[Emphasizing the timing and procedure selection for vitrectomy in pathological myopic traction maculopathy].

Myopic maculopathy is the primary cause of irreversible visual impairment in patients with pathologic myopia, and myopic traction maculopathy often requires vitrectomy for treatment. Myopic traction maculopathy encompasses epiretinal membrane, foveoschisis, macular hole, and macular hole-related retinal detachment. It is recommended to perform vitrectomy combined with inner limiting membrane peeling for Type II epiretinal membrane, foveal-sparing inner limiting membrane peeling for foveoschisis, inverted inner limiting membrane flap technique for macular hole, and vitrectomy combined with macular buckle for refractory macular hole-related retinal detachment. Myopic traction maculopathy is a chronically progressive condition, and surgeons need to accurately determine the timing of surgery and choose appropriate procedures to maximize the benefits for patients.

[Preliminary study on automatic quantification and grading of leopard spots fundus based on deep learning technology].

Objective: To achieve automatic segmentation, quantification, and grading of different regions of leopard spots fundus (FT) using deep learning technology. The analysis includes exploring the correlation between novel quantitative indicators, leopard spot fundus grades, and various systemic and ocular parameters. Methods: This was a cross-sectional study. The data were sourced from the Beijing Eye Study, a population-based longitudinal study. In 2001, a group of individuals aged 40 and above were surveyed in five urban communities in Haidian District and three rural communities in Daxing District of Beijing. A follow-up was conducted in 2011. This study included individuals aged 50 and above who participated in the second 5-year follow-up in 2011, considering only the data from the right eye. Color fundus images centered on the macula of the right eye were input into the leopard spot segmentation model and macular detection network. Using the macular center as the origin, with inner circle diameters of 1 mm, 3 mm, and outer circle diameter of 6 mm, fine segmentation of the fundus was achieved. This allowed the calculation of the leopard spot density (FTD) and leopard spot grade for each region. Further analyses of the differences in ocular and systemic parameters among different regions' FTD and leopard spot grades were conducted. The participants were categorized into three refractive types based on equivalent spherical power (SE): myopia (SE<-0.25 D), emmetropia (-0.25 D≤SE≤0.25 D), and hyperopia (SE>0.25 D). Based on axial length, the participants were divided into groups with axial length<24 mm, 24-26 mm, and>26 mm for the analysis of different types of FTD. Statistical analyses were performed using one-way analysis of variance, Kruskal-Wallis test, Bonferroni test, and Spearman correlation analysis. Results: The study included 3 369 participants (3 369 eyes) with an average age of (63.9±10.6) years; among them, 1 886 were female (56.0%) and 1, 483 were male (64.0%). The overall FTD for all eyes was 0.060 (0.016, 0.163); inner circle FTD was 0.000 (0.000, 0.025); middle circle FTD was 0.030 (0.000, 0.130); outer circle FTD was 0.055 (0.009, 0.171). The results of the univariate analysis indicated that FTD in various regions was correlated with axial length (overall: r=0.38, P<0.001; inner circle: r=0.31, P<0.001; middle circle: r=0.36, P<0.001; outer circle: r=0.39, P<0.001), subfoveal choroidal thickness (SFCT) (overall: r=-0.69, P<0.001; inner circle: r=-0.57, P<0.001; middle circle: r=-0.68, P<0.001; outer circle: r=-0.72, P<0.001), age (overall: r=0.34, P<0.001; inner circle: r=0.30, P<0.001; middle circle: r=0.31, P<0.001; outer circle: r=0.35, P<0.001), gender (overall: r=-0.11, P<0.001; inner circle: r=-0.04, P<0.001; middle circle: r=-0.07, P<0.001; outer circle: r=-0.11, P<0.001), SE (overall: r=-0.20; P<0.001; inner circle: r=-0.19, P<0.001; middle circle: r=-0.20, P<0.001; outer circle: r=-0.20, P<0.001), uncorrected visual acuity (overall: r=-0.18, P<0.001; inner circle: r=-0.26, P<0.001; middle circle: r=-0.24, P<0.001; outer circle: r=-0.22, P<0.001), and body mass index (BMI) (overall: r=-0.11, P<0.001; inner circle: r=-0.13, P<0.001; middle circle: r=-0.14, P<0.001; outer circle: r=-0.13, P<0.001). Further multivariate analysis results indicated that different region FTD was correlated with axial length (overall: ß=0.020, P<0.001; inner circle: ß=-0.022, P<0.001; middle circle: ß=0.027, P<0.001; outer circle: ß=0.022, P<0.001), SFCT (overall: ß=-0.001, P<0.001; inner circle: ß=-0.001, P<0.001; middle circle: ß=-0.001, P<0.001; outer circle: ß=-0.001, P<0.001), and age (overall: ß=0.002, P<0.001; inner circle: ß=0.001, P<0.001; middle circle: ß=0.002, P<0.001; outer circle: ß=0.002, P<0.001). The distribution of overall (H=56.76, P<0.001), inner circle (H=72.22, P<0.001), middle circle (H=75.83, P<0.001), and outer circle (H=70.34, P<0.001) FTD differed significantly among different refractive types. The distribution of overall (H=373.15, P<0.001), inner circle (H=367.67, P<0.001), middle circle (H=389.14, P<0.001), and outer circle (H=386.89, P<0.001) FTD differed significantly among different axial length groups. Furthermore, comparing various levels of FTD with systemic and ocular parameters, significant differences were found in axial length (F=142.85, P<0.001) and SFCT (F=530.46, P<0.001). Conclusions: The use of deep learning technology enables automatic segmentation and quantification of different regions of theFT, as well as preliminary grading. Different region FTD is significantly correlated with axial length, SFCT, and age. Individuals with older age, myopia, and longer axial length tend to have higher FTD and more advanced FT grades.

