ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

Objective:To investigate the characteristics of brain network reorganization in migraine patients and its relationship with the grading of right-to-left shunt (RLS) in patent foramen ovale(PFO) by integrated 3.0T structural magnetic resonance imaging (MRI),resting-state functional MRI(fMRI),and contrast-enhanced transthoracic echocardiography, thereby toexplore the mechanism underlying cognitive impairment in migraine.Methods:A total of 49 migraine patients (migraine group)and 16 demographically matched healthy subjects (healthy control group) who received diagnosis and treatment at China-Japan Union Hospital of Jilin University from September 2020 to September 2023 were selected as the study participants. Structural images (T1-weighted) and resting-state functional images were obtained from brain imaging (MRI and fMRI) data. The amplitude of low-frequency fluctuation (ALFF) algorithm was used to quantify the intensity of spontaneous neural activity in brain regions, while the Fazekas scale and the Age-Related White Matter Changes (ARWMC) scale were employed to assess white matter lesions. Participants were evaluated using the Mini-Mental State Examination (MMSE). Based on the results of contrast-enhanced transthoracic echocardiography (cTTE),the migraine group was further subdivided into A1 group (18 cases, no PFO), A2 group (17 cases, PFO with small-to-moderate RLS) and A3 group (14 case, PFO with large RLS) group, the differences in brain functional activity and cognitive function were compared among these groups.Results:By Fazekas scale scores and ARWMC scale scores, the incidence of hyperintense foci in the deep white matter regions in the migraine group were higher than those in the healthy control group: 67.3%(33/49) vs. 6/16, 61.2%(30/49) vs. 5/16, there were statistical differences ( P<0.05). Compared with the healthy control group, the migraine group exhibited higher spontaneous neural activity intensity in the brainstem,bilateral posterior cingulate cortex,left medial frontal gyrus,and left middle frontal gyrus,while showing reduced brain activity in the right angular gyrus region. The short-term delayed recall scores and total MMSE scores in the migraine group were lower than thosein the healthy control group: (1.61 ± 1.06) scores vs. (2.44 ± 0.81) scores, (25.06 ± 2.31) scores vs. (27.94 ± 1.44) scores, there were statistical differences ( P<0.05). The short-term delayed recall scores mong the A1 group, A2 group and A3 group had statistical difference( P<0.05). Conclusions:Migraine patients exhibit specific brain functional network reorganization and cognitive dysfunction, which are closely related to the degree of RLS.

Objective:To investigate the characteristics of brain network reorganization in migraine patients and its relationship with the grading of right-to-left shunt (RLS) in patent foramen ovale(PFO) by integrated 3.0T structural magnetic resonance imaging (MRI),resting-state functional MRI(fMRI),and contrast-enhanced transthoracic echocardiography, thereby toexplore the mechanism underlying cognitive impairment in migraine.Methods:A total of 49 migraine patients (migraine group)and 16 demographically matched healthy subjects (healthy control group) who received diagnosis and treatment at China-Japan Union Hospital of Jilin University from September 2020 to September 2023 were selected as the study participants. Structural images (T1-weighted) and resting-state functional images were obtained from brain imaging (MRI and fMRI) data. The amplitude of low-frequency fluctuation (ALFF) algorithm was used to quantify the intensity of spontaneous neural activity in brain regions, while the Fazekas scale and the Age-Related White Matter Changes (ARWMC) scale were employed to assess white matter lesions. Participants were evaluated using the Mini-Mental State Examination (MMSE). Based on the results of contrast-enhanced transthoracic echocardiography (cTTE),the migraine group was further subdivided into A1 group (18 cases, no PFO), A2 group (17 cases, PFO with small-to-moderate RLS) and A3 group (14 case, PFO with large RLS) group, the differences in brain functional activity and cognitive function were compared among these groups.Results:By Fazekas scale scores and ARWMC scale scores, the incidence of hyperintense foci in the deep white matter regions in the migraine group were higher than those in the healthy control group: 67.3%(33/49) vs. 6/16, 61.2%(30/49) vs. 5/16, there were statistical differences ( P<0.05). Compared with the healthy control group, the migraine group exhibited higher spontaneous neural activity intensity in the brainstem,bilateral posterior cingulate cortex,left medial frontal gyrus,and left middle frontal gyrus,while showing reduced brain activity in the right angular gyrus region. The short-term delayed recall scores and total MMSE scores in the migraine group were lower than thosein the healthy control group: (1.61 ± 1.06) scores vs. (2.44 ± 0.81) scores, (25.06 ± 2.31) scores vs. (27.94 ± 1.44) scores, there were statistical differences ( P<0.05). The short-term delayed recall scores mong the A1 group, A2 group and A3 group had statistical difference( P<0.05). Conclusions:Migraine patients exhibit specific brain functional network reorganization and cognitive dysfunction, which are closely related to the degree of RLS.

