Objective:To preliminarily explore therapeutic effects and possible molecular mechanisms of sinomenine on atopic dermatitis (AD) -like mouse models.Methods:Thirty female BALB/c mice (6 - 8 weeks old) were randomly divided into 5 groups: blank control group, model group, positive control group, topical sinomenine group, and oral sinomenine group. Except for the blank control group, all groups were subjected to repeated topical stimulation with 2,4-dinitrochlorobenzene (DNCB) on the dorsal skin to establish an AD-like mouse model. After modeling, no special treatment was given to the blank control group, the positive control group was topically treated with 100 μg of 0.1% mometasone furoate cream twice daily on the lesions, the topical sinomenine group was topically treated with 100 μl of 10 mg/ml sinomenine solution twice daily on the lesions, and the oral sinomenine group was gavaged with sinomenine solution at a dose of 100 mg·kg -1·d -1 (100 μl per dose, twice daily) . Treatments lasted for 14 days. Twelve hours after the final treatment, the severity of skin lesions in each group was assessed. Blood samples were collected via enucleation, and serum levels of interleukin (IL) -1β, IL-6, and immunoglobulin E (IgE) were measured using enzyme-linked immunosorbent assay (ELISA) . Histopathological changes in dorsal skin lesions were observed, and immunohistochemical study was performed to detect the expression levels of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF) -κB p65 in skin tissues, expressed as the percentage of the immunopositive area. One-way analysis of variance was used for multiple group comparisons, while Tukey′s test or the Games-Howell test was applied for post-hoc comparisons between groups. Results:Compared with the blank control group, the model group exhibited epidermal hyperkeratosis with parakeratosis, thickening of the spinous layer, spongiosis, significant inflammatory cell infiltration, and prominent angiogenesis. In contrast, the positive control group, topical sinomenine group, and oral sinomenine group showed reduced spinous layer thicknesses, decreased inflammatory cell infiltration, and less pronounced angiogenesis compared to the model group. In the blank control group, model group, positive control group, topical sinomenine group, and oral sinomenine group, the severity scores of skin lesions were 0, 8.83 ± 0.75, 4.33 ± 1.08, 2.58 ± 0.49, 2.83 ± 0.93 respectively, the serum levels of IL-1β were 52.58 ± 1.72, 168.40 ± 7.23, 57.07 ± 6.39, 85.74 ± 4.15, 100.30 ± 11.55 pg/ml respectively, IL-6 levels were 86.88 ± 4.60, 215.00 ± 5.02, 79.34 ± 4.91, 127.20 ± 1.06, 149.00 ± 6.21 pg/ml respectively, IgE levels were 2 159.00 ± 176.00, 3 493.00 ± 89.61, 2 294.00 ± 158.10, 2 550.00 ± 214.70, 2 814.00 ± 119.70 μg/ml respectively, the expression levels of p38 MAPK in skin tissues were 3.03% ± 3.38%, 12.95% ± 6.89%, 2.14% ± 1.28%, 5.28% ± 3.71%, 3.85% ± 2.26% respectively, and NF-κB p65 expression levels were 0.61% ± 0.49%, 18.92% ± 6.96%, 3.77% ± 1.90%, 5.66% ± 2.28%, 6.25% ± 3.14% respectively; the differences in all the above parameters were statistically significant among groups (all P < 0.05) . Compared with the blank control group, the model group had significantly increased skin lesion severity scores, serum IL-1β, IL-6, and IgE levels, as well as elevated expression of p38 MAPK and NF-κB p65 in skin tissues (all P < 0.01) . Compared with the model group, the positive control group, topical sinomenine group, and oral sinomenine group showed significantly reduced skin lesion severity scores, decreased serum IL-1β, IL-6, and IgE levels, and lower expression of p38 MAPK and NF-κB p65 in skin tissues (all P < 0.05) . Compared with the positive control group, the topical and oral sinomenine groups exhibited further reductions in skin lesion severity scores (both P < 0.05) . Additionally, the topical sinomenine group showed significantly lower serum levels of IL-1β and IL-6 compared with the oral sinomenine group (both P < 0.05) . Conclusion:Sinomenine solution could obviously alleviate the severity of skin lesions in AD-like mouse models, likely by down-regulating the expression of IL-1β, IL-6 and IgE, inhibiting the MAPK/NF-κB signaling pathway, and thus reducing the degree of inflammation.