[Analysis of clinical characteristics of 129 acute and chronic occupational brucellosis in HulunBuir City].

Objective: To analyze the epidemiological characteristics and clinical data of acute and chronic occupational brucellosis patients in order to provide a scientific basis for the prevention and treatment of occupational brucellosis. Methods: In October 2022, a study was conducted on 129 patients diagnosed with occupational brucellosis by HulunBuir Center for Disease Control and Prevention from January 2016 to December 2021. The epidemiological characteristics, clinical features, and laboratory test results of patients in the acute and chronic phases were compared and analyzed using chi-square test and student's t test. Results: The acute phase patients included 38 men and 4 women with an average age of (36.6±8.4) years old; the chronic phase patients included 73 men and 14 women with an average age of (38.4±7.9) years old. There were no significant differences in gender and age between the two groups (P>0.05). The patients had a clear history of occupational exposure, and the proportion of veterinarians in acute stage (21 cases, 50.0%) was significantly higher than that in chronic stage (25 cases, 28.7%), the difference was statistically significant (P<0.05). The symptoms of fever and loss of appetite in acute phase of occupational brucellosis were significantly higher than those in chronic phase, and the symptoms of fatigue and joint muscle pain were significantly lower than those in chronic phase, with statistical significances (P<0.05). The increase of alanine aminotransferase, aspartate aminotransferase, C-reactive protein, erythrocyte sedimentation rate and positive rate of blood culture in acute stage were significantly higher than those in chronic stage, with statistical significances (P<0.05) . Conclusion: Occupational brucellosis patients are predominantly middle-aged men, the acute phase is characterized by fever, loss of appetite, and increased inflammatory indicators and liver enzymes, while the chronic phase is characterized by symptoms such as fatigue and joint muscle pain. Brucellosis related occupational exposure population should seek medical treatment as soon as possible when the above symptoms occur, timely detection and treatment of occupational diseases.

[Pancreaticoduodenectomy combined with longitudinal pancreaticojejunostomy in the treatment of chronic pancreatitis: initial experience in 11 cases].

Objective: To investigate the surgical strategy for chronic pancreatitis complicated with suspected malignant lesions in the pancreatic head and pancreatolithiasis in the distal pancreas. Methods: This is a retrospective cohort study. Clinical data from 11 patients with chronic pancreatitis who underwent pancreaticoduodenectomy combined with longitudinal pancreaticojejunostomy(PD-L) were retrospectively collected(PD-L group) from the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi'an Jiaotong University between December 2021 and September 2023. All patients were male with an age of (49.0±11.2) years(range:32 to 70 years). Their primary preoperative diagnoses included pancreatic lesions, chronic pancreatitis, pancreatolithiasis, and dilatation of the pancreatic duct. Data from 248 patients who underwent pancreaticoduodenectomy(PD) during the same period were retrospectively collected(PD group). There were 157 males and 91 females in the PD group, with an age of (61.5±10.8) years(range:27 to 82 years). Among them, 87 cases were diagnosed as pancreatic cancer or chronic pancreatitis. The propensity score matching method was used to reduce confounding bias between the two groups. The caliper value of 0.1 was used and the 1∶4 nearest neighbor matching method was used for the matching. Comparisons between the two groups were made using the independent sample t test, Mann-Whitney U test or χ2 test,respectively. Results: After complete excision of the specimen during pancreaticoduodenectomy, the key surgical step of PD-L was longitudinal pancreaticojejunostomy in the remaining pancreas. Intraoperative blood loss in the PD-L group was lower than that in the PD group [M(IQR)](300(200)ml vs. 500(500)ml, respectively; P<0.05). Similarly, hospitalization days(21.0(7.0)days vs. 25.0(8.5)days) and postoperative hospitalization days(13.0(8.0)days vs. 17.0(5.0) days) were also lower in the PD-L group compared to the PD group (P<0.05). There were no significant differences in the operation time and postoperative complication rate between the two groups(P>0.05). In the PD-L group, the postoperative follow-up time was 5(5)months(range: 3 to 21 months). One case was lost for follow-up. Abdominal pain was relieved in 10 patients. Additionally, abdominal distension and steatosis were alleviated in 8 cases. Furthermore, 5 cases of diabetes mellitus showed improved control of HbA1c and fasting blood glucose levels after surgery. Conclusions: PD-L treatment can be used to treat chronic pancreatitis complicated by suspected malignant lesions in the pancreatic head and pancreatolithiasis in the distal pancreas. PD-L also has advantages in removing stones from the pancreatic duct and evaporation of pancreatic fluid. However, due to the single-center design and the small sample size of this study, further practice and long-term follow-up are still necessary.

