cAMP-Epac1 signaling is activated in DDAVP-induced endolymphatic hydrops of guinea pigs

Abstract Objective To explore whether Cyclic Adenosine Monophosphate (cAMP)-Epac1 signaling is activated in 1-Desamino-8-D-arginine-Vasopressin-induced Endolymphatic Hydrops (DDAVP-induced EH) and to provide new insight for further in-depth study of DDAVP-induced EH. Methods Eighteen healthy, red-eyed guinea pigs (36 ears) weighing 200-350 g were randomly divided into three groups: the control group, which received intraperitoneal injection of sterile saline (same volume as that in the other two groups) for 7 consecutive days; the DDAVP-7d group, which received intraperitoneal injection of 10 mg/mL/kg DDAVP for 7 consecutive days; and the DDAVP-14d group, which received intraperitoneal injection of 10 μg/mL/kg DDAVP for 14 consecutive days. After successful modeling, all animals were sacrificed, and cochlea tissues were collected to detect the mRNA and protein expression of the exchange protein directly activated by cAMP-1 and 2 (Epac1, Epac2), and Repressor Activator Protein-1 (Rap1) by Reverse Transcription (RT)-PCR and western blotting, respectively. Results Compared to the control group, the relative mRNA expression of Epac1, Epac2, Rap1A, and Rap1B in the cochlea tissue of the DDAVP-7d group was significantly higher (p< 0.05), while no significant difference in Rap1 GTPase activating protein (Rap1gap) mRNA expression was found between the two groups. The relative mRNA expression of Epac1, Rap1A, Rap1B, and Rap1gap in the cochlea tissue of the DDAVP-14d group was significantly higher than that of the control group (p< 0.05), while no significant difference in Epac2 mRNA expression was found between the DDAVP-14d and control groups. Comparison between the DDAVP-14d and DDAVP-7d groups showed that the DDAVP-14d group had significantly lower Epac2 and Rap1A (p< 0.05) and higher Rap1gap (p < 0.05) mRNA expression in the cochlea tissue than that of the DDAVP-7d group, while no significant differences in Epac1 and Rap1B mRNA expression were found between the two groups. Western blotting showed that Epac1 protein expression in the cochlea tissue was the highest in the DDAVP-14d group, followed by that in the DDAVP-7d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); Rap1 protein expression in the cochlea tissue was the highest in the DDAVP-7d group, followed by the DDAVP-14d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); no significant differences in Epac2 protein expression in the cochlea tissue were found among the three groups. Conclusion DDAVP upregulated Epac1 protein expression in the guinea pig cochlea, leading to activation of the inner ear cAMP-Epac1 signaling pathway. This may be an important mechanism by which DDAVP regulates endolymphatic metabolism to induce EH and affect inner ear function. Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Level 5.

Correction of the pathogenic mutation in the G6PC3 gene by adenine base editing in mutant embryos / 中华血液学杂志

Objective: To determine whether the adenine base editor (ABE7.10) can be used to fix harmful mutations in the human G6PC3 gene. Methods: To investigate the safety of base-edited embryos, off-target analysis by deep sequencing was used to examine the feasibility and editing efficiency of various sgRNA expression vectors. The human HEK293T mutation models and human embryos were also used to test the feasibility and editing efficiency of correction. Results: ①The G6PC3(C295T) mutant cell model was successfully created. ②In the G6PC3(C295T) mutant cell model, three distinct Re-sgRNAs were created and corrected, with base correction efficiency ranging from 8.79% to 19.56% . ③ ABE7.10 could successfully fix mutant bases in the human pathogenic embryo test; however, base editing events had also happened in other locations. ④ With the exception of one noncoding site, which had a high safety rate, deep sequencing analysis revealed that the detection of 32 probable off-target sites was <0.5% . Conclusion: This study proposes a new base correction strategy based on human pathogenic embryos; however, it also produces a certain nontarget site editing, which needs to be further analyzed on the PAM site or editor window.

Iodine nutritional status of children and pregnant women in 37 coastal counties (cities and districts) of Shandong Province in 2021 / 中华地方病学杂志

Objective:To learn about the prevalence of iodized salt in coastal counties (cities and districts, hereinafter referred to as counties) of Shandong Province, evaluate the iodine nutritional status of children and pregnant women, so as to provide data support for timely targeted prevention and control measures and scientific adjustment of intervention strategies.Methods:In 2021, in 37 coastal counties of Shandong Province, one township was selected from each of the five directions of the east, west, south, north, and middle of each county, one primary school was selected from each township, 40 non-boarding students aged 6 - 12 years old were selected from each primary school. In addition, 20 pregnant women were selected from each township. Children's and pregnant women's household salt samples and urine samples were collected to detect salt iodine and urinary iodine contents. The children from 19 counties selected from the 37 coastal counties of Shandong Province were examined by B-mode ultrasound, and the goiter rate of children was calculated.Results:Totally 7 736 household edible salt samples from the children were tested, and the coverage rate of iodized salt, iodized salt qualified rate and qualified iodized salt consumption rate was 74.3% (5 746/7 736), 74.3% (4 267/5 746) and 55.2% (4 267/7 736), respectively. A total of 7 740 urine samples were collected from the children, the median urinary iodine was 174.0 μg/L. A total of 4 344 children were selected for thyroid examination, and the goiter rate was 3.0% (131/4 344). Totally 4 513 household edible salt samples from the pregnant women were tested, and the coverage rate of iodized salt, iodized salt qualified rate and qualified iodized salt consumption rate was 83.7% (3 779/4 513), 77.6% (2 933/3 779) and 65.0% (2 933/4 513), respectively. A total of 7 740 urine samples were collected from the pregnant women, the median urinary iodine was 133.5 μg/L.Conclusions:Children in 37 coastal counties of Shandong Province are generally at the appropriate level of iodine, but pregnant women still have the risk of iodine deficiency. Comprehensive prevention and control measures for iodine deficiency disorders need to be continuously implemented to consolidate and deepen the achievements of iodine deficiency prevention and control.

