principle of random grouping, 108 male SD rats were divided into four groups (n = 27 in each group, approved by the ethics committee), namely, the sham group, control group, PLGA group, and NEP1-40 + PLGA group. A facial nerve fracture model was established for all of the groups except for the sham group. The control group received no further treatment, the PLGA group and the NEP1-40+PLGA group were supported by PLGA membrane, and the NEP1-40+PLGA group received one immediate local injection of NEP1-40 (5 μg/μL) at a dose of 10 μL. Facial nerve function analysis, electrophysiological examination, transmission electron microscope observation, HE staining, and immunohistochemical staining of myelin marker S100β and axonal marker β3-tubulin were used to evaluate the recovery of injured facial nerves of rats at 2, 4 and 8 weeks. Results : At 8 weeks, the facial nerve function score of the NEP1-40+PLGA group was better than that of the control group and PLGA group (P < 0.001), and facial nerve function was significantly restored. Electrophysiological examination of nerve action potentials at the injured facial nerve showed that the amplitude in the NEP1-40+PLGA group was higher than that of the control group and PLGA group (P < 0.001), but there was no significant difference in latency and conduction velocity results between the groups (P > 0.05). At 2, 4, and 8 weeks, transmission electron microscopy showed that the number of myelinated nerve fibers and myelin sheath thickness in the cross-section of the injured facial nerve in the NEP1-40+PLGA group were greater than those in the other groups (P < 0.05). At 8 weeks, HE staining showed that the facial nerves in the control group had partially recovered, but the overall cell distribution was uneven and the boundary with surrounding tissues was slightly blurred. In contrast, the NEP1-40+PLGA group had a relatively uniform cell distribution and a clearer boundary with surrounding tissues. At 2, 4, and 8 weeks, the immunohistochemical results showed that in the cross-section of the injuried facial nerve, NEP1-40 increased the expression of neural markers S100 β and β3-tubulin, especially β3-tubulin, which was close to normal levels (P > 0.05) Conclusion NEP1-40 is beneficial for the generation of new myelin sheaths and axons at the site of injury, and it can promote the repair and regeneration of injured facial nerves to a certain extent, thus accelerating the recovery of injured nerve function.

ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus， in order to obtain the optimal fermentation conditions and flora structure， and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2（ITS2） high-throughput sequencing， combined with fungal community diversity analysis and fungal community structure analysis， were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7， 14， 21 d（numbered Y1-Y3 for the former， and numbered F1-F3 for the latter）， respectively. At the same time， the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， combined with principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and compound retention time， parent ions， characteristic fragment ions and other information， the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method， while in the non-pressure-shelf natural fermentation method， there was a significant difference with the fermentation process， and at the genus level， the dominant genus of samples Y1， Y2， Y3 and F2 was Aspergillus， while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable， and the microbial community structure was more stable， which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis， including 70 flavonoids， 38 coumarins， 10 alkaloids， 34 organic acids and 3 other compounds. After fermentation， two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition， multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods， mainly including flavonoids， organic acids and coumarins. Comprehensively， the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable， the species richness was high and the overall content of differential compounds was high， which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation， the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds， and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus， as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.

ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus， in order to obtain the optimal fermentation conditions and flora structure， and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2（ITS2） high-throughput sequencing， combined with fungal community diversity analysis and fungal community structure analysis， were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7， 14， 21 d（numbered Y1-Y3 for the former， and numbered F1-F3 for the latter）， respectively. At the same time， the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， combined with principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and compound retention time， parent ions， characteristic fragment ions and other information， the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method， while in the non-pressure-shelf natural fermentation method， there was a significant difference with the fermentation process， and at the genus level， the dominant genus of samples Y1， Y2， Y3 and F2 was Aspergillus， while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable， and the microbial community structure was more stable， which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis， including 70 flavonoids， 38 coumarins， 10 alkaloids， 34 organic acids and 3 other compounds. After fermentation， two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition， multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods， mainly including flavonoids， organic acids and coumarins. Comprehensively， the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable， the species richness was high and the overall content of differential compounds was high， which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation， the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds， and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus， as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.