Objective:To construct a teaching model for Geriatric Nursing based on metacognitive strategy and to test its effectiveness in teaching undergraduate nursing students.Methods:A quasi-experimental research design was adopted. The intervention group consisted of 49 undergraduate nursing students enrolled in 2019 at Sun Yat-sen University, while the control group was made up of 49 undergraduate nursing students enrolled in 2018. The same teaching staff were assigned to both groups. Geriatric Nursing was taught in the intervention group using a teaching model based on metacognition from April to June 2022, while the control group was taught using the traditional teaching model from April to June 2021. Student satisfaction and teaching effectiveness in the intervention group were assessed using a self-designed teaching evaluation questionnaire. SPSS 25.0 software was used for two-sample t test. Results:The intervention and control groups showed individual assignment scores of (85.33±5.96) and (82.36±7.25) and total scores of (84.44±4.31) and (82.61±5.05), respectively. The individual assignment score of the intervention group was significantly higher than that of the control group, while there was no significant difference in the total score. In terms of satisfaction, over 90% of the students in the intervention group expressed satisfaction with the teaching model. The item with the highest proportion of students rating it as "very good" was "being required to submit a plan for completing individual assignments in advance" ( n=32, 76.19%). In terms of teaching effectiveness, all students recognized the teaching effectiveness of this course. Conclusions:It is necessary to adopt the teaching model based on metacognitive strategies in teaching Geriatric Nursing for undergraduates, which can significantly promote their individual assignment performance as well as the evaluation of teaching strategies and teaching effectiveness.

Objective:To preliminarily explore therapeutic effects and possible molecular mechanisms of sinomenine on atopic dermatitis (AD) -like mouse models.Methods:Thirty female BALB/c mice (6 - 8 weeks old) were randomly divided into 5 groups: blank control group, model group, positive control group, topical sinomenine group, and oral sinomenine group. Except for the blank control group, all groups were subjected to repeated topical stimulation with 2,4-dinitrochlorobenzene (DNCB) on the dorsal skin to establish an AD-like mouse model. After modeling, no special treatment was given to the blank control group, the positive control group was topically treated with 100 μg of 0.1% mometasone furoate cream twice daily on the lesions, the topical sinomenine group was topically treated with 100 μl of 10 mg/ml sinomenine solution twice daily on the lesions, and the oral sinomenine group was gavaged with sinomenine solution at a dose of 100 mg·kg -1·d -1 (100 μl per dose, twice daily) . Treatments lasted for 14 days. Twelve hours after the final treatment, the severity of skin lesions in each group was assessed. Blood samples were collected via enucleation, and serum levels of interleukin (IL) -1β, IL-6, and immunoglobulin E (IgE) were measured using enzyme-linked immunosorbent assay (ELISA) . Histopathological changes in dorsal skin lesions were observed, and immunohistochemical study was performed to detect the expression levels of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF) -κB p65 in skin tissues, expressed as the percentage of the immunopositive area. One-way analysis of variance was used for multiple group comparisons, while Tukey′s test or the Games-Howell test was applied for post-hoc comparisons between groups. Results:Compared with the blank control group, the model group exhibited epidermal hyperkeratosis with parakeratosis, thickening of the spinous layer, spongiosis, significant inflammatory cell infiltration, and prominent angiogenesis. In contrast, the positive control group, topical sinomenine group, and oral sinomenine group showed reduced spinous layer thicknesses, decreased inflammatory cell infiltration, and less pronounced angiogenesis compared to the model group. In the blank control group, model group, positive control group, topical sinomenine group, and oral sinomenine group, the severity scores of skin lesions were 0, 8.83 ± 0.75, 4.33 ± 1.08, 2.58 ± 0.49, 2.83 ± 0.93 respectively, the serum levels of IL-1β were 52.58 ± 1.72, 168.40 ± 7.23, 57.07 ± 6.39, 85.74 ± 4.15, 100.30 ± 11.55 pg/ml respectively, IL-6 levels were 86.88 ± 4.60, 215.00 ± 5.02, 79.34 ± 4.91, 127.20 ± 1.06, 149.00 ± 6.21 pg/ml respectively, IgE levels were 2 159.00 ± 176.00, 3 493.00 ± 89.61, 2 294.00 ± 158.10, 2 550.00 ± 214.70, 2 814.00 ± 119.70 μg/ml respectively, the expression levels of p38 MAPK in skin tissues were 3.03% ± 3.38%, 12.95% ± 6.89%, 2.14% ± 1.28%, 5.28% ± 3.71%, 3.85% ± 2.26% respectively, and NF-κB p65 expression levels were 0.61% ± 0.49%, 18.92% ± 6.96%, 3.77% ± 1.90%, 5.66% ± 2.28%, 6.25% ± 3.14% respectively; the differences in all the above parameters were statistically significant among groups (all P < 0.05) . Compared with the blank control group, the model group had significantly increased skin lesion severity scores, serum IL-1β, IL-6, and IgE levels, as well as elevated expression of p38 MAPK and NF-κB p65 in skin tissues (all P < 0.01) . Compared with the model group, the positive control group, topical sinomenine group, and oral sinomenine group showed significantly reduced skin lesion severity scores, decreased serum IL-1β, IL-6, and IgE levels, and lower expression of p38 MAPK and NF-κB p65 in skin tissues (all P < 0.05) . Compared with the positive control group, the topical and oral sinomenine groups exhibited further reductions in skin lesion severity scores (both P < 0.05) . Additionally, the topical sinomenine group showed significantly lower serum levels of IL-1β and IL-6 compared with the oral sinomenine group (both P < 0.05) . Conclusion:Sinomenine solution could obviously alleviate the severity of skin lesions in AD-like mouse models, likely by down-regulating the expression of IL-1β, IL-6 and IgE, inhibiting the MAPK/NF-κB signaling pathway, and thus reducing the degree of inflammation.