The effect of water improvement on iodine nutritional status and thyroid function of pregnant women in areas with high water iodine level / 中华地方病学杂志

Objective:To investigate the impact of switching to low iodine drinking water in areas with high water iodine levels on the iodine nutritional status and thyroid function of pregnant women.Methods:A cross-sectional survey was conducted in Gaoqing County, Zibo City, Shandong Province. Pregnant women who underwent prenatal examinations at the Obstetrics Clinic of Gaoqing County People's Hospital from 2019 to 2021 were selected as the survey subjects. With reference to the Criteria for the Classification of Water Source High Iodine Areas and High Iodine Disease Areas (GB/T 19380-2016), pregnant women with drinking water iodine > 100 μg/L were considered as the high water iodine group and ≤100 μg/L was the non-high water iodine group. Basic information, one random urine sample, fasting blood sample, 24-hour urine sample and drinking water sample of pregnant women were collected, and thyroid ultrasound examination was performed on pregnant women. Urinary iodine (UI) concentration (UIC) and drinking water iodine concentration (WIC) were measured by inductively coupled plasma mass spectrometry, and 24-hour urinary iodine excretion (UIE) and daily iodine intake (TII) of pregnant women were calculated. Serum thyroid hormone (TSH), free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid peroxidase antibody (TPOAb) and anti-thyroid autoantibodies (TgAb) were determined by automatic chemiluminescence immunoassay. Creatinine (CR) was determined using deproteinized endpoint microplate method and UI/CR was calculate. Results:A total of 797 pregnant women were included, and the UIC was 150.2 (88.1, 281.3) μg/L, the iodine nutrition was generally at an appropriate level. Among them, 584 pregnant women in the non-high water iodine group had a UIC of 120.9 (74.9, 191.5) μg/L, which was at the iodine deficiency level; 213 pregnant women in the high water iodine group had a UIC of 321.1 (201.9, 569.1) μg/L, which was at the iodine super-appropriate level; the differences in WIC, UIC, UIE, TII, and UI/CR between the two groups were statistically significant ( Z = 21.63, 13.34, 15.14, 15.14, 11.81, P < 0.001). After stratification by different gestational periods, the differences were statistically significant when comparing WIC and TSH in pregnant women in the non-high water iodine group and UI/CR in pregnant women in the high water iodine group by gestational period ( H = 59.13, 7.30, 13.60, P < 0.05). A total of 744 pregnant women were tested for thyroid function, and 128 cases of TSH > 2.5 mU/L, 15 cases of hypothyroxemia, and 19 cases of subclinical hypothyroidism were detected, with detection rates of 17.2%, 2.0%, and 2.6%, respectively. The differences were statistically significant when comparing TSH and TPOAb levels and the proportion of pregnant women with TSH > 2.5 mU/L in the high water iodine and non-high water iodine groups ( Z = 3.04, - 2.17, χ 2 = 6.94, P = 0.002, 0.030, 0.008). The thyroid glands of pregnant women were examined in 720 cases, and 30 cases of goiter and 150 cases of thyroid nodules were detected, with detection rates of 4.2% and 20.8%, respectively. The median thyroid volume was 8.92 ml in the high water iodine group and 8.60 ml in the non-high water iodine group, which were both within the normal range, with no statistically significant difference between the groups ( Z = - 0.75, P = 0.455). Conclusions:After changing to low iodine water, the overall iodine nutrition of pregnant women in Gaoqing County is now at an appropriate level, and the reduction of water iodine effectively reduces the risk of TSH abnormalities in local pregnant women. However, pregnant women in the non-high water iodine group are iodine deficiency, and pregnant women in the high water iodine group are at iodine super-appropriate, and the iodine nutrition level of pregnant women in this area is highly variable, which causes the "illusion" that the overall iodine level of local pregnant women is suitable.

