Skin aging is a complex physiological process that is associated with various skin diseases and affects appearance.Vitamin D, a fat-soluble vitamin synthesized after exposure of the skin to ultraviolet B radiation, has been found to regulate skin aging by modulating the physiological functions of skin cells, regulating the immune system, inducing antioxidative responses, inhibiting DNA damage, and promoting its repair. This article elucidates the multi-target mechanism of vitamin D in delaying skin aging, providing a new theoretical foundation for preventive medicine to retard aging and related diseases through nutritional intervention.

Skin aging is a complex physiological process that is associated with various skin diseases and affects appearance.Vitamin D, a fat-soluble vitamin synthesized after exposure of the skin to ultraviolet B radiation, has been found to regulate skin aging by modulating the physiological functions of skin cells, regulating the immune system, inducing antioxidative responses, inhibiting DNA damage, and promoting its repair. This article elucidates the multi-target mechanism of vitamin D in delaying skin aging, providing a new theoretical foundation for preventive medicine to retard aging and related diseases through nutritional intervention.

Objective To study the value of serum annexin A1(ANXA1)and annexin A2(ANXA2)in the evaluation of platinum-based chemotherapy resistance in patients with epithelial ovarian cancer(EOC)and their relationship with prognosis.Methods A total of 125 EOC patients who were admitted to Handan First Hospital from June 2017 to June 2020 were selected.According to the chemotherapy efficacy,patients were di-vided into sensitive group(81 cases)and drug-resistant group(44 cases).The clinical data,serum ANXA1 and ANXA2 levels were compared between two groups.The influencing factors of platinum-based chemother-apy resistance in EOC patients were analyzed by multivariate Logistic regression model.The value of serum ANXA1 and ANXA2 in predicting platinum-based chemotherapy resistance in EOC patients were analyzed by receiver operating characteristic curve.The prognosis of EOC patients was analyzed by Kaplan-Meier survival curve.Results A total of 125 patients completed surgery+platinum-based chemotherapy,there were 81 cases in sensitive group and 44 cases in drug-resistant group.Compared with sensitive group,the proportion of FI-GO stage Ⅲ-Ⅳ,the proportion of lymph node metastasis,serum ANXA2 level in drug-resistant group were significantly increased(P＜0.05),and serum ANXA1 level was significantly decreased(P＜0.05).Elevated serum ANXA2 level and decreased serum ANXA1 level were risk factors for platinum-based chemotherapy re-sistance in EOC patients(P＜0.05).The area under the curve of serum ANXA1 and ANXA2 alone or in com-bination for predicting platinum-based chemotherapy resistance in EOC patients was 0.687(95％CI:0.405-0.973),0.763(95％CI:0.618-0.901),0.832(95％CI:0.720-0.948)respectively,and the predictive effica-cy of combined detection of serum ANXA1 and ANXA2 was better than that of single detection(P＜0.05).Kaplan-Meier survival curve showed that the 3-year overall survival rate in ANXA1 low expression group was significantly lower than that in ANXA1 high expression group(P＜0.05),and the 3-year overall survival rate in ANXA2 high expression group was significantly lower than that in ANXA2 low expression group(P＜0.05).Conclusion The decrease of serum ANXA1 level and the increase of ANXA2 level are related to plati-num-based chemotherapy resistance and poor prognosis in EOC patients,which are expected to be used as ear-ly warning indicators to predict platinum-based chemotherapy resistance.