Objective:To construct a teaching model for Geriatric Nursing based on metacognitive strategy and to test its effectiveness in teaching undergraduate nursing students.Methods:A quasi-experimental research design was adopted. The intervention group consisted of 49 undergraduate nursing students enrolled in 2019 at Sun Yat-sen University, while the control group was made up of 49 undergraduate nursing students enrolled in 2018. The same teaching staff were assigned to both groups. Geriatric Nursing was taught in the intervention group using a teaching model based on metacognition from April to June 2022, while the control group was taught using the traditional teaching model from April to June 2021. Student satisfaction and teaching effectiveness in the intervention group were assessed using a self-designed teaching evaluation questionnaire. SPSS 25.0 software was used for two-sample t test. Results:The intervention and control groups showed individual assignment scores of (85.33±5.96) and (82.36±7.25) and total scores of (84.44±4.31) and (82.61±5.05), respectively. The individual assignment score of the intervention group was significantly higher than that of the control group, while there was no significant difference in the total score. In terms of satisfaction, over 90% of the students in the intervention group expressed satisfaction with the teaching model. The item with the highest proportion of students rating it as "very good" was "being required to submit a plan for completing individual assignments in advance" ( n=32, 76.19%). In terms of teaching effectiveness, all students recognized the teaching effectiveness of this course. Conclusions:It is necessary to adopt the teaching model based on metacognitive strategies in teaching Geriatric Nursing for undergraduates, which can significantly promote their individual assignment performance as well as the evaluation of teaching strategies and teaching effectiveness.

Sedentary bad habits and unhealthy diets in modern lifestyles have led to an upward trend in the incidence of obesity, and a series of diseases related to obesity have also gradually received attention. Multiple sclerosis is a chronic inflammatory disease of the central nervous system, and obesity has a common inflammatory component with most chronic diseases. Therefore, this paper reviews the research progress on the relationship between obesity and multiple sclerosis in order to better understand the role of obesity in the management of multiple sclerosis.

Background: Cervical cancer is still present a major public health problem, especially in developing countries. In International Federation of Gynaecology and Obstetrics 2018, allowing assessment of retroperitoneal lymph nodes by imaging and/or pathological findings and, if deemed metastatic, the case is designated as stage IIIC (with r and p notations). Patients with lymph node metastases have lower overall survival (OS), progression free survival (PFS), and survival after recurrence, especially those who have unresectable macroscopical positive lymph nodes. Retrospective analysis suggests that there may be a benefit to debulking macroscopic nodes that would be otherwise difficult to sterilize with standard doses of radiation therapy. However, there are no prospective study reporting that resecting macroscopic nodes before concurrent chemoradiation therapy (CCRT) would improve PFS or OS of cervical cancer and no guidelines for surgical resection of bulky lymph nodes. The CQGOG0103 study is a prospective, multicenter and randomized controlled trial (RCT) evaluating lymph node dissection on stage IIICr of cervical cancer. Methods Eligible patients are histologically confirmed cervical squamous cell carcinoma, adenocarcinoma, adeno-squamous cell carcinoma. Stage IIICr (confirmed by computed tomography [CT]/magnetic resonance imaging/positron emission tomography/CT) and the short diameter of image-positive lymph node ≥15 mm. 452 patients will be equally randomized to receive either CCRT (pelvic external-beam radiotherapy [EBRT]/extended-field EBRT + cisplatin [40 mg/m2] or carboplatin [the area under curve=2] every week for 5 cycles + brachytherapy) or open/minimally invasive pelvic and para-aortic lymph node dissection followed by CCRT. Randomization is stratified by status of para-aortic lymph node. The primary endpoint is PFS. Secondary endpoints are OS and surgical complications. A total of 452 patients will be enrolled from multiple hospitals in China within 4 years and followed up for 5 years.