Effects of the expression of miR-375 on the proliferation and invasion of choroidal melanoma cells / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of the expression of miR-375 on the proliferation and invasion of choroidal melanoma(CM)MUM-2B cells.METHODS: MUM-2B cells were cultured and were transfected with miR-375 mimic sequence(mimic group), miR-375 inhibitor sequence(inhibitor group), negative control group and no treatment(blank group). The qRT-PCR, CCK-8, apoptosis and Transwell experiments were used respectively to detect the expression of miR-375, cell proliferation activity, apoptosis, cell migration and invasion.RESULTS: Compared with the negative control group(1.01±0.10)and the blank group(1.03±0.07), the expression level of miR-375 in the cells of the mimic group(2.65±0.15)was increased, while the expression level of miR-375 in the cells of the inhibitor group(0.28±0.06)was decreased(P&#x003C;0.05). Compared with the blank group and negative control group, the OD values of the cells in the mimic group at 24, 48, 72, and 96h were decreased(P&#x003C;0.05), while the OD values of the cells in the inhibitor group at 24, 48, 72, and 96h were increased(P&#x003C;0.05). Compared with the apoptosis rates in the blank group and negative control group, which were(20.54±4.01)% and(22.80±4.28)%, the apoptosis rate in the mimic group(39.11±3.37)% was increased(P&#x003C;0.05), while it was decreased in the inhibitor group(10.13±2.17)%(P&#x003C;0.05). Compared with the blank group and negative control group, the number of migration cell and the number of invasion cell in the mimic group were decreased(P&#x003C;0.05), while the number of migration cell and the number of invasion cell in the inhibitor group were increased(P&#x003C;0.05). CONCLUSIONS: Up-regulating the expression of miR-375 in MUM-2B cells can reduce cell proliferation activity, accelerate cell apoptosis, and inhibit cell migration and invasion, while down-regulating the expression of miR-375 has the opposite effect. It indicates that miR-375 may play the function of tumor suppressor in the course of CM.

Enzymatic Digestion Method Coupled with Artificial Intelligence Techniques in Forensic Drowning Diatom Detection / 中山大学学报(医学科学版)

ObjectiveArtificial intelligence （AI） full smear automated diatom detection technology can perform forensic pathology drowning diatom detection more quickly and efficiently than human experts.However， this technique was only used in conjunction with the strong acid digestion method， which has a low extraction rate of diatoms. In this study， we propose to use the more efficient proteinase K tissue digestion method （hereinafter referred to as enzyme digestion method） as a diatom extraction method to investigate the generalization ability and feasibility of this technique in other diatom extraction methods. MethodsLung tissues from 6 drowned cadavers were collected for proteinase K ablation and made into smears， and the smears were digitized using the digital image matrix cutting method and a diatom and background database was established accordingly.The data set was divided into training set， validation set and test set in the ratio of 3：1：1， and the convolutional neural network （CNN） models were trained， internally validated， and externally tested on the basis of ImageNet pre-training. ResultsThe results showed that the accuracy rate of the external test of the best model was 97.65 %， and the area where the model features were extracted was the area where the diatoms were located. The best CNN model in practice had a precision of more than 80 % for diatom detection of drowned corpses. ConclusionIt is shown that the AI automated diatom detection technique based on CNN model and enzymatic digestion method in combination can efficiently identify diatoms and can be used as an auxiliary method for diatom detection in drowning identification.

Endoscopic transoral approach nasopharyngectomy for petroclival and jugular foramen nasopharyngeal carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To describe a technique of endoscopic transoral approach nasopharyngectomy for petroclival and jugular foramen nasopharyngeal carcinoma, based on anatomic studies and surgeries. Methods: Three dry human skulls and five fresh human cadaver heads were used for anatomic study of a endoscopic transoral approach to expose petroclival and jugular foramen. The anatomical landmarks and the extent of exposure were recorded. Six clinical cases who were treated in Eye & ENT Hospital, Fudan University from June 2020 to April 2022 were used to illustrate the technique and feasibility of this approach and to assess its indications and advantages, including 3 males and 3 females, aged 42 to 69 years old. Descriptive analysis was used in this research. Results: On the basis of the preservation of the internal pterygoid muscle and the external pterygoid muscle, this approach could fully expose the parapharyngeal, petrosal and paraclival segment internal carotid arteries, and safely deal with the lesions of jugular foramen and petroclival region. The 6 patients in our study tolerated the procedure well. Postoperative enhanced MRI showed complete resection of the tumor and no postoperative masticatory dysfunction. Conclusion: Endoscopic transoral approach is a safe, minimally invasive and effective surgical treatment for petroclival and jugular foramen recurrent nasopharyngeal carcinoma.