ObjectiveTo investigate the antidepressant effect of Sinisan （SNS） by regulating glycogen aynthase kinase-3β （GSK-3β）/tumor necrosis factor alpha-induced protein 3（A20）/CCAAT enhancer binding protein β（C/EBPβ） to inhibit the activation of microglia. MethodA total of 72 male C57/6J mice were randomly divided into the normal group， model group， fluoxetine group （5.0 mg·kg^-1）， low-dose Sinisan group （4.9 g·kg^-1）， medium-dose Sinisan group （9.8 g·kg^-1）， and high-dose Sinisan group （19.6 g·kg^-1）， with 12 mice in each group. After one week of adaptive feeding， chronic unpredictable mild stress （CUMS） was performed to establish the depression model. In the fifth week， drug treatment was conducted for four weeks. In the ninth week， behavioral tests were performed， including sucrose preference test （SPT）， open field test （OPT）， elevated plus maze （EPM） test， and forced swimming test （FST）. Western blot was used to detect the expression levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， nitric oxide synthase （iNOS）， GSK-3β， A20， and C/EBPβ in the cortex. The expression of M1-polarized ionized calcium-binding adapter molecule 1 （Iba1） and cluster of differentiation 68 （CD68） in microglia was detected by immunofluorescence. ResultAfter eight weeks of CUMS， compared with the normal group， the mice in the model group had a significantly reduced sucrose preference rate （P<0.01）， and the activity in the central area of the OPT was significantly reduced （P<0.01）. The activity in the open arm area of the EPM test was significantly reduced （P<0.05）， and the immobility time of FST was increased （P<0.01）. The expression levels of inflammatory proteins IL-1β， IL-6， and iNOS were increased （P<0.01）， and the fluorescence co-localization index of Iba1 and CD68 was increased （P<0.05）. The protein expression levels of GSK-3β and C/EBPβ were significantly increased （P<0.05， P<0.01）. After four weeks of SNS intervention， compared with the model group， the mice in the SNS group had significantly increased sucrose preference rate （P<0.01）， significantly increased activities in the central area and the open arm area in the OPT and the EPM test （P<0.05）， and significantly reduced immobility time in the FST （P< 0.01）. The protein expression levels of IL-1β， IL-6， and iNOS were significantly decreased （P<0.05）， and the fluorescence co-localization index of Iba1 and CD68 was decreased in the high-dose SNS group （P<0.05）. The protein expression levels of GSK-3β and C/EBPβ in the medium-dose and high-dose SNS groups were significantly decreased （P<0.01）， and that of A20 was significantly increased （P<0.01）. ConclusionThe antidepressant effect of SNS is related to the regulation of GSK-3β/A20/C/EBPβ protein expression and the inhibition of M1-type activation of microglia.

Objective:The common protocol deviation (PD) in clinical trials of drugs for rheumatic diseases were analyzed to provide reference for improving the quality of clinical trials and protecting the safety and rights of subjects.Methods:Protocol deviation (PD) reports of completed projects conducted by Department of Rheumatology and Immunology, the Second Hospital of Shanxi Medical University, from 2017 to 2021 were collected and sorted out for analysis. Results:The common PD and proportion of deviation were deviation from protocol study procedures (25.4%, 44/173), low medication compliance (23.7%, 41/173), visits out of the scheduled visit dates or the tests or examinations out od the inspection window period (19.1%, 33/173), missed visit or missed laboratory tests (17.9%, 31/174), using of prohibited drugs (9.2%, 16/173) and violation of inclusion criteria or exclusion criteria (4.6%, 8/173). 135 cases were mild and 38 cases severe deviation. PPS was eliminated in 5 subjects during statistical analysis.Conclusion:①Investigator training should be strengthened and the operability should be taken into account in clinical trial design. In the implementation process, the inclusion and exclusion criteria should be strictly followed and the should adherent to study procedures. ②The institution should actively promote the development of hospital information system to reduce investigator associated PD. ③The education and management of subject should be strengthened to ensure their compliance and improve the quality of clinical trials to protect the safety and rights of subjects. ④Institute should strengthen the management of trail supervisors and emphasis on problems identification during inspections.