[Cancer incidence and mortality in China, 2022].

Objective: The National Central Cancer Registry estimates the number of new cancer cases and deaths in China in 2022, using incidence and mortality data collected by the National Cancer Center. Methods: According to the data of 700 cancer registries in 2018 and the data of 106 cancer registries from 2010 to 2018, the age-period-cohort model was used to estimate the incidence rate and mortality rate of all cancers and 23 types of cancer in 2022, stratified by gender and urban and rural areas. We estimated the number of new cancer cases and deaths in China in 2022 based on the estimated rate and population data in 2022. Results: The estimated results showed that in 2022, there were approximately 4 824 700 new cancer cases in China (2 533 900 in males and 2 290 800 in females), with an age-standardized incidence rate of Chinese population (ASIR) of 208.58 per 100 000 (212.67 per 100 000 for males and 208.08 per 100 000 for females). Approximately 2 903 900 new cancer cases occurred in urban areas, with an ASIR of 212.95 per 100 000. It was estimated about 1 920 800 new cancer cases in rural areas, and the ASIR was 199.65 per 100 000. The top five cancers (lung cancer 1 060 600, colorectal cancer 517 100, thyroid cancer 466 100, liver cancer 367 700 and female breast cancer 357 200) accounted for 57.4% of all new cases. The estimated number of deaths from cancer in China in 2022 was 2 574 200 (1 629 300 in males and 944 900 in females), with an age-standardized mortality rate of Chinese population (ASMR) of 97.08 per 100 000 (127.70 per 100 000 in males and 68.67 per 100 000 in females). The number of deaths from cancer in urban and rural areas was about 1 400 600 and 1 173 400, with the ASMR of 92.37 and 103.97 per 100 000 in urban and rural areas, respectively. The top five leading cause of cancers death (lung cancer 733 300, liver cancer 316 500, gastric cancer 260 400, colorectal cancer 240 000 and esophageal cancer 187 500) accounted for 67.5% of all cancer deaths. Lung cancer ranked first in the incidence and mortality in men and women. The incidence rate in urban areas was higher than that in rural areas, while the mortality rate was lower than that in rural areas. Conclusions: The burden of cancer in China is still relatively heavy, with significant differences in cancer patterns in gender, urban-rural, and regional. The burden of cancer presents a coexistence of developed and developing countries, and the situation of cancer prevention and control is still serious in China.

[Research progress and prospects of artificial intelligence in diagnosis and treatment of colorectal cancer].

Colorectal cancer is one of the most common malignant tumors worldwide. Due to the heterogeneity in patient outcomes and treatment responses to standard therapy regimens, personalized diagnostic and therapeutic strategies have remained a focus of sustained interest in research. In recent years, with the rapid progression of artificial intelligence (AI) technology in the medical field, an abundance of phased research results has emerged in the decision-making for preoperative, intraoperative, and postoperative diagnostic and therapeutic plans for colorectal cancer, demonstrating great potential for application. This new and efficient solution provides for the personalized evaluations and auxiliary diagnoses and treatments of patients with colorectal cancer. In the future, AI systems may continue to advance towards multimodal, multi-omics, and real-time directions. This paper aims to explore the current state of research on the multi-faceted auxiliary applications of AI in the diagnosis and treatment of colorectal cancer, as well as to present a prospective view of the innovations that AI technology could bring to personalized colorectal cancer treatment in the future and the challenges it may face.

The environmental and socioeconomic effects of tuberculosis patients in the southwest of China: a population-based study.

OBJECTIVE: The objective of this study was to assess the incidence of tuberculosis (TB) and find the risk factors of TB patients with a high burden of TB in socioeconomic level, the high level of TB incidence and the great changes of economic and social factors, explore the possible factors, construct scientific and robust prediction model, and analyse whether the task of stopping TB can be accomplished by the expected global deadline. STUDY DESIGN: This was an ecological study. METHODS: Descriptive analysis, spatial and space-time scan, correlation analysis, and regression analysis were carried out, based on cases of TB in Sichuan Province and ecological data from 2006 to 2017, to explore the characters of TB and ecological factors, using the transfer function-noise model to forecast the trend of TB until 2035. RESULTS: Factors affecting the incidence of TB, increasing per capita green area, reporting status of TB among Tibetans and Yi minorities, comprehensive treatment management, total cost of TB per capita for urban residents, proportion of males with high school education, 20 to 20 h of 24-h accumulated precipitation, reducing HIV at the same time as AIDS deaths, the increase in the proportion of males in junior high school education, and the increase in the number of registered TB cases can reduce the incidence of TB. CONCLUSIONS: There was concentration mainly on enhanced control of the environment and society measures, helpful in guiding government planning to control TB. Reinforcement is required to reduce the TB of population aged 15-24 and aged 25-64 in socioeconomic level by 2035.