Co-occurrence trend and association study of Internet addiction and depressive symptoms among students in Inner Mongolia Autonomous Region / 中国学校卫生

Objective@#To investigate the prevalence of Internet addiction and depression of students, and to analyze the co-occurrence and trend, so as to provide a theoretical basis for prevention and controlling measures of Internet addiction and depression.@*Methods@#A total of 6 317,7 152,81 808,71 180 and 89 932 students aged 10 to 24 years from 12 leagues (103 banners) in Inner Mongolia Autonomous Region were selected by stratified random cluster sampling in September each year from 2017 to 2021. The Internet Addiction Scale and the Central for Epidemiologic Studies Depression Scale(CES-D) was used to measure Internet addiction and depression. And the annual inspection rate, group difference and annual change trend in students were calculated. Multivariate linear regression and restricted cubic spline analysis were used to estimate the linear and non linear associations between Internet addiction and depression in students.@*Results@#The Internet addiction proportion in students gradually decreased from 4.1% in 2017 to 2.1% in 2020, but increased to 3.9% in 2021. And the depressive symptoms proportion increased from 20.9% in 2017 to 28.0% in 2020 and 27.0% in 2021. The detection rate of Internet addiction and depression comorbidities remained at 1.8% to 2.5 %. The Internet addiction proportion in boys was higher than that in girls( χ 2=42.82， P <0.05). The depressive symptoms prevalence in girls was higher than that in boys( χ 2= 553.90， P <0.05). Taking reversal in prevalence of Internet addiction in urban and rural areas was observed in 2019. The detection rates of depressive symptoms and comorbidity were higher in urban areas than these in suburban counties on the whole, and the difference showed a trend of decreasing or even equalizing year by year. Internet addiction was positively correlated with depressive symptoms score ( B=1.67, 95%CI =1.64-1.71), the proportion of depressive symptoms ( OR=1.39, 95%CI =1.38-1.41) and the proportion of major depressive symptoms ( OR=1.35, 95%CI =1.33-1.36) among students in 2021 ( P <0.05). An N-shaped curve was found in the significant nonlinear associations between internet addiction and depression across sex, region and school stage.@*Conclusion@#Internet addiction and depression in students show significant linear and non-linear associations, which are consistent in different sexes, regions and school stages. Therefore, relevant measures should be made and implemented in each region, especially in suburb areas, so as to prevent the increasingly development of adolescents and children s Internet addiction and depression.

Results analysis of mNGS applied to infectious diseases / 中华预防医学杂志

The application of metagenomic second-generation sequencing (mNGS) is shifting from research to clinical laboratories due to rapid technological advances and significant cost reductions. Although many studies and case reports have confirmed that the success of mNGS in improving the prevention, diagnosis, treatment and tracking of infectious diseases, there are still some obstacles that must be overcome. The results of mNGS show all the possible pathogens in the sample, however, in the face of thousands of microbes that can infect humans, it remains challenging to accurately identify the key pathogens. So far, there is no unified interpretation standard for mNGS in clinical practice. This article reviews the interpretation of mNGS results for pathogen infection in different systems, the clinical interpretation and application regulations of mNGS results, and the challenges of mNGS interpretation in pathogen diagnosis.

Effect of procalcitonin on lipopolysaccharide-induced expression of nucleotide-binding oligomerization domain-like receptor protein 3 and caspase-1 in human umbilical vein endothelial cells / 中国当代儿科杂志

OBJECTIVES@#To study the effect of procalcitonin (PCT) on lipopolysaccharide (LPS)-induced expression of the pyroptosis-related proteins nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and caspase-1 in human umbilical vein endothelial cells (HUVECs).@*METHODS@#HUVECs were induced by LPS to establish a model of sepsis-induced inflammatory endothelial cell injury. The experiment was divided into two parts. In the first part, HUVECs were randomly divided into four groups: normal control, LPS (1 μg/mL), PCT (10 ng/mL), and LPS+PCT (n=3 each). In the second part, HUVECs were randomly grouped: normal control, LPS, and LPS+PCT of different concentrations (0.1, 1, 10, and 100 ng/mL) (n=3 each). Quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression levels of NLRP3 and caspase-1 in each group.@*RESULTS@#In the first experiment: compared with the normal control group, the PCT, LPS, and LPS+PCT groups had significantly upregulated mRNA and protein expression levels of NLRP3 and caspase-1 (P<0.05); compared with the LPS group, the LPS+PCT group had significantly downregulated mRNA and protein expression levels of NLRP3 and caspase-1 (P<0.05). In the second experiment: compared with those in the LPS group, the mRNA and protein expression levels of NLRP3 and caspase-1 in the LPS+PCT of different concentrations groups were significantly downregulated in a concentration-dependent manner (P<0.05).@*CONCLUSIONS@#LPS can promote the expression of the pyroptosis-related proteins NLRP3 and caspase-1 in HUVECs, while PCT can inhibit the LPS-induced expression of the pyroptosis-related proteins NLRP3 and caspase-1 in HUVECs in a concentration-dependent manner.