AIM: To investigate the relationship between TRPM3 and diabetes-induced painful peripheral neuropathy. METHODS: Treptozotocin (STZ) was intraperitoneal injected for establishment of diabetic mice model, behavioral tests of paw withdraw thresholds (PWTs) and paw withdraw latencies (PWLs) were conducted; Protein contents and tyrosine phosphorylation levels of TRPM3 were detected by immunoprecipitation and immunoblotting. RESULTS: The PWTs and PWLs in diabetic mice were significantly reduced; TRPM3 tyrosine phosphorylation in the dorsal root ganglia (DRG) of diabetic mice significantly increased compared with control, while the protein expression shows no statistical significance; Enhanced tyrosine phosphorylation of TRPM3 by BPV can evoke heat hyperalgesia in intact mice; Reduce of the tyrosine phosphorylation levels of TRPM3 through PP2 significantly alleviates diabetes-induced heat hyperalgesia, without affecting mechanical allodynia. CONCLUSION: The upregulation of tyrosine phosphorylation of TRPM3 plays a key role in heat related painful diabetic peripheral neuropathy.

Autoantibody-related congenital heart block (ACHB) is a passively acquired autoimmune disease developing in fetuses after exposuring to maternal anti-Ro/Sj?gren's syndrome type A (SSA) antibody and/or anti-La/SSB antibody transported across the placenta, which contributes to fetal heart conduction system damage and signal conduction block at the atrioventricular node. However, fetal atrioventricular block does not necessarily occur with the presence of maternal autoantibodies, indicating its complex pathogenesis. This review focuses on the theories of calcium channels and apoptosis, the influence of other maternal factors and environmental changes on ACHB and the roles of natural killer cells and human leukocyte antigen in ACHB, aiming to provide reference for further study on the pathogenesis.

Objective:To explore the correlation between urine Alzheimer disease associated neuronal thread protein (AD7C-NTP) and cognitive dysfunction in patients with Parkinson disease (PD).Methods:The clinical data of 90 patients with PD in Weihai Central Hospital in Shandong Province from April 2016 to August 2019 were retrospectively analyzed. According to the Montreal cognitive assessment scale (MoCA) score, the patients were divided into non cognitive impairment group (46 cases) and mild cognitive impairment group (44 cases). Forty-five healthy persons matched in gender and age were selected as control group. The urine AD7C-NTP, and serum homocysteine (Hcy), uric acid, C-reactive protein (CRP) were detected. The MoCA score, PD Hoehn-Yahr classification (H-Y classification), levodopa equivalent dose and time of taking medicine were record. The correlation between AD7C-NTP and various clinical indicators was analyzed by Pearson method. Risk factors of cognitive dysfunction in patients with PD were analyzed by Logistic regression.Results:The AD7C-NTP and Hcy in mild cognitive impairment group were significantly higher than those in control group and non cognitive impairment group: (3.3 ± 2.3) μg/L vs. (1.9 ± 1.6) and (2.1 ± 2.0) μg/L, (13.5 ± 3.4) μmol/L vs. (9.1 ± 4.5) and (11.0 ± 3.1) μmol/L, the indexes in non cognitive impairment group were significantly higher than those in control group, and there were statistical differences ( P<0.05). The uric acid in mild cognitive impairment group was significantly lower than that in control group and non cognitive dysfunction group: (286.7 ± 62.9) μmol/L vs. (338.6 ± 70.4) and (322.9 ± 81.2) μmol/L, the index in non cognitive impairment group was significantly lower than that in control group, and there were statistical differences ( P<0.05). The MoCA score in mild cognitive impairment group was significantly lower than that in non cognitive impairment group: (22.9 ± 2.9) scores vs. (27.3 ± 2.4) scores, the H-Y classification, levodopa equivalent dose and time of taking medicine were significantly higher than those in non cognitive impairment group: (2.7 ± 0.7) stages vs. (2.4 ± 0.6) stages, (465.8 ± 132.1) mg/d vs. (405.8 ± 139.5) mg/d and (46.9 ± 22.1) months vs. (35.8 ± 24.4) months, and there were statistical differences ( P < 0.01 or<0.05). Pearson correlation analysis result showed that AD7C-NTP was negatively correlated with uric acid and MoCA scores ( r = -0.365 and -0.586, P < 0.01), and positively correlated with H-Y classification, levodopa equivalent, Hcy and time of taking medicine ( r = 0.568, 0.434, 0.362 and 0.324; P < 0.01). Multivariate Logistic regression analysis result showed that AD7C-NTP, Hcy and H-Y classification were independent risk factors of cognitive dysfunction in patients with PD ( P < 0.01 or<0.05), and uric acid was an independent protective factor ( P < 0.05). Conclusions:The expression of urine AD7C-NTP is increased in PD patients with cognitive impairment. The level of urine AD7C-NTP is correlated with cognitive impairment and disease severity, which may be an effective biomarker of cognitive impairment in PD patients.