[A case of disseminated nocardiosis in a non-immunosuppressed host].

Nocardia is an opportunistic pathogen that most commonly affects immunosuppressed hosts, while disseminated infections in healthy hosts are rare. In this paper, we described a case of disseminated Nocardia infection in a non-immunosuppressed host whose initial imaging was strikingly similar to systemic metastasis from a tumor. Since no tumor cells were found in any of the numerous biopsies taken, we considered infection by specific pathogens before metagenomic next-generation sequencing of a lumbar spine tissue biopsy finally confirmed the diagnosis of Nocardia infection. To help doctors better understand this condition and avoid misdiagnosis a, this article provided a summary of the clinical characteristics, diagnostic techniques, and therapeutic options for disseminated nocardiosis.

Chronically high stress hormone levels dysregulate sperm long noncoding RNAs and their embryonic microinjection alters development and affective behaviours.

Previous studies on paternal epigenetic inheritance have shown that sperm RNAs play a role in this type of inheritance. The microinjection of sperm small noncoding RNAs into fertilised mouse oocytes induces reprogramming of the early embryo, which is thought to be responsible for the differences observed in adult phenotype. While sperm long noncoding RNAs (lncRNAs) have also been investigated in a previous study, their microinjection into fertilised oocytes did not yield conclusive results regarding their role in modulating brain development and adult behavioural phenotypes. Therefore, in the current study we sought to investigate this further. We used our previously established paternal corticosterone (stress hormone) model to assess sperm lncRNA expression using CaptureSeq, a sequencing technique that is more sensitive than the ones used in other studies in the field. Paternal corticosterone exposure led to dysregulation of sperm long noncoding RNA expression, which encompassed lncRNAs, circular RNAs and transposable element transcripts. Although they have limited functional annotation, bioinformatic approaches indicated the potential of these lncRNAs in regulating brain development and function. We then separated and isolated the sperm lncRNAs and performed microinjections into fertilised oocytes, to generate embryos with modulated lncRNA populations. We observed that the resulting adult offspring had lower body weight and altered anxiety and affective behavioural responses, demonstrating roles for lncRNAs in modulating development and brain function. This study provides novel insights into the roles of lncRNAs in epigenetic inheritance, including impacts on brain development and behaviours of relevance to affective disorders.

[High expression of secretogranin II increases oxaliplatin resistance of colorectal cancer cells].

OBJECTIVE: To investigate the expression of secretogranin II (SCG2) in colorectal cancer (CRC) tissues and its impact on oxaliplatin resistance of CRC cells. METHODS: We performed immunohistochemistry to detect the expression level of SCG2 on a tissue microarray containing 96 CRC and 84 adjacent tissues and analyzed the association of SCG2 expression with the clinical features of the CRC patients. SCG2 expression was also measured in DLD1 cells treated with oxaliplatin using immunoblotting and RT-qPCR analyses. The effects of SCG2 expression on oxaliplatin sensitivity and cell viability were evaluated in a DLD1 cell model of SCG2 knockout established using CRISPR-cas9 technique, and the expressions of apoptosis-related proteins were detected using Western blotting and RT-qPCR. We further examined SCG2 expression levels in an oxaliplatin-resistant DLD1 cell line and its parental DLD1 cells. RESULTS: SCG2 expression was significantly increased in CRC tissues as compared with the adjacent tissues (1.932±0.816 vs 1), and the tumor tissues in advanced stages showed higher SCG2 expression levels. In DLD1 cells, treatment with oxaliplatin significantly increased SCG2 expression, and SCG2 knockout obviously increased oxaliplatin sensitivity of the cells and enhanced the expressions of apoptosis-related proteins. Compared with the parental cells, oxaliplatin-resistant DLD1 cells showed a significant increase of SCG2 expression by 3.901±0.471 folds. CONCLUSION: SCG2 may serve as a risk gene in CRC, and its high expression increases oxaliplatin resistance of CRC cells.

[Construction of Tianjin occupational disease prevention and control ability assessment system based on Delphi method].