The Functional, Psychological and Economic Impacts 6 Months Post Major Trauma

Purpose@#The consequences of severe traumatic injury extend beyond hospital admission and have the potential for long-term functional, psychological, and economic sequalae. This study investigated patient outcomes 6 months following major trauma. @*Methods@#Using the National Trauma Registry, database of patients who were admitted between 2016-18 in a tertiary trauma hospital for major trauma [Injury Severity Score (ISS) ≥ 16] a review was performed on 6-month outcomes [including functional outcomes, self-reported state of health and outcome scores (EuroQol-5 Dimension score and Glasgow Outcome Scale Extended)].Result: There were 637 patients who were treated for major trauma (ISS ≥ 16); the median age was 64 years (range 16-100) and 435 (68.3%) patients were male. The most common injury mechanisms included falling from height (56.5%) and motor vehicle accident (27.0%). The median ISS was 24 (range 16-75). After 6 months, 87.6% of responders were living at home, 25.0% were back to work, and 55.1% were ambulating independently. The median self-rated state of health was 73 at baseline and 64 at 6 months. Age and length of stay were independent predictors of return to ambulation using multivariate analysis. Age, Abbreviated Injury Scale external, Glasgow Coma Scale on Emergency Department arrival, heart rate, and need for transfusion were independent predictors of failure to return to work at 6 months using multivariate analysis. Charlson Comorbidity Index, Glasgow Coma Scale on arrival, temperature, pain and need for inpatient rehabilitation were independent predictors of mortality at 6 months. @*Conclusion@#Recovery from major trauma is multi-faceted and requires a team-based approach well beyond discharge.

Relationship between depression and anxiety with sleep quality in elderly adults / 中华老年医学杂志

Objective:To evaluate the influence of depression and anxiety on sleep quality, and to provide a basis for preventing sleep disorders in community-dwelling older adults.Methods:Cluster sampling was used.A self-designed questionnaire, the Pittsburgh Sleep Quality Index(PSQI), the Patient Health Questionnaire-9(PHQ-9), and the Generalized Anxiety Disorder Questionnaire-7(GAD-7)were used for the survey.The sleep quality and the influence of depression and anxiety on sleep quality of 955 community-dwelling older adults aged 60 and above were investigated.Results:The detection rate of sleep disorders, depression and anxiety were 24.5%, 19.1% and 14.3%, respectively.There was a positive correlation between sleep quality scores(including the total score and the scores of each dimension)and the anxiety and depression scores( rs: 0.115-0.558, P<0.01 for all). After adjusting for possible confounding effects of gender, age, food intake or tea drinking before bed, Logistic regression analysis showed that the presence of depression( OR=3.555, 95% CI: 2.235-5.653, P<0.05)and anxiety( OR=1.812, 95% CI: 1.070-3.070, P<0.05)were significantly related to sleep disorders in the elderly.The multivariate adjusted population attributable risk of depression and anxiety for sleep disorders in the elderly was 32.56% and 16.09%, respectively.The presence of depression and anxiety were associated with 38.87% of the population attributable risk for sleep disorders. Conclusions:Depression and anxiety are important risk factors for sleep disorders in the elderly.Strengthening the identification and intervention of depression and anxiety is beneficial to improve the sleep quality of elderly living in the community.

Exploration of the continuing education of physicians in a primary military hospital: competency-based neurological education / 中华医学教育探索杂志

During the mandate duty in primary military hospital, we conducted continuing neurological education combining with the hospitals trait and department needs. By using the concept of competency-based education, we have explored a pattern of continuing medical education suitable for primary physicians. Thematic approach was implemented for acquiring professional knowledge, formative evaluation was applied for training effect assessment, and scientific clinical thinking was emphasized for promoting the demand of lifelong learning. Under the communication and efforts of teachers and learners, we have obtained good clinical effect and positive social affection by the competency-based neurological education.

Recent advance of procalcitonin in central nervous system diseases / 中华神经科杂志

Procalcitonin, as a biological marker of bacterial infection, has been widely used in clinical diagnosis of various infectious diseases. With the development of basic and clinical research, it has been found that procalcitonin not only plays a cascading and amplifying role in systemic inflammatory response, but also exerts an important effect on assessment, diagnosis, and prognosis in some central nervous system diseases. In this article, "procalcitonin" "bacterial meningitis""marker" and "central nervous system diseases" were used to search the relevant literatures published from 1993 to 2021 in the databases of Pubmed, Wanfang Medicine and China Knowledge Network. The roles of procalcitonin in central nervous system diseases were systemically reviewed for assisting the diagnosis and treatment of central nervous system diseases.

Abdominal puncture drainage alleviates severe acute pancreatitis in rats by activating Nrf-2/HO-1 pathway and promoting autophagy / 南方医科大学学报

OBJECTIVE@#To assess the effect of early abdominal puncture drainage (APD) on autophagy and Nrf-2/HO-1 pathway in rats with severe acute pancreatitis (SAP) and explore the possibile mechanism.@*METHODS@#Thirty-two male SD rats were randomly divided into sham-operated (SO) group, SAP group with retrograde injection of 4% sodium taurocholate, APD group with insertion of a drainage tube into the lower right abdomen after SAP induction, and APD + ZnPP group with intraperitoneal injection of 30 mg/kg ZnPP 12 h before APD modeling. Blood samples were collected from the rats 12 h after modeling for analysis of amylase and lipase levels and serum inflammatory factors. The pathological changes of the pancreatic tissue were observed with HE staining. Oxidative stress in the pancreatic tissue was detected with colorimetry, and sub-organelle structure and autophagy in pancreatic acinar cells were observed by transmission electron microscopy. The expressions of autophagy-related proteins and Nrf-2/HO-1 pathway were detected using RT-PCR and Western blotting.@*RESULTS@#Compared with those in SAP group, the rats with APD treatment showed significantly alleviated pathologies in the pancreas, reduced serum levels of lipase, amylase and inflammatory factors, lowered levels of oxidative stress, and activated expressions of Nrf-2/HO-1 pathway in the pancreas. The ameliorating effect of ADP was significantly inhibited by ZnPP treatment before modeling. APD obviously reversed mitochondrial and endoplasmic reticulum damages and p62 accumulation induced by SAP.@*CONCLUSION@#APD treatment can suppress oxidative stress and repair impaired autophagy in rats with SAP by activating the Nrf-2/HO-1 pathway, thereby reducing the severity of SAP.

