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.

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.

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.

Objective:To evaluate the feasibility, efficacy, and safety of ultra-fine metal stents for malignant hilar biliary strictures (MHBS).Methods:Ultra-fine metal stents were simultaneously placed into the intrahepatic duct of 30 patients with unresectable malignant hilar biliary strictures of Bismuth type Ⅱ or higher (based on imaging or histological and/or cytological findings) by using the stent-by-stent mode from January 2014 to June 2021 at the Department of Gastroenterology, Eastern Hepatobiliary Surgical Hospital. The technical success rate, clinical efficacy and incidence of complications were observed.Results:The technical success rate was 100.0% (30/30), and the clinical success was achieved in 28 patients (93.3%) . The mean procedure time was 55.7±20.7 min and the placement time was 28.3±18.2 min. Early adverse events included mild acute pancreatitis ( n=2) and cholangitis ( n=5). The median stent patency and the median overall survival were 243 days (95% CI: 186.6-299.4 days) and 237 days (95% CI: 149.0- 325.0 days), respectively. The incidence of late cholangitis was 36.7% (11/30). Stent malfunction occurred in 14 of the 30 patients, and 5 of them received endoscopic reintervention. The technical success rate for the reintervention was 4/5 with the mean procedure time of 49.8±6.9 min. Conclusion:Malignant hilar biliary obstruction endoscopic palliation with ultra-fine metal stents using the stent-by-stent mode is safe, feasible and effective.

The brain pericyte is a unique and indispensable part of the blood-brain barrier (BBB), and contributes to several pathological processes in traumatic brain injury (TBI). However, the cellular and molecular mechanisms by which pericytes are regulated in the damaged brain are largely unknown. Here, we show that the formation of neutrophil extracellular traps (NETs) induces the appearance of CD11b⁺ pericytes after TBI. These CD11b⁺ pericyte subsets are characterized by increased permeability and pro-inflammatory profiles compared to CD11b^- pericytes. Moreover, histones from NETs by Dectin-1 facilitate CD11b induction in brain pericytes in PKC-c-Jun dependent manner, resulting in neuroinflammation and BBB dysfunction after TBI. These data indicate that neutrophil-NET-pericyte and histone-Dectin-1-CD11b are possible mechanisms for the activation and dysfunction of pericytes. Targeting NETs formation and Dectin-1 are promising means of treating TBI.
Blood-Brain Barrier/metabolism* ; Brain/pathology* ; Brain Injuries, Traumatic/metabolism* ; Extracellular Traps/metabolism* ; Histones ; Humans ; Lectins, C-Type ; Pericytes/pathology*

Objective:To evaluate endoscopic ultrasonography (EUS) in the diagnosis and preoperative assessment of hilar cholangiocarcinoma.Methods:Data of consecutive patients with hilar biliary strictures who underwent EUS and were confirmed by postoperative pathology from April 2016 to December 2019 were collected in the retrospective study. The clinical information, EUS image characteristics and lymph nodes of patients were recorded and analyzed.Results:A total of 58 patients were finally included in our study. Hilar cholangiocarcinoma of EUS image was characterized by heterogeneous hypoechoic, non-rich blood supply masses and (or) asymmetric thickening of bile duct wall. Among the 58 cases, 45 cases (77.6%) were manifested as masses and 32 cases (55.2%) were presented as thickening of bile duct wall. Nineteen cases (32.8%) had both manifestations above. There were 10 cases of vascular invasion detected by EUS scanning, including 3 cases of portal vein invasion, 4 cases of hepatic artery invasion, 3 cases of invasion of both loci. Postoperative pathology confirmed 14 cases of vascular invasion, with the diagnostic coincidence rate of 71.4% (10/14). A total of 101 lymph nodes were found in 53 patients by EUS scanning. The malignant lymph nodes presented hypoechoic, round or oval shape, and homogeneous echo. Compared with benign lymph nodes, malignant lymph nodes had higher morphological score (11.41±0.6 VS 9.01 ± 0.15, P<0.001), but there was no significant difference in size (13.29±0.90 mm VS 11.87±0.56 mm, P=0.28). According to the malignancy criteria of EUS lymph nodes (morphological score≥12), the accuracy, the sensitivity, the specificity, the positive predictive value and the negative predictive value of EUS for malignant lymph nodes were 92.1%(93/101), 76.5% (13/17), 95.2% (80/84), 76.5% (13/17) and 95.2% (80/84) , respectively. Conclusion:EUS can show the whole extrahepatic bile duct and part of intrahepatic bile duct, which is helpful to determine the location of tumor in the diagnosis of hilar cholangiocarcinoma. Moreover, EUS is helpful to diagnose hilar cholangiocarcinoma, which is of guiding significance in operative decisions.

Objective To explore the effect of ankle pump on wound healing of diabetic foot ulcer (DFU). Methods Using convenience sampling method, patients hospitalized in Podiatry Department of Tianjin Medical University Metabolic Diseases Hospital from July to December 2015 and eligible for inclusion-exclusion criteria were recruited to control group, and patients who were hospitalized from May to October 2016 were recruited to observation group according inclusion-exclusion criteria. A total of 162 patients with DFU were recruited and 156 patients completed the whole study, with 72 cases in observation group and 84 cases in control group. Routine treatment and nursing care of DFU were given to both groups, and on the basis of that ankle pump motion therapy training was given to the observation group. After treatment for 9 weeks, the foot ulcer area, healing condition, transcutaneous arterial oxygen tension (TcPO2), foot skin temperature and ankle brachial index (ABI) were compared. In addition, the adverse events throughout the process of the two groups were recorded. Results After 9-week treatment, the healing rate of observation group was higher than the control group, and the difference wasn't statistically significant (χ2=3.714, P=0.054). The area of foot ulcer of both groups decreased, and the difference wasn't statistically significant before and after treatment (P<0.01). Ulcer surface area in the intervention group decreased more significantly after treatment than the control group(P<0.01). Wagner grading Ⅲ, Ⅳ patients' TcPO2, skin temperature of both groups,and wagner grading Ⅲ patients' ABI of oberservation group all increased than before treatment, with statistical difference (P> 0.05). There was no statistical difference of TcPO2, ABI and skin temperature between the two groups before treatment (P> 0.05). In observation group, Wagner grading Ⅱ patients' skin temperature and ABI, Wagner grading Ⅲ patients' TcPO2 and skin temperature, Wagner grading Ⅳ patients' TcPO2were all higher than those of the control group, with statistical difference (P<0.01). There were 4 cases of asymptomatic hypoglycemia in each group, and there was no statistical difference of adverse event in both groups. Conclusions The ankle pump motion has a positive effect on the wound healing of DFU, which has the advantage of high safety.