ObjectiveTo observe ovarian microvascular damage in rats with cold coagulation and blood stasis syndrome and to explore the mechanism by which Liangfang Wenjing decoction improves this condition in rats. MethodsFifty SPF female SD rats were randomly divided into a blank group， a model group， low-dose （8.1 g·kg^-1） and high-dose groups （16.2 g·kg^-1） of Liangfang Wenjing decoction， and a 4-phenylbutyric acid （0.1 g·kg^-1） group， with 10 rats in each group. The ice-water bath method was employed to establish the rat model of cold coagulation and blood stasis syndrome. Concurrent with modeling， Liangfang Wenjing decoction was administered continuously for 21 days， once daily. The rats' syndrome manifestations and estrous cycles were recorded. The enzyme-linked immunosorbent assay （ELISA） was used to detect serum reproductive hormone levels and levels of endothelin-1 （ET-1）， nitric oxide （NO）， thrombomodulin （TM）， and von Willebrand factor （vWF） in ovarian tissue. Prothrombin time （PT）， activated partial thromboplastin time （APTT）， thrombin time （TT）， and fibrinogen （FIB） were measured. The ovarian microcirculatory blood perfusion was detected by laser speckle contrast imaging. Hematoxylin-eosin （HE） staining was performed to observe the ovarian histopathology， flow cytometry to detect ovarian apoptosis rate， and transmission electron microscopy to observe the ultrastructure of ovarian microvascular endothelial cells. Western blot was employed to detect the protein expression of endothelial nitric oxide synthase （eNOS）， phosphorylated eNOS （p-eNOS）， Caspase-3， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， glucose-regulated protein 78 （GRP78）， C/EBP homologous protein （CHOP）， inositol-requiring enzyme1α （IRE1α）， p-IRE1α， apoptosis signal-regulating kinase 1 （ASK1）， p-ASK1， c-Jun N-terminal kinase （JNK）， and p-JNK. Immunofluorescence was used to detect ovarian Bax and Bcl-2 expression in microvascular endothelial cells. ResultsCompared with the blank group， the model group showed signs of cold coagulation and blood stasis syndrome， prolonged estrus cycles， and reproductive hormone disorders. Histopathological results revealed a decrease in follicle counts at all stages and disorganized granulosa cell arrangement. Ovarian microcirculatory perfusion was significantly decreased （P<0.01）. PT， APTT， and TT were reduced （P<0.05， P<0.01）， while FIB levels were increased （P<0.05）. In ovarian tissue， NO content was decreased， while ET-1， vWF， and TM levels were increased significantly （P<0.01）. The apoptosis rate of ovarian cells was markedly increased （P<0.01）. Furthermore， p-eNOS/eNOS and Bcl-2 were decreased （P<0.05）， whereas Bax， cleaved-Caspase-3/Caspase-3， GRP78， CHOP， p-IRE1α/IRE1α， p-ASK1/ASK1， and p-JNK/JNK expression showed significant increases （P<0.05， P<0.01）. Compared with the model group， Liangfang Wenjing decoction intervention alleviated the symptoms of cold coagulation and blood stasis， gradually restored the estrus cycle， and improved ovarian histopathology and endothelial cell ultrastructure. Microcirculatory blood perfusion was significantly elevated （P<0.05）. NO content in ovarian tissue was elevated， while ET-1， vWF， and TM levels were significantly decreased （P<0.05， P<0.01）. The p-eNOS/eNOS ratio and Bcl-2 expression were significantly elevated （P<0.05）， while the expression of Bax， cleaved-Caspase-3/Caspase-3， GRP78， CHOP， p-IRE1α/IRE1α， p-ASK1/ASK1， and p-JNK/JNK was significantly decreased （P<0.05， P<0.01）. ConclusionLiangfang Wenjing decoction may regulate the IRE1α/ASK1/JNK signaling pathway to inhibit endoplasmic reticulum stress， attenuate apoptosis， and improve microvascular endothelial injury in ovaries of rats with cold coagulation and blood stasis syndrome.