Role of CaMK II in pancreatic injury in mice with severe acute pancreatitis / 南方医科大学学报

OBJECTIVE@#To investigate the expression of Ca2+/calmodulin-dependent protein kinase II (CaMK Ⅱ) in pancreatic tissues of mice with severe acute pancreatitis (SAP) and explore the protective effect of KN93, a CaMK Ⅱ inhibitor, against pancreatic injury in SAP and the possible mechanism.@*METHODS@#Thirty-six healthy male C57 mice were randomly divided into sham operation group, SAP group, KN93 group and SAP + KN93 group (n=9). Serum and pancreatic tissue samples were collected 24 h after modeling. The pathological changes in the pancreatic tissues were observed using HE staining. Serum lipase and amylase activities and the levels of inflammatory factors were detected using ELISA. Western blotting was used to detect the expressions of CaMK Ⅱ, p-CaMK Ⅱ, p-NF-κB, MAPK and p-MAPK in mouse pancreas.@*RESULTS@#Compared with those in sham operation group, the expressions of p-CaMK Ⅱ, p-NF-κB and p-MAPK were significantly increased in SAP group (P < 0.05). KN93 treatment obviously alleviated pathological injuries of the pancreas in SAP mice, and significantly lowered serum levels of lipase, amylase and inflammatory factors (TNF-α and IL-6) and phosphorylation levels of NF-κB, ERK and MAPK proteins (P < 0.05).@*CONCLUSION@#The activity of CaMK Ⅱ is significantly increased in the pancreatic tissue of SAP mice. KN93 can alleviate pancreatic injury and inflammation in SAP mice possibly through the ERK/MAPK signaling pathway.

Comparison of postoperative mid-term and long-term quality of life between Billroth-I gastroduodenostomy and Billroth-II gastrojejunostomy after radical distal gastrectomy in patients with gastric cancer: a cohort study based on a case registry database / 中华胃肠外科杂志

Objective: The pattern of digestive tract reconstruction in radical gastrectomy for gastric cancer is still inconclusive. This study aims to compare mid-term and long-term quality of life after radical gastrectomy for distal gastric cancer between Billroth-I (B-I) and Billroth-II (B-II) reconstruction. Methods: A retrospective cohort study was conducted.Clinicopathological and follow-up data of 859 gastric cancer patients were colected cellected from the surgical case registry database of Gastrointestinal Surgery Center of Sichuan University West China Hospital, who underwent radical distal gastric cancer resection between January 2016 and December 2020. Inclusion criteria: (1) gastric cancer confirmed by preoperative gastroscopy and biopsy; (2) elective radical distal major gastrectomy performed according to the Japanese Society for Gastric Cancer treatment guidelines for gastric cancer; (3) TNM staging referenced to the American Cancer Society 8th edition criteria and exclusion of patients with stage IV by postoperative pathology; (4) combined organ resection only involving the gallbladder or appendix; (5) gastrointestinal tract reconstruction modality of B-I or B-II; (6) complete clinicopathological data; (7) survivor during the last follow-up period from December 15, 2021 to January 15, 2022. Exclusion criteria: (1) poor compliance to follow-up; (2) incomplete information on questionnaire evaluation; (3) survivors with tumors; (4) concurrent malignancies in other systems; (5) concurrent psychiatric and neurological disorders that seriously affected the objectivity of the questionnaire or interfered with patient's cognition. Telephone follow-up was conducted by a single investigator from December 2021 to January 2022, and the standardized questionnaire EORTC QLQ-C30 scale (symptom domains, functional domains and general health status) and EORTC QLQ-STO22 scale (5 symptoms of dysphagia, pain, reflux, restricted eating, anxiety; 4 single items of dry mouth, taste, body image, hair loss) were applied to evaluate postoperative quality of life. In 859 patients, 271 were females and 588 were males; the median age was 57.0 (49.5, 66.0) years. The included cases were divided into the postoperative follow-up first year group (202 cases), the second year group (236 cases), the third year group (148 cases), the fourth year group (129 cases) and the fifth year group (144 cases) according to the number of years of postoperative follow-up. Each group was then divided into B-I reconstruction group and B-II reconstruction group according to procedure of digestive tract reconstruction. Except for T-stage in the fourth year group, and age, tumor T-stage and tumor TNM-stage in the fifth year group, whose differences were statistically significant between the B-I and B-II reconstruction groups (all P<0.05), the differences between the B-I and B-II reconstruction groups in terms of demographics, body mass index (BMI), tumor TNM-stage and tumor pathological grading in postoperative follow-up each year group were not statistically significant (all P>0.05), suggesting that the baseline information between B-I reconstruction group and the B-II reconstruction group in postoperative each year group was comparable. Evaluation indicators of quality of life (EORTC QLQ-C30 and EORTC QLQ-STO22 scales) and nutrition-related laboratory tests (serum hemoglobin, albumin, total protein, triglycerides) between the B-I reconstruction group and B-II reconstruction group in each year group were compared. Non-normally distributed continuous variables were presented as median (Q(1),Q(3)), and compared by using the Wilcoxon rank sum test (paired=False). The χ(2) test or Fisher's exact test was used for comparison of categorical variables between groups. Results: There were no statistically significant differences in all indexes EORTC QLQ-30 scale between the B-I reconstruction group and the B-II reconstruction group among all postoperative follow-up year groups (all P>0.05). The EORTC QLQ-STO22 scale showed that significant differences in pain and eating scores between the B-I reconstruction group and the B-II reconstruction group were found in the second year group, and significant differences in eating, body and hair loss scores between the B-I reconstruction group and the B-II reconstruction group were found in the third year group (all P<0.05), while no significant differences of other item scores between the B-I reconstruction group and the B-II reconstruction group were found in postoperative follow-up of all year groups (P>0.05). Triglyceride level was higher in the B-II reconstruction group than that in the B-I reconstruction group (W=2 060.5, P=0.038), and the proportion of patients with hyperlipidemia (triglycerides >1.85 mmol/L) was also higher in the B-II reconstruction group (19/168, 11.3%) than that in the B-I reconstruction group (0/34) (χ(2)=0.047, P=0.030) in the first year group with significant difference. Albumin level was lower in the B-II reconstruction group than that in the B-I reconstruction group (W=482.5, P=0.036), and the proportion of patients with hypoproteinemia (albumin <40 g/L) was also higher in the B-II reconstruction group (19/125, 15.2%) than that in the B-I reconstruction group (0/19) in the fifth year group, but the difference was not statistically significant (χ(2)=0.341, P=0.164). Other nutrition-related clinical laboratory tests were not statistically different between the B-I reconstruction and the B-II reconstruction in each year group (all P>0.05). Conclusions: The effects of both B-I and B-II reconstruction methods on postoperative mid-term and long-term quality of life are comparable. The choice of reconstruction method after radical resection of distal gastric cancer can be based on a combination of patients' condition, sugenos' eoperience and operational convenience.