Microplastics(MPs)have attracted growing attention worldwide as an increasingly prevalent environmental pollutant.In addition,chicken meat is currently the most widely consumed kind of poultry in the global market.Consumer demand for chicken is on the rise both at home and abroad.As a result,the safety of chicken raising has also received significant attention.The lungs play an essential role in the physiological activities of chickens,and they are also the most vulnerable organs.Lung injury is difficult to repair after the accumulation of contaminants,and the mortality rate is high,which brings huge economic losses to farmers.The research on the toxicity of MPs has mainly focused on the marine ecosystem,while the mechanisms of toxicity and lung damage in chickens have been poorly studied.Thus,this study explored the effects of exposure to polystyrene microplastics(PS-MPs)at various concentrations for 42 d on chicken lungs.PS-MPs could cause lung pathologies and ultrastructural abnormalities,such as endoplasmic reticulum(ER)swelling,inflammatory cell infiltration,chromatin agglutination,and plasma membrane rupture.Simultaneously,PS-MPs increased the expression of genes related to the heat shock protein family(Hsp60,Hsp70,and Hsp90),ER stress signaling(activating transcription factor 6(ATF6),ATF4,protein kinase RNA-like ER kinase(PERK),and eukaryotic translation initiation factor 2 subunit α(eIF2α)),pyroptosis-related genes(NOD-,LRR-and pyrin domain-containing protein 3(NLRP3),apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),interleukin-1β(IL-1β),cysteinyl aspartate-specific proteinase 1(Caspase1),and gasdermin-D(GSDMD)),and the inflammatory signaling pathway(nuclear factor-κB(NF-κB),inducible nitric oxide synthase(iNOS),and cyclooxygenase-2(COX-2)).The above results showed that PS-MP exposure could result in lung stress,ER stress,pyroptosis,and inflammation in broilers.Our findings provide new scientific clues for further research on the mechanisms of physical health and toxicology regarding MPs.

Microplastics(MPs)and nanoplastics(NPs)have become hazardous materials due to the massive amount of plastic waste and disposable masks,but their specific health effects remain uncertain.In this study,fluorescence-labeled polystyrene NPs(PS-NPs)were injected into the circulatory systems of mice to determine the distribution and potential toxic effects of NPs in vivo.Interestingly,whole-body imaging found that PS-NPs accumulated in the testes of mice.Therefore,the toxic effects of PS-NPs on the reproduction systems and the spermatocytes cell line of male mice,and their mechanisms,were investigated.After oral exposure to PS-NPs,their spermatogenesis was affected and the spermatogenic cells were damaged.The spermatocyte cell line GC-2 was exposed to PS-NPs and analyzed using RNA sequencing(RNA-seq)to determine the toxic mechanisms;a ferroptosis pathway was found after PS-NP exposure.The phenomena and indicators of ferroptosis were then determined and verified by ferroptosis inhibitor ferrostatin-1(Fer-1),and it was also found that nuclear factor erythroid 2-related factor 2(Nrf2)played an important role in spermatogenic cell ferroptosis induced by PS-NPs.Finally,it was confirmed in vivo that this mechanism of Nrf2 played a protective role in PS-NPs-induced male reproductive toxicity.This study demonstrated that PS-NPs induce male reproductive dysfunction in mice by causing spermatogenic cell ferroptosis dependent on Nrf2.