Objective:To explore the application value of contrast-enhanced ultrasound with SonoLiver software including quantitative analysis and dynamic vascular pattern (DVP) in the intraoperative diagnosis of glioma.Methods:SonoLiver software was used to analyze the contrast-enhanced ultrasound (CEUS) process of 252 cases with different grades of gliomas in General Hospital of Southern Theatre Command of PLA from 2006 to 2016. Among them, 144 were in the low-grade gliomas (LGG) group and 108 were in the high-grade gliomas (HGG) group. The quantitative parameters included maximum intensity (IMAX), time to peak (TTP) and mean transit time (mTT). The images of each CEUS were obtained, and the microvessel density (MVD) of corresponding pathology was compared, so as to analyze their correlations and characteristics.Results:There were significant differences in IMAX, TTP and mTT between the CEUS parameters of gliomas with different grades. IMAX in HGG group was significantly higher than that in LGG group( P<0.001), while TTP was shorter ( P=0.017) and mTT was longer( P=0.030). By correlation analysis between MVD and the CEUS parameters, MVD was positively correlated with IMAX ( r s=0.736, P<0.001) and mTT( r s=0.184, P=0.003), but negatively correlated with TTP( r s=-0.186, P=0.003). Compared with DVP images, the tumor areas of LGG group were mainly warm and black colors with small spots of cool-colored areas, and most of the surrounding areas were more obvious black areas. In HGG group, the tumor areas were mainly warm colors. Most of which were scattered in patchy cold colors areas, and the surrounding black areas were less ( P<0.05). There were significant differences in differentiating gliomas boundary before and after using DVP technique ( P<0.05). After using DVP, the boundary of glioma was clearer and more discernible. The discernibility of HGG group was up to 99%, and that of LGG group reached 97%. Conclusions:SonoLiver software can effectively and quantitatively analyze the CEUS parameters of gliomas with different grades, and its DVP images can directly reflect the contrast perfusion characteristics of gliomas, providing a new way to distinguish the boundary of gliomas and a new imaging method for the differential diagnosis of high and low grades of gliomas.

Objective:To develop scientific and practical sensitive indicators with its own characteristics for nursing quality of breast specialty.Methods:A research team was established in August 2018, which searched the databases both at home and abroad, screened and identified relevant literatures according to John Hopkins' evidence level and quality evaluation standards. A sensitive indicator framework for nursing quality of breast specialty was preliminarily formed based on the indicators involved in the literatures. In January 2019, the expert correspondence questionnaire was prepared. Twenty experts were randomly selected from the Qingdao Medical Doctors Association and the Nursing Experts Committee and received two rounds of correspondence consultations using the Delphi method in order to build, modify and confirm the sensitive indicator system for nursing quality of breast specialty.Results:The authority coefficients of the experts in the two rounds of consultation were 0.815 and 0.858; the expert authority coefficient was> 0.80; and the coefficient of variation of each indicator was< 0.30. Eleven sensitive indicators for nursing quality of breast specialty including the awareness rate of functional exercise of the affected limb and lymphedema prevention measures were developed.Conclusions:The sensitive indicators of nursing quality of breast specialty based on the Delphi method is highly practical and credible, which have distinctive specialty characteristics, may be used for the overall care quality assessment and management of breast disease patients, and provide accurate and scientific evaluation for clinical nursing work.