Observation on efficacy of pterygium excision combined with autologous limbal epithelial bulbar conjunctival transplantation in the treatment of patients with pterygium / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To observe the efficacy of pterygium excision combined with autologous limbal epithelial bulbar conjunctival transplantation in the treatment of patients with pterygium. METHODS:Prospective controlled study. A total of 102 patients(102 eyes)with pterygium treated in the hospital between October 2015 and October 2019 were selected as study subjects, and they were divided into observation group and control group according to the random number table method, with 51 cases in each group. The control group was treated with pterygium excision combined with amniotic membrane transplantation, and the observation group was given pterygium excision combined with autologous limbal epithelial bulbar conjunctival transplantation. The perioperative indicators(intraoperative blood loss, surgical time, corneal epithelial repair time)and clinical efficacy at 3mo after surgery were compared between the two groups, and the disease recovery-related indicators \〖tear film break-up time(BUT), uncorrected visual acuity(UCVA), Schirmer Ⅰ test(SⅠt), corneal astigmatism degree(CAD)\〗 before and 3mo after surgery, postoperative aesthetic degree and recurrence during follow-up were recorded.RESULTS:The corneal epithelial repair time in observation group was shorter than that in control group(4.14±1.35 <i>vs</i> 4.72±1.37d,<i>P</i><0.05), while the surgical time was longer than that in control group(32.24±6.69 <i>vs</i> 29.67±5.21min,<i>P</i><0.05), and there was no statistical significance in the intraoperative blood loss between the two groups(<i>P</i>>0.05). At 3mo after surgery, there was no statistical difference in the effective rate of treatment between the two groups(86.3% <i>vs</i> 78.4%, <i>P</i>>0.05). At 3mo after surgery, the BUT, UCVA and SⅠt in the two groups were significantly enhanced compared with those before surgery(all <i>P</i><0.05), and the UCVA and SⅠt in observation group were higher than those in control group(all <i>P</i><0.05), but there was no statistical difference in the BUT between the two groups(<i>P</i>>0.05). The CAD in the two groups was significantly lower than that before surgery(<i>P</i><0.05), but the difference was not significant between the groups(<i>P</i>>0.05). At 3mo after surgery, the scores of dimensions of aesthetic scale for pterygium treatment(ocular recovery, subjective symptoms)were significantly higher in observation group than those in control group(all <i>P</i><0.05), but there were no statistical differences in the scores of cleanliness of surgical area and congestion between the two groups(all <i>P</i>>0.05). There was no statistically significant difference in recurrence rate between the two groups during follow-up(<i>P</i>>0.05).CONCLUSION: Pterygium excision combined with autologous limbal epithelial bulbar conjunctival transplantation can effectively treat pterygium and prevent recurrence, and it has faster postoperative recovery and better aesthetic degree compared to pterygium excision combined with amniotic membrane transplantation.