Objective: To establish a systematic, scientific, reasonable, feasible and reliable evaluation system for occupational disease prevention and control capability, in order to provide reference for occupational disease prevention and control work in Tianjin City. Methods: In August 2022, literature review was conducted to propose indicators for the evaluation system. Two rounds of anonymous consultation with occupational health experts were conducted using the Delphi method to form expert opinions. According to the boundary value method and expert opinions, eliminate, screen, and modify the evaluation system indicators to ultimately determine the system indicators. Use Cronbach's alpha to test the reliability of the system indicators and form a Tianjin occupational disease prevention and control capability evaluation system. Results: It showed that the effective response rates of the two rounds of consultation conducted by experts in this study were 92.3% and 100.0%, respectively. The expert authority coefficients were 0.84 and 0.82, respectively. The Kendall coordination coefficient was tested for differences, and the differences were statistically significant (P<0.05). The Tianjin occupational disease prevention and control capability evaluation system includes 7 primary indicators, 17 secondary indicators, and 54 tertiary indicators. The Cronbach's alpha of the primary, second, third level indicators and all indicators were 0.91, 0.98, 0.98, 0.98 (>0.7) . Conclusion: The preliminary evaluation system for occupational disease prevention and control capacity in Tianjin City has been established, providing a reference basis for the investigation of occupational disease prevention and control capacity in Tianjin City.

[Short term clinical observation of keratoconus treated with stromal lenticule addition keratoplasty combined with corneal collagen cross-linking].

Objective: To investigate the efficacy of Femtosecond laser-assisted stromal lenticule addition keratoplasty (SLAK) combined with corneal collagen cross-linking (CXL) in the treatment of middle and advanced Keratoconus. Methods: It was a retrospective case series study. Data of 23 cases (24 eyes) of keratoconus treated with femtosecond laser-assisted SLAK combined with CXL in Laser Vision Centre of Xi'an No.1 Hospital from September 2020 to June 2022 were collected, including 16 males and 7 females, aged (23.69±5.18) years. The thickness, diopter number and diameter of the donor corneal stromal lens were assessed. uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), and diopter were recorded before and 1, 3, and 6 months after surgery. Sirius 3D fault corneal topography instrument to measure flat simulated keratometry (Kf), steep simulated keratometry (Ks) and the difference between them (ΔK), as well as central corneal thickness (CCT) and corneal high-order aberration. Results: Six months after surgery, CCT (454.83±50.01) µm were significantly higher than before (384.92±35.45) µm (P<0.05). Six months after surgery, UCVA (1.41±0.32) was significantly lower than before (1.11±0.33)(P<0.05). Six months after surgery, spherical diopter [(-15.73±7.89) D], Kf [(56.82±4.76) D] and Ks [(61.00±4.70) D] were significantly higher than before [(-12.08±5.99) D, (53.55±4.95) D, (58.65±5.10) D] (P<0.05). There was no significant difference in BCVA, column mirror degree and higher order aberrations before and 6 months after surgery(P>0.05). No corneal stromal lens folds, melting and displacement were observed in all eyes during the follow-up period, and no corneal opacity or immune rejection was observed. Conclusions: femtosecond laser-assisted SLAK combined with CXL can significantly increase the corneal thickness of keratoconus and has good effectiveness. In addition, six months of postoperative follow-up of patients showed no significant changes in BCVA and high-order aberrations in the 6 mm central diameter of the cornea, and no postoperative adverse reaction were found in all eyes, indicating that the operation has certain safety.

miR-146a aggravates cognitive impairment and Alzheimer disease-like pathology by triggering oxidative stress through MAPK signaling.

INTRODUCTION: Mir-146a-5p has been widely recognized as a critical regulatory element in the immune response. However, recent studies have shown that miR-146a-5p may also be involved in the development of Alzheimer disease (AD). Regrettably, the related mechanisms are poorly understood. Here, we investigated the effects of miR-146a in mice models and SH-SY5Y cells treated with amyloid ß (Aß)1-42. METHODS: To create a model of AD, SH-SY5Y cells were treated with Aß1-42 and mice received intracerebroventricular injections of Aß1-42. Then, the transcriptional levels of miR-146a were estimated by real-time PCR. We transiently transfected the miR-146a-5p mimic/inhibitor into cells and mice to study the role of miR-146a. The role of signaling pathways including p38 and reactive oxygen species (ROS) was studied by using specific inhibitors. Aß and amyloid-beta precursor protein (APP)levels were measured by immunoblotting. Furthermore, Aß expression was analyzed by immunofluorescence and histochemical examinations. RESULTS: Aß1-42-stimulated SH-SY5Y cells displayed increased transcriptional levels of miR-146a and APP. Moreover, the p38 MAPK signaling pathway and ROS production were activated upon stimulation with a miR-146a-5p mimic. However, treatment with a miR-146a-5p inhibitor decreased the levels of APP, ROS, and p-p38 MAPK. A similar phenomenon was also observed in the animals treated with Aß1-42, in which miR-146a upregulation increased the expression of Aß, p-p38, and ROS, while the inhibition of miR-146a had the opposite effect. This suggests that miR-146a increases Aß deposition and ROS accumulation via the p-p38 signaling pathway. CONCLUSIONS: Our research demonstrates that miR-146a-5pa increases Aß deposition by triggering oxidative stress through activation of MAPK signaling.

miR-146a aggravates cognitive impairment and Alzheimer disease-like pathology by triggering oxidative stress through MAPK signalingmi / R-146a empeora el deterioro cognitivo y la patología tipo Alzheimer al promover el estrés oxidativo a través de la vía de señalización MAPK