BACKGROUND: The occurrence and development of lung cancer are closely linked to epigenetic modification. Abnormal DNA methylation in the CpG island region of genes has been found in many cancers. Protein kinase C delta binding protein (PRKCDBP) is a potential tumor suppressor and its epigenetic changes are found in many human malignancies. This study investigated the possibility of PRKCDBP methylation as a potential biomarker for non-small cell lung cancer (NSCLC). METHODS: We measured the methylation levels of PRKCDBP in the three groups of NSCLC tissues. Promoter activity was measured by the dual luciferase assay, with 5'-aza-deoxycytidine to examine the effect of demethylation on the expression level of PRKCDBP. RESULTS: The methylation levels of PRKCDBP in tumor tissues and 3 cm para-tumor were higher than those of distant (>10 cm) non-tumor tissues. Receiver operating characteristic (ROC) curve analysis between tumor tissues and distant non-tumor tissues showed that the area under the line (AUC) was 0.717. Dual luciferase experiment confirmed that the promoter region was able to promote gene expression. Meanwhile, in vitro methylation of the fragment (PRKCDBP_Me) could significantly reduce the promoter activity of the fragment. Demethylation of 5'-aza-deoxycytidine in lung cancer cell lines A549 and H1299 showed a significant up-regulation of PRKCDBP mRNA levels. CONCLUSIONS PRKCDBP methylation is a potential and promising candidate biomarker for non-small cell lung cancer.
Biomarkers/metabolism* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Cell Line, Tumor ; DNA Methylation ; Gene Expression Regulation, Neoplastic ; Humans ; Intracellular Signaling Peptides and Proteins/genetics* ; Lung Neoplasms/pathology* ; Promoter Regions, Genetic

Objective:To analyze the efficacy and safety of adalimumab in the treatment of pediatric inflammatory bowel disease (IBD) patients.Methods:Clinical data of pediatric IBD patients who switched to adalimumab therapy after the failure of infliximab in the Children′s Hospital, Zhejiang University School of Medicine from January 2019 to September 2020 were analyzed retrospectively. A descriptive method was used to analyze the general information, disease activity index and mucosal inflammation before and after the treatment of adalimumab. The pediatric Crohn′s disease activity index (PCDAI) and pediatric ulcerative colitis activity index (PUCAI) were used to evaluate the disease activity. The Crohn′s disease endoscopic index of severity (CDEIS) and ulcerative colitis endoscopic index of severity (UCEIS) were used to evaluate the mucosal inflammation.Results:A total of 10 children diagnosed with IBD were treated with adalimumab, including 9 patients of Crohn′s disease (CD) and 1 of ulcerative colitis (UC) . There were 6 males and 4 females, with disease onset age of 0.3 to 13.3 years and median duration of 38 (3 to 81) months before the treatment of adalimumab. In lesion location of 9 CD patients, 2 patients only involved the small intestine (L4a+L4b) and 7 patients involved the whole digestive tract (L3+L4a+L4b) according to Paris classification. The reasons of switching infliximab to adalimumab were as follows: primary loss response to infliximab occurred in 1 patient, secondary loss response to infliximab in 6 and severe anaphylaxis in 3. According to PCDAI and PUCAI, the clinical remission was achieved in 1, mild activity in 4, moderate in 3 and severe in 2 before the treatment of adalimumab. Clinical remission was achieved in 6, clinical response in 1 and non-response in 1 at the 10th week. After the median follow-up period of 25 (10 to 86) weeks, clinical remission was achieved in 8, the clinical symptom of 1 non-responsive patient was improved during the follow-up. The left 1 non-responsive patient stopped treatment of adalimumab and received gene sequencing test, and the results showed a hemizygote mutation of X-linked inhibitor of apoptosis protein ( XIAP) gene and the X-linked lymphocytic proliferation syndrome was considered. Five cases of side reaction occurred in 10 patients, mainly the respiratory infections, and no other serious side reactions occurred. Conclusion:Switching to adalimumab attains good outcome in pediatric IBD patients after the failure of infliximab.