Network pharmacology study of flavone extracts of Silybum marianum in the treatment of nonalcoholic fatty liver disease / 药学学报

To investigate the therapeutic effect and molecular mechanism of the main flavonoid components of Silybum marianum (S. marianum) on nonalcoholic fatty liver disease (NAFLD), we identified nine flavonoids in S. marianum through TCMSP, PubChem database and corresponding literatures. The potential therapeutic targets of NAFLD were predicted by SwissTargetPrediction, GeneCards and Venny 2.1.0 platform, while the protein-protein interaction (PPI) network of potential targets was analyzed using String platform and Cytoscape software. Then GO and KEGG pathway enrichment analysis were performed using David 6.8 database, followed by molecular docking verification using AutoDock software. In vitro, components with higher degree value in the "components-targets-pathway" network were chosen for further analysis. L02 cells were used to establish lipid accumulation model and treated with different components. Furthermore, the effects of four pure active compounds from S. marianum on lipid accumulation in hepatocytes were analyzed by oil red O staining. The results showed that the main nine flavonoids extracted from S. marianum contained 24 potential NAFLD targets. Several critical pathways closely related to NAFLD process were identified by GO and KEGG enrichment analysis, including phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) pathway, type 2 diabetes pathway, tumor necrosis factor (TNF) pathway and insulin resistance pathway. The results of molecular docking further indicated that the core components displayed strong binding abilities with key targets respectively, and silandrin showed better binding activity as compared to other components. The results obtained from L02 cells showed that the lipid accumulation was reduced by treatment with isosilybin A, isosilybin B, silydianin and silychristin, while the activity of isosilybin B was better than that of isosilybin A. Taken together, we concluded that the main flavone components of S. marianum could improve lipid accumulation through multiple signaling pathway in hepatocytes, and this could be a potential new strategy for the treatment of NAFLD.

Effect of Wuzhishan Callicarpa nudiflora in Hainan Province on Cisplatin-induced Apoptosis of Nasopharyngeal Carcinoma Cells and Mechanism： Based on Nrf2/ARE Pathway / 中国实验方剂学杂志

ObjectiveTo explore the effect of Wuzhishan Callicarpa nudiflora （LHZZ） on the sensitivity of nasopharyngeal carcinoma （NPC） cells to cisplatin （DDP） and the mechanism. MethodCell counting kit-8 （CCK-8） assay was used to detect the survival rate of NPC HNE1 cells after treatment with different concentration of DDP （0，2，4，8，16，32 mg·L-1） and different concentration of LHZZ （0，25，50，75，100 mg·L-1）. The following groups were designed： control group （normal HNE1 cells），DDP group （8 mg·L-1 DDP，24 h），LHZZ group （50 mg·L-1 LHZZ，24 h），DDP + LHZZ group （8 mg·L-1 DDP + 50 mg·L-1 LHZZ，24 h），DDP + LHZZ + nuclear factor erythroid 2-related factor 2 （Nrf2） activator sulforaphane （SFN） group （8 mg·L-1 DDP + 50 mg·L-1 LHZZ，24 h， 10 μmol·L-1 SFN，24 h）. Then CCK-8 assay was employed to examine cell survival rate，colony formation test the colony-forming ability，flow cytometry and in situ terminal end-labeling（TUNEL） staining cell apoptosis，fluorescent probe 2'，7'-dichlorofluorescin diacetate （DCFH-DA） the level of reactive oxygen species （ROS） in cultured cells，Western blot the expression of apoptosis-related proteins in cells，such as B-cell lymphoma/leukemia-2 （Bcl-2），Bcl-2 associated X protein （Bax），and cysteinyl aspartate specific proteinase-3 （Caspase-3），and Real-time quantitative polymerase chain reaction （Real-time PCR） the expression of Nrf2 and antioxidant response element （ARE） mRNA in cells. ResultThe survival rates of cells treated with different concentration of DDP and different concentration of LHZZ decreased compared with that in the control group （P<0.05）. Compared with the DDP group and the LHZZ group，DDP + LHZZ group demonstrated decrease in cell survival rate，number of cell colonies，and Bcl-2 level，and increase in the apoptosis level and the expression of Bax and Caspase-3 （P<0.05）. However，after the addition of SFN，the Nrf2/ARE signaling pathway was activated and the above variation was inhibited （P<0.05）. In addition，the level of intracellular ROS in the LHZZ group was lower than that in the control group （P<0.05） and the level in the DDP + LHZZ group was lower than that in the DDP group （P<0.05）. Moreover，the ROS level in the DDP + LHZZ + SFN group was higher than that in the DDP+LHZZ group （P<0.05）. ConclusionLHZZ can enhance the sensitivity of DDP-induced NPC apoptosis，possibly by blocking the Nrf2/ARE signaling pathway and inhibiting the level of ROS.