As an important reproductive organ in women, ovary plays a vital role in maintaining reproductive health and quality of life. Ovarian aging refers to the decline of ovarian function and eventually failure, which not only leads to the decline of female fertility, but also accelerates female aging and causes a series of related diseases, which seriously threatens female reproductive health and quality of life. Therefore, elucidating the mechanism of ovarian aging and further exploring the anti-aging strategies of the ovary are of great significance for slowing down ovarian aging and maintaining female fertility. This article reviews and analyzes the relevant studies of ovarian aging at home and abroad, summarizes the relevant mechanisms of ovarian aging and puts forward the corresponding prevention and treatment strategies.

As an important reproductive organ in women, ovary plays a vital role in maintaining reproductive health and quality of life. Ovarian aging refers to the decline of ovarian function and eventually failure, which not only leads to the decline of female fertility, but also accelerates female aging and causes a series of related diseases, which seriously threatens female reproductive health and quality of life. Therefore, elucidating the mechanism of ovarian aging and further exploring the anti-aging strategies of the ovary are of great significance for slowing down ovarian aging and maintaining female fertility. This article reviews and analyzes the relevant studies of ovarian aging at home and abroad, summarizes the relevant mechanisms of ovarian aging and puts forward the corresponding prevention and treatment strategies.

Objective:To explore the efficacy of the combination of radiofrequency ablation(RFA) and endoscopic metal stent in the treatment of patients with unresectable cholangiocarcinoma.Methods:From January 3, 2012 to June 30, 2019, at the Department of Endoscopic of the Third Affiliated Hospital of Naval Medical University, the clinical data of 44 patients with unresectable cholangiocarcinoma who were treated by the combination of RFA and endoscopic metal stent were retrospectively collected, which included age, gender, location of cholangiocarcinoma(hilar cholangiocarcinoma and distal cholangiocarcinoma), etc. Postoperative evaluation was conducted based on the follow-up, including clinical success rate, postoperative complication rate, time of stent patency and overall survival time (OS). The Kaplan-Meier method and log-rank test were used to analyze the difference of OS between patients with hilar cholangiocarcinoma and distal cholangiocarcinoma. Mann-Whitney U test was used for statistical analysis. Results:The age of the 44 patients with cholangiocarcinoma was (70.3±11.6) years old, with 20 males (45.5%). There were 22 patients (50.0%) with hilar cholangiocarcinoma and 22 patients (50.0%) with distal cholangiocarcinoma. The clinical success rate of 44 patients was 93.2%(41/44). A total of 5 patients(11.4%) had postoperative complications, which were all improved by appropriate treatment. The median time of follow-up of the 44 patient was 9.2 months(ranged from 3.1 to 57.6 months), the median time of stent patency was 7.0 months (ranged from 5.8 to 8.2 months). Thirty-two patients (72.7%) died during the follow-up, and the median OS was 10.9 months(ranged from 9.0 to 12.8 months). The median OS of patients with hilar cholangiocarcinoma was 7.8 months(ranged from 4.6 to 11.0 months) and that of patients with distal cholangiocarcinoma was 12.5 months(ranged from 5.7 to 19.4 months), and there was no statistically significant difference( P>0.05). Conclusion:RFA combined with endoscopic metal stent is safe and effective in the treatment of patients with unresectable cholangiocarcinoma.