Introduction: Mir-146a-5p has been widely recognized as a critical regulatory element in the immune response. However, recent studies have shown that miR-146a-5p may also be involved in the development of Alzheimer disease (AD). Regrettably, the related mechanisms are poorly understood. Here, we investigated the effects of miR-146a in mice models and SH-SY5Y cells treated with amyloid β (Aβ)1–42. Methods: To create a model of AD, SH-SY5Y cells were treated with Aβ1–42 and mice received intracerebroventricular injections of Aβ1–42. Then, the transcriptional levels of miR-146a were estimated by real-time PCR. We transiently transfected the miR-146a-5p mimic/inhibitor into cells and mice to study the role of miR-146a. The role of signaling pathways including p38 and reactive oxygen species (ROS) was studied by using specific inhibitors. Aβ and amyloid-beta precursor protein (APP)levels were measured by immunoblotting. Furthermore, Aβ expression was analyzed by immunofluorescence and histochemical examinations. Results: Aβ1–42-stimulated SH-SY5Y cells displayed increased transcriptional levels of miR-146a and APP. Moreover, the p38 MAPK signaling pathway and ROS production were activated upon stimulation with a miR-146a-5p mimic. However, treatment with a miR-146a-5p inhibitor decreased the levels of APP, ROS, and p-p38 MAPK. A similar phenomenon was also observed in the animals treated with Aβ1–42, in which miR-146a upregulation increased the expression of Aβ, p-p38, and ROS, while the inhibition of miR-146a had the opposite effect. This suggests that miR-146a increases Aβ deposition and ROS accumulation via the p-p38 signaling pathway. Conclusions: Our research demonstrates that miR-146a-5pa increases Aβ deposition by triggering oxidative stress through activation of MAPK signaling.(AU)

Introducción: miR-146a-5p es un elemento regulador clave en la respuesta inmune. Sin embargo, estudios recientes sugieren que miR-146a-5p también está involucrado en el desarrollo de la enfermedad de Alzheimer (EA), aunque aún no se conoce con exactitud el mecanismo por el que esto sucede. Analizamos los efectos de miR-146a en un modelo animal y en células SH-SY5Y expuestas a β-amiloide (Aβ)1-42. Métodos: Tratamos células SH-SY5Y con Aβ1-42 e inyectamos Aβ1-42 en los ventrículos cerebrales de ratones para generar un modelo celular y otro animal de EA. Estimamos los niveles transcripcionales de miR-146a mediante PCR en tiempo real. Al mismo tiempo, transfectamos temporalmente las células y los ratones con imitador/inhibidor de miR-146a-5p para evaluar el papel de miR-146a. Estudiamos el papel de algunas vías de señalización, como la de p38, y los niveles de especies reactivas de oxígeno (ERO) con inhibidores específicos. Los niveles de Aβ y de proteína precursora amiloidea (APP) se determinaron con inmunoblot. También se analizó la expresión de Aβ mediante inmunofluorescencia y análisis histoquímico. Resultados: Las células SH-SY5Y expuestas a Aβ1-42 mostraron altos niveles transcripcionales de miR-146a y APP. La vía de señalización p-38 MAPK y la producción de EROs se activaron al utilizar un imitador de miR-146a-5p. Sin embargo, el bloqueo de miR-146a-5p con un inhibidor redujo los niveles de APP, EROs y p-p38 MAPK. Se observó un fenómeno similar en los ratones tratados con Aβ1-42: la sobrerregulación de miR-146a aumentó la expresión de Aβ, p-p38 y EROs, mientras que la inhibición de miR-146a tuvo el efecto contrario. Esto sugiere que miR-146a está involucrado en el aumento de acumulación de Aβ y de producción de EROs por medio de la vía de señalización p-p38. Conclusiones: Nuestro estudio muestra que miR146a-5p aumenta la acumulación de Aβ al promover el estrés oxidativo a través de la activación de la vía de señalización MAPK.(AU)

[Membrane anatomy-based splenic hilar lymph node dissection for gastric cancer].

There is a consensus that selectively perform splenic lymph node dissection is necessary for high-risk patients with proximal gastric cancer to achieve radical treatment. However, there are still some outstanding issues that need to be solved during the practice of splenic lymph node dissection. These include poorly defined boundaries, technical difficulties, and blurred boundaries in No. 10 and No. 11 lymph nodes, etc. Membrane anatomy has achieved successful applications in the field of gastric and colorectal surgery in recent years. The study of membrane anatomy in the splenic hilum region is controversial due to the special location of the splenic hilum, which involves multiple organs and affiliated mesentery undergoing complex rotation, folding, and fusion during embryonic development. In this manuscript, we summarize the following points based on existing research and personal experience regarding membrane anatomy. 1. There is a membrane anatomical structure that can be used for lymph node dissection in the splenic hilum region. 2. The membrane structure in the splenic hilum region can be divided into two layers: the superficial layer is composed of the dorsal mesogastrium, and the deep layer is composed of Gerota fascia, the tail of the pancreas, and the mesentery of the transverse colon (from head to tail). 3. There is a loose space between the two layers that can be used for separation during surgery. The resection of the dorsal mesogastrium belongs to D2 dissection. The No. 10 lymph node in the deeper layer belongs to the duodenal mesentery, and the resection of the No.10 lymph node exceeds D2 dissection. The complete excision of the gastric dorsal mesentery is consistent with the D2+CME surgical mode proposed by Gong Jianping's group.