Objective:To explore the feasibility of applying BOPPPS (B-bridge in, O-objective, P-pre-assessment, P-participatory learning, P-post-assessment, S-summary) course design mode in the teaching of internal medicine practice for nursing undergraduates.Methods:A total of 73 nursing interns of Kunming Medical University were selected as subjects and divided into the experimental group ( n=30) and the control group ( n=43). The experimental group adopted the practice teaching method based on BOPPPS model, while the control group adopted the traditional teaching method. Students' evaluation was collected by questionnaire. The students' comprehensive reasoning ability, holistic nursing skills ability and clinical nursing evaluation ability were evaluated by taking out questions from the question bank. And the results of teachers' evaluation on the participation of case study and problem solving in the process of students' internship were collected. SPSS 20.0 was used for t-test. Results:The students' evaluation of the practice process in the experimental group (86.81±2.85) was significantly better than that in the control group (82.61±3.82) ( P<0.001). The experimental group was significantly better than the control group in comprehensive reasoning of clinical thinking and assessment of holistic nursing ability ( P <0.001). Teachers' evaluation in the experimental group was better than that in the control group ( P <0.05). The overall effect of the experimental group (20.60±1.73) was significantly better than that of the control group (17.84±1.70) ( P <0.001). Conclusion:BOPPPS mode is helpful for teachers to carry out and demonstrate holistic nursing teaching with symptoms as the core according to the overall teaching objectives of nursing internal medicine, optimize the time arrangement and knowledge structure, improve the practice efficiency, and promote the establishment of holistic nursing thinking mode of students.

【Objective】 To investigate the practice and benefit of national standardized management of type 2 diabetes in Yulin City. 【Methods】 We recruited the adult type 2 diabetes patients who sought medical help at our hospital from May 2020 to October 2022 as subjects. We collected their basic information (sex and age); measured height, weight, waist and hip circumference, and blood pressure; calculated body mass index (BMI); and detected blood glucose, c-peptide, HbA1c, biomarkers, urinary microalbumin, sensory nerve conduction velocity of lower limbs, ABI, and subcutaneous and visceral fat at the time of MMC recruited and the end of six months. T test and Mann-Whitney U rank sum test were used for measurement data and χ² test or Fisher’s exact probability method for counting data to analyze the data. 【Results】 After 6 months, the levels of fasting blood glucose, postprandial blood glucose, HbA1c, and visceral and subcutaneous fat in all the patients decreased, but the level of fasting c-peptide increased compared with the baseline (all P<0.05). Secondly, compared with the baseline, the control rate of HbA1c (35.21% vs. 13.71% ) and the comprehensive control rate (13.97% vs. 7.26% ) were both significantly increased at six months (P<0.05). Thirdly, after 6 months, the levels of fasting blood glucose, postprandial blood glucose, HbA1c, TG, TC, and UA were decreased more, while the fasting c-peptide and postprandial c-peptide were increased more in the patients of the HbA1c standard group (HbA1c<7% ) than those of the non-standard group. 【Conclusion】 The multiple benefits of blood glucose, blood lipid, uric acid and islet function can be achieved by taking type 2 diabetes patients into MMC. Meanwhile, the rates of HbA1c control and comprehensively reaching the standard are significantly increased. Therefore, MMC can explore a new way for the management of type 2 diabetic patients in this area.

Fusobacterium nucleatum (F. nucleatum) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this study, we built an F. nucleatum infectious model with human periodontal ligament stem cells (PDLSCs) and showed that F. nucleatum could inhibit proliferation, and facilitate apoptosis, ferroptosis, and inflammatory cytokine production in a dose-dependent manner. The F. nucleatum adhesin FadA acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β, IL-6 and IL-8. Further study showed that FadA could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F. nucleatum infection. NFκB1 and NFκB2 upregulated after 3 h of F. nucleatum-infection, and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects of F. nucleatum-infection. Collectively, this study unveils the potential pathogenic mechanisms of F. nucleatum and the host inflammatory response at the early stage of F. nucleatum infection.
Humans ; Fusobacterium nucleatum/metabolism* ; NF-kappa B/metabolism* ; Periodontal Ligament/metabolism* ; Signal Transduction ; Fusobacterium Infections/pathology* ; Stem Cells/metabolism*

Objective:To explore the effect of positive psychological group training in epilepsy patients.Methods:From January to December 2020, a total of 60 epilepsy patients in Department of Neurology in Shandong Daizhuang Hospital were selected as the research objects using the convenience sampling method, and were randomly divided into the observation group and the control group by random number table, with 30 cases each. The control group received routine nursing, and the observation group received positive psychological group training on the basis of the control group, lasting for 8 weeks. The scores of Self-Esteem Scale, the Feelings of Inadequacy Scale, Shame Scale and General Perceived Self-Efficacy Scale were compared between the two groups.Results:After intervention, the behavioral shame and body shame scores of the observation group were lower than those of the control group, and the differences were statistically significant ( P<0.01). After intervention, the scores of Self-Esteem Scale, the Feelings of Inadequacy Scale and General Perceived Self-Efficacy Scale of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.01) . Conclusions:Positive psychological group training can improve epilepsy patients' inferiority, self-esteem and self-efficacy, reduce sense of shame, which is worthy of clinical application.