Objective:To explore the long-term effect of endoscopic radiofrequency ablation for the treatment of unresectable ampullary carcinoma.Methods:Clinical data of patients with ampullary carcinoma who received endoscopic radiofrequency ablation in the Third Affiliated Hospital of Naval Medical University from January 2012 to May 2019 were retrospectively collected, including basic information, frequency of radiofrequency ablation, the type of biliary stent, postoperative complications, and follow-up. Kaplan-Meier method was used to analyze the survival of patients after endoscopic radiofrequency ablation. Relationship between frequency of radiofrequency ablation, type of biliary stent and overall survival time was analyzed.Results:A total of 50 patients were enrolled, including 31 males and 19 females, aged 73.0±9.7 years. Twenty-five patients (50.0%) underwent 1 radiofrequency ablation treatment, while 25 patients (50.0%) underwent radiofrequency ablation treatments more than twice. Postoperative complications occurred in 6 patients (12.0%), all of which were mild symptoms. The average follow-up was 22.3 months, with a total of 39 (78.0%) deaths, 5 (10.0%) lost to follow-up, and 6 (12.0%) surviving. The median overall survival time was 16.9 (95% CI: 9.1-24.8) months, with cumulative survival rates of 62.0%, 38.5%, 27.0%, and 12.6% at 1, 2, 3, and 5 years, respectively. The median overall survival time of those treated with radiofrequency ablation ≥2 times showed a trend of prolongation compared to patients treated once, but the difference was not statistically significant [26.7 (95% CI: 9.7-43.7) months VS 12.6 (95% CI: 4.9-20.3) months, χ2=3.049, P=0.081]. Plastic stents were used in 32 patients (64.0%) and metal stents in 18 patients (36.0%). There was no significant difference in median overall survival time between patients using metal and plastic stents [17.1 (95% CI: 6.1-28.0) months VS 15.9 (95% CI: 6.9-24.9) months， χ2=0.029， P=0.865]. Conclusion:Endoscopic radiofrequency ablation is a safe treatment for unresectable ampullary carcinoma, and multiple consecutive treatments may increase the survival benefit.

Objective:To investigate the efficacy of endoscopic stent placement for patients with Bismuth type Ⅳ hilar cholangiocarcinoma.Methods:Data of 229 patients with unresectable Bismuth type Ⅳ hilar cholangiocarcinoma who successfully underwent endoscopic stent placement at the Department of Endoscopy, the Third Affiliated Hospital of Naval Medical University from January 2002 to January 2019 were retrospectively analyzed. Outcomes included clinical success rate, complication incidence, stent patency period and overall survival time. The patency of stents and overall survival time of patients were estimated by using the Kaplan-Meier method. The independent predictors for stent patency and overall survival of patients were analyzed by a multivariate Cox proportional regression model.Results:The overall clinical success rate was 78.2% (179/229). The incidence of early cholangitis after endoscopic retrograde cholangiopancreatography was 20.5% (47/229). The median stent patency and overall survival time were 5.7 (95% CI: 4.8-6.7) months and 5.1 (95% CI: 4.2-6.0) months, respectively. Further multivariate Cox regression analysis showed that metal stent ( P<0.001, HR=0.452, 95% CI: 0.307-0.666) and bilateral stents with bilateral angiography ( P=0.036, HR=0.644, 95% CI: 0.427-0.971) were independent predictors of stent patency; total bilirubin>200 μmol/L ( P=0.001, HR=1.627, 95% CI: 1.208-2.192), metal stent ( P=0.004, HR=0.636, 95% CI: 0.467-0.866) and antitumor therapy ( P<0.001, HR=0.439, 95% CI:0.308-0.626) were independent predictors of overall survival. Conclusion:There is high incidence of cholangitis in patients with unresectable Bismuth type Ⅳ hilar cholangiocarcinoma treated with endoscopic stenting. Longer stent patency can be achieved with metal stent placement and bilateral drainage. In addition, metal stent for drainage and antitumor therapy can also help increase the survival benefit.