[Application of novel non-endoscopic device in the screening and early diagnosis of esophageal cancer].

Esophageal cancer (EC) is a dreadful disease with a poor prognosis and poses heavy health burden worldwide. Developing effective methods to identify high-risk individuals is urgently needed for preliminary screening before endoscopy. The novel non-endoscopic device has the potential advantages of low cost, simple operation, and minimal invasiveness. Approximately 90% of participants can swallow the device successfully with high safety profiles, and sufficient esophageal exfoliated cells can be collected for cytological examination and biomarker detection. Cytological examination based on the device combined with trefoil factor 3 (TFF3) protein or DNA methylation examinations could effectively screen Barrett's esophagus-associated dysplasia and early esophageal adenocarcinoma, but large prospective studies are needed to further validate the diagnostic value of this device to improve the quality of evidence. Although the device-based cytological examination in combination with biomarker detection holds promise in the early screening of esophageal squamous dysplasia and early esophageal squamous cell carcinoma, related research is still in its infancy, and there is still a lack of sufficient evidence for population screening in China. Active research into the application of this novel non-endoscopic device in EC screening and early diagnosis is of great significance for optimizing EC screening strategies and improving the early diagnosis of EC.

[Efficacy and safety evaluation of immunotherapy combined with targeted therapy as second-line treatment in patients with metastatic non-clear cell renal cell carcinoma].

Objective: This study aimed to evaluate the efficacy and safety of programmed death-1 (PD-1) inhibitor combined tyrosine kinase inhibitor (TKI) therapy versus TKI monotherapy as the second-line regimen for patients with metastatic non-clear cell renal carcinoma (nccRCC) who failed first-line TKI therapy. Methods: The clinicopathological data of 67 patients with metastatic nccRCC who failed first-line TKI therapy between October 2011 and September 2020 were retrospectively analyzed, including 22 patients who received TKI monotherapy and 45 patients who received TKI plus PD-1 inhibitor as the second-line therapy. The efficacy was assessed according to Response Evaluation Criteria in Solid Tumors version 1.0/1.1 (RECIST 1.0/1.1), the Kaplan-Meier method was used to plot the survival curves, and the Log rank test was used to analyze the differences in the survival between the two groups. Treatment-related adverse events (AEs) after treatment were observed in both groups. Results: The overall objective response rate (ORR) and disease control rate (DCR) were 37.3% (25/67) and 56.7% (38/67), respectively. The overall second-line progression-free survival (PFS) was 7.7 months and Overall Survival (OS) was 25.2 months. The ORR and DCR of patients in the combination therapy group were 48.9% (22/45) and 71.1% (32/45), respectively, which were significantly improved compared with the TKI monotherapy group [13.6% (3/22) and 27.3% (6/22), respectively] (P=0.007 and P=0.001, respectively). The median PFS of 9.2 months for second-line treatment was longer in patients in the combination therapy group than in the TKI monotherapy group (5.2 months, P=0.001), but the median OS was not statistically different between the two groups (28.2 months vs 20.8 months, P=0.068). Common treatment-related AEs included hypertension, diarrhea, fatigue, stomatitis, hand-foot syndrome, and hypothyroidism. The incidence of hypothyroidism was higher in the combination therapy group [40.0% (18/45)] than in the TKI monotherapy group [22.7% (5/22), P=0.044]; the incidence of other treatment-related AEs between the two groups were not statistically significant (all P>0.05). Conclusion: Immune-targeted combination therapy was more effective than TKI monotherapy alone and was well tolerated in the treatment of metastatic nccRCC patients who failed first-line TKIs.

Clinical efficacy of modified sacral fixation under Leonardo da Vinci robot laparoscopy for pelvic organ prolapse.