The cold congeal and blood stasis syndrome is a common clinical traditional Chinese medicine（TCM） syndrome. The animal model of cold ongeal and blood stasis syndrome is the basis for exploring the essence of TCM cold congeal and blood stasis syndrome，and the premise of follow-up TCM clinical research.This paper summarized the preparation method， theoretical support，and evaluation method of animal models of cold congeal and blood stasis syndrome in recent years and analysed the strengthens and weaknesses of different models. At present，the common animal models of cold congeal and blood stasis syndrome mainly include etiological model，etiological and pathological composite model and disease-syndrome combination model. The etiological model was mainly prepared by cold exposure，which could be divided into whole-body freezing， ice bath and local frostbite. The etiological and pathological composite model was mainly prepared by cold stimulation combined with epinephrine injection. The common disease-syndrome combination models included the coronary heart disease model of cold congeal and blood stasis syndrome，primary dysmenorrhea model of cold congeal and blood stasis syndrome，endometriosis model of cold congeal and blood stasis syndrome， and arteriosclerosis obliterans model of cold congeal and blood stasis syndrome. The three models have both advantages and disadvantages. Specifically， the disease-syndrome combination model had the highest consistency with clinical practice and was more reliable and practical. However， the disease types of this model were specific，and the combination method of disease and syndrome was controversial. The evaluation indicators of the animal models of cold congeal and blood stasis syndrome focused on the characterization of the syndrome and the physico-chemical indicators related to blood flow，such as blood rheology，coagulation function and microcirculation. In addition， some scholars explored the evaluation indicators from the aspects of vasomotor function，endocrine and energy metabolism. The objectivity and specificity of the current model evaluation methods needed to be further improved. The research of animal model of cold congeal and blood stasis syndrome should be based on clinical practice and oriented by clinical demand. Only by establishing animal models that are highly consistent with the characteristics of clinical disease and syndrome can we better reveal the essence of cold congeal and blood stasis syndrome and promote the modernization of TCM.

Objective:To explore the clinical experience in care for deep neck infection (DNI) and to analyze the factors influencing surgical treatment outcome.Methods:A retrospective analysis was conducted on 61 patients with DNI admitted to the Department of Otorhinolaryngology Head and Neck Surgery of Yantai Yuhuangding Hospital from March 2013 to April 2019, including 33 males and 28 females, aged from 6 months to 81 years with a median age of 49 years. Patients were divided into two groups, 31 cases with localized infection (neck abscess) in Group A and 30 cases with diffuse infection (neck necrotizing fasciitis) in Group B. Patients in two groups were compared for sex, age, hospital stay, diabetes, tracheostomy, drainage methods, mediastinal infection, and pathogenic bacteria. The influence of different drainage methods on hospital stay in Group A was analyzed. SPSS 25.0 software was used for statistical analysis.Results:Of the 61 patients, 45 patients underwent surgical incision and drainage (21 cases in Group A and 24 cases in Group B), 23 patients underwent ultrasound-guided fine needle aspiration (UG-FNA) and catheter drainage (10 cases in Group A and 13 cases in Group B), and 7 patients in Group B were treated with both drainage methods. Pathogens were cultured in 31 cases (50.82%). There were significant differences in hospital stay, drainage method and mediastinal infection (χ 2 values were 26.890, 8.687 and 6.035, respectively, P<0.05), but no significant difference was found in sex, age, diabetes, tracheotomy and pathogenic bacteria (χ 2 values were 0.157, 3.685, 2.434, 3.631 and 0.807, respectively, P>0.05) between the two groups. There was no significant difference in hospital stay between two drainage methods in patients in Group A (χ 2=1.560, P>0.05). Conclusions:There were significant differences in hospital stay, drainage method and mediastinal infection between patients with localized infection and diffuse infection, as diffuse infection is often associated with serious complications. UG-FNA and catheter drainage is an optional method for the treatment of localized infection, with minimal invasion and no influence on hospital stay.