Objective:To evaluate the difference of dosimetry between three-dimensional and two-dimensional plans based on CT images of occult perforation in brachytherapy of cervical cancer, aiming to provide clinical reference.Methods:A total of 817 patients with cervical cancer received simple intrauterine (intrauterine tandem plus vaginal colpostats) three-dimensional brachytherapy in Chongqing University Cancer Hospital from January 2019 to December 2020 were retrospectively reviewed. Among them, 16 patients had occul uterine perforation. Based on Oncentra Brachy Therapy plan system, the single prescription dose was 6Gy. Three-dimensional (3D group) and two-dimensional (2D group) plans were designed on the perforated CT images The target volume, conformal index (CI), conformal index coformity index (COIN) and organs-at-risk (OAR) D 2cm 3 parameters were used to assess the plans between two groups. Results:The incidence of pccult uterine perforation was 1.96%(16/817) during brachytherapy for cervical cancer. The volume of prescription dose curve in the 3D group was (40.74±14.98) cm 3, significantly smaller compared with (91.46±19.71) cm 3 in the 2D group ( P<0.05), whereas the volume of the high-risk clinical target area wrapped by prescription dose curve did not significantly differ between two groups ( P>0.05). The CI and COIN in the 3D group were 0.79±0.10 and 0.72±0.96, significantly higher compared with 0.38±0.09 and 0.37±0.18 in the 2D group (both P<0.05). The D 2cm 3 of bladder, rectum, sigmoid colon, small intestine in the 3D group were (306.06±77.57) cGy, (252.27±72.60) cGy, (127.25±62.84) cGy and (228.79±94.90) cGy, significantly lower than (548.03±164.21) cGy, (411.16±118.74) cGy, (227.45±94.48) cGy and (450.95±157.96) cGy in the 2D group (all P<0.05). Conclusions:Application of image guidance in brachytherapy of cervical cancer is helpful to detect occult uterine perforation. When occult uterine perforation occurs, the use of three-dimensional plan can basically meet the clinical needs, which is significantly better than the two-dimensional plan.

Objective:To analyze the efficacy and safety of adalimumab in the treatment of pediatric inflammatory bowel disease (IBD) patients.Methods:Clinical data of pediatric IBD patients who switched to adalimumab therapy after the failure of infliximab in the Children′s Hospital, Zhejiang University School of Medicine from January 2019 to September 2020 were analyzed retrospectively. A descriptive method was used to analyze the general information, disease activity index and mucosal inflammation before and after the treatment of adalimumab. The pediatric Crohn′s disease activity index (PCDAI) and pediatric ulcerative colitis activity index (PUCAI) were used to evaluate the disease activity. The Crohn′s disease endoscopic index of severity (CDEIS) and ulcerative colitis endoscopic index of severity (UCEIS) were used to evaluate the mucosal inflammation.Results:A total of 10 children diagnosed with IBD were treated with adalimumab, including 9 patients of Crohn′s disease (CD) and 1 of ulcerative colitis (UC) . There were 6 males and 4 females, with disease onset age of 0.3 to 13.3 years and median duration of 38 (3 to 81) months before the treatment of adalimumab. In lesion location of 9 CD patients, 2 patients only involved the small intestine (L4a+L4b) and 7 patients involved the whole digestive tract (L3+L4a+L4b) according to Paris classification. The reasons of switching infliximab to adalimumab were as follows: primary loss response to infliximab occurred in 1 patient, secondary loss response to infliximab in 6 and severe anaphylaxis in 3. According to PCDAI and PUCAI, the clinical remission was achieved in 1, mild activity in 4, moderate in 3 and severe in 2 before the treatment of adalimumab. Clinical remission was achieved in 6, clinical response in 1 and non-response in 1 at the 10th week. After the median follow-up period of 25 (10 to 86) weeks, clinical remission was achieved in 8, the clinical symptom of 1 non-responsive patient was improved during the follow-up. The left 1 non-responsive patient stopped treatment of adalimumab and received gene sequencing test, and the results showed a hemizygote mutation of X-linked inhibitor of apoptosis protein ( XIAP) gene and the X-linked lymphocytic proliferation syndrome was considered. Five cases of side reaction occurred in 10 patients, mainly the respiratory infections, and no other serious side reactions occurred. Conclusion:Switching to adalimumab attains good outcome in pediatric IBD patients after the failure of infliximab.