OBJECTIVE: The aim of this study was to analyze the clinical efficacy of modified sacral fixation under Leonardo da Vinci robot laparoscopy for pelvic organ prolapse (POP). PATIENTS AND METHODS: Sixty POP patients admitted to our hospital from January 2020 to December 2021 were picked and divided into Group A (laparoscopic Y-mesh, n = 20), Group B (laparoscopic sacrovaginal fixation, n = 20), and Group C (da Vinci robotic sacral fixation, n = 20). These three groups were compared in terms of the perioperative indexes, such as operation time, intraoperative blood loss, postoperative indwelling catheter days, anal exhaust time, postoperative hospitalization days, etc. The occurrence of short-term and long-term complications in the three groups was compared. The changes of the following index values in the POP quantification system (POP -Q) staging before and 1 year after surgery were recorded and compared among the three groups. It mainly includes the midline of the anterior vaginal wall at 3 cm from the hymenal margin (Aa), the farthest point of the anterior vaginal vault from point Aa (Ba), the farthest point of the ectocervix (C), the location of the posterior vaginal vault or rectal uterine trap (D), the midline of the posterior vaginal wall at 3 cm from the hymenal margin (Ap), and the reflection of the posterior vaginal vault at the farthest point from the Ap point (Bp) values. The changes in Pelvic Floor Distress Inventory-Short Form 20 (PFDI-20) and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) were recorded and compared before and 1 year after the operation. RESULTS: The patients in Group C had significantly lower intraoperative bleeding, postoperative indwelling catheter days, anal exhaust time, and postoperative hospitalization days compared with those in Group A and Group B (p < 0.05). There existed no statistical difference in the incidence of short-term and long-term complications between Group B and Group C (p > 0.05), but both were much lower than Group A (p < 0.05). The differences in POP-Q staging, PFDI-20 scale, and PISQ-12 scale were not statistically significant among the three groups before surgery (p > 0.05), and the POP-Q staging Aa, Ba, C, D, Ap, and Bp values, PFDI-20 scale, and PISQ-12 scale were strongly improved in three groups after the surgery (p < 0.05). However, the POP-Q staging, PFDI-20 scale, and PISQ-12 scale among the three groups had no obvious difference after the surgery (p > 0.05). CONCLUSIONS: The efficacy of modified sacral fixation under Leonardo da Vinci robot laparoscopy for POP was comparable to that of laparoscopic Y-mesh treatment and laparoscopic sacral vaginal fixation. However, da Vinci's robotic sacral fixation had the advantages of less intraoperative bleeding and faster postoperative recovery, which helped patients recover quickly and improved their quality of life.

[Analysis of the correlation between peripapillary retinal nerve fiber layer cross-sectional area and myopia in individuals aged 50 years and above].

Objective: To measure the peripapillary retinal nerve fiber layer (RNFL) cross-sectional area in individuals aged 50 years and above with different refractive errors, and analyze its correlation with axial length and refractive error. Methods: This was a cross-sectional study conducted as part of the "Beijing Eye Study". The study was population-based and longitudinally designed. In 2001, a cohort of individuals aged 40 years and above from five urban communities in Haidian District and three rural communities in Daxing District, Beijing, were surveyed. Follow-up examinations were conducted in 2011. In this study, the follow-up data from 2011 were collected and analyzed. One eye of each participant was randomly selected, and the participants were categorized into four groups based on their spherical equivalent: emmetropia group (-0.50 D≤spherical equivalent≤0.50 D), low myopia group (-3.00 D≤spherical equivalent<-0.50 D), moderate myopia group (-6.00 D≤spherical equivalent<-3.00 D), and high myopia group (spherical equivalent<-6.00 D). Spectral-domain optical coherence tomography (OCT) was used to perform circular scans with a diameter of 12° centered on the optic disc. ImageJ software and Heidelberg Eye Explorer software were used to calculate the RNFL cross-sectional area. One-way analysis of variance was used to compare the differences in RNFL thickness and RNFL cross-sectional area among different groups. Linear regression analysis was performed to analyze the correlation between RNFL thickness and axial length and spherical equivalent, as well as the correlation between RNFL cross-sectional area and axial length and spherical equivalent. Results: A total of 184 participants (184 eyes) were included in the study, including 88 males and 96 females. The median age was 59 (54, 66) years, with 87 right eyes and 97 left eyes. There were 50 participants (50 eyes) in the emmetropia group, low myopia group, and moderate myopia group, and 34 participants (34 eyes) in the high myopia group. There were no significant differences in age, gender, and eye laterality among the groups (all P>0.05). The RNFL cross-sectional areas in the emmetropia, low myopia, moderate myopia, and high myopia groups were (1.115±0.106), (1.122±0.136), (1.105±0.105), and (1.096±0.106) mm2, respectively, with no significant differences observed (F=0.43, P=0.730). The RNFL thickness in the emmetropia, low myopia, moderate myopia, and high myopia groups were (102.5±9.5), (102.5±12.1), (94.2±8.3), and (90.2±8.9) µm, respectively, with a significant difference observed (F=16.42, P<0.001). Univariate linear regression analysis was performed with spherical equivalent as the independent variable and peripapillary RNFL thickness as the dependent variable, yielding the regression equation: peripapillary RNFL thickness=102.651+1.634 × spherical equivalent (R2=0.21, P<0.001). Similarly, when axial length was used as the independent variable and peripapillary RNFL thickness as the dependent variable, the regression equation was: peripapillary RNFL thickness=174.161-3.147 × axial length (R2=0.18, P<0.001). There was no significant correlation between RNFL cross-sectional area and spherical equivalent (P=0.065) or axial length (P=0.846). Conclusions: There were no significant differences in peripapillary RNFL cross-sectional area among individuals aged 50 years and above with different axial lengths or refractive errors.