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 compare the benefits and drawbacks of primary patch expansion versus pericardial tube right ventricular-pulmonary artery connection in patients diagnosed with pulmonary atresia with ventricular septal defect (PA/VSD). Methods A retrospective study was conducted on patients diagnosed with PA/VSD who underwent primary right ventricular-pulmonary artery connection surgery at our center between 2010 and 2020. Patients were categorized into two groups based on the type of right ventricular-pulmonary artery connection: a pericardial tube group and a patch expansion group. Clinical data and imaging findings were compared between the two groups. Results A total of 51 patients were included in the study, comprising 31 males and 20 females, with a median age of 12.57 (4.57, 49.67) months. The pericardial tube group included 19 patients with a median age of 17.17 (7.33, 49.67) months, while the patch expansion group consisted of 32 patients with a median age of 8.58 (3.57, 52.72) months. In both groups, the diameter of pulmonary artery, McGoon index, and Nakata index significantly increased after treatment (P<0.001). However, the pericardial tube group exhibited a longer extracorporeal circulation time (P<0.001). The reoperation rate was notably high, with 74.51% of patients requiring further surgical intervention, including 26 (81.25%) patients in the patch expansion group and 12 (63.16%) patients in the pericardial tube group. No statistical differences were observed in long-term cure rates or mortality between the two groups (P＞0.005). Conclusion In patients with PA/VSD, both patch expansion and pericardial tube right ventricular-pulmonary artery connection serve as effective initial palliative treatment strategies that promote pulmonary vessel development and provide a favorable foundation for subsequent radical operations. However, compared to the pericardial tube approach, the patch expansion technique is simpler to perform and preserves some intrinsic potential for pulmonary artery development, making it the preferred procedure.

Objective To evaluate the pharmacokinetics characteristics of single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects.Methods This was a single-center,randomized,double-blind,placebo-controlled study.Twelve healthy adult Chinese subjects were randomized to receive single-dose of Etripamil nasal spray 70 mg(n=10)or placebo nasal spray(n=2).Blood and urine samples were collected prior and post dose.Etripamil in plasma and urine were analyzed by liquid chromatography-tandem mass spectrometry.The pharmacokinetic parameters were calculated by WinNonlin non-compartmental model.Results Following the single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects,the peak concentration of Etripamil in plasma was quickly attained,with a Cmax of(66.76±56.61)ng·mL-1 and a median(range)tmax of 4.00(3.00-5.00)min.The plasma concentrations of Etripamil had fallen approximately 65％from peak value at 25 min after dosing,and close to 80％within 50 min.The AUC0-last and AUC0-∞ were(3 104.16±2 654.46)and(4 048.77±2 682.38)ng·min·mL-1,respectively.The urine excretion percentage of Etripamil during 24 h was(0.01±0.01)％.Among the 12 subjects who were treated with Etripamil or placebo,10 subjects reported a total of 29 treatment-emergent adverse events(TEAEs).All of the TEAEs were mild in severity.The most common TEAEs were rhinorrhoea and lacrimation increased.Conclusion Etripamil was quickly absorbed after intranasal administration,followed by rapid distribution and elimination(not primarily excreted by renal);Etripamil 70 mg was safe and well tolerated by the healthy Chinese adult subjects.

Objective To evaluate early outcomes of transthoracic pulmonary valve implantation for the treatment of moderate and severe pulmonary regurgitation by using homemade self-expanding valve (SalusTM). Methods Patients with severe pulmonary regurgitation who underwent transthoracic pulmonary valve implantation in Guangdong Provincial People’s Hospital from September 2, 2021 to November 25, 2022 were prospectively enrolled. The early postoperative complications and improvement of valve and heart function were summarized and analyzed. Results A total of 25 patients were enrolled, including 16 males and 9 females, with an average age of 24.5±1.5 years and an average weight of 57.0±3.0 kg. The mean systolic diameters of the bifurcation near the main pulmonary artery, the stenosis of the middle segment of the aorta and near the valve of the right ventricular outflow tract of the patients were 31.8±7.4 mm, 30.6±5.9 mm and 38.4±8.0 mm, respectively. All patients were successfully implanted with valves, and there were no serious complications such as death, coronary compression, stent fracture, valve displacement and infective endocarditis in the early postoperative period. The indexed left atrial longitudinal diameter, indexed right atrial longitudinal diameter, and indexed right ventricular outflow tract anteroposterior diameter decreased significantly after the operation. The degree of tricuspid and pulmonary valve regurgitation and the indexed regurgitation area decreased significantly. The above differences were statistically significant (P<0.05). Conclusion The early outcomes of transthoracic pulmonary valve implantation with homemade self-expanding pulmonary valve (SalusTM) in the treatment of severe pulmonary regurgitation is relatively good, and the long-term outcomes need to be verified by the long-term follow-up studies with large samples.

Objective To analyze and summarize the early and medium-term outcomes of self-expanding interventional pulmonary valve stent (SalusTM) for right ventricular outflow tract dysfunction with severe pulmonary valve regurgitation. Methods We established strict enrollment and follow-up criteria. Patients who received interventional pulmonary valve in transthoracic implantation in Guangdong Provincial People’s Hospital from September 2, 2021 to July 18, 2023 were prospectively included, and all clinical data of patients were collected and analyzed. Results A total of 38 patients with severe pulmonary regurgitation were included, with 23 (60.5%) males and 15 (39.5%) females. The mean age was 24.08±8.12 years, and the mean weight was 57.66±13.54 kg. The preoperative mean right ventricular end-diastolic volume index (RVEDVI) and right ventricular end-systolic volume index (RVESVI) were 151.83±42.84 mL/m2 and 83.34±33.05 mL/m2, respectively. All patients successfully underwent transcatheter self-expandable pulmonary valve implantation, with 3 (7.9%) patients experiencing valve stent displacement during the procedure. Perioperative complications included 1 (2.6%) patient of postoperative inferior wall myocardial infarction and 1 (2.6%) patient of poor wound healing. The median follow-up time was 12.00 (6.00, 17.50) months. During the follow-up period, there were no deaths or reinterventions, and no patients had recurrent severe pulmonary regurgitation. Three (7.9%) patients experienced chest tightness and chest pain, and 1 (2.6%) patient developed frequent ventricular premature beats. Compared with preoperative values, the right atrial diameter, right ventricular diameter, and tricuspid annular plane systolic excursion were significantly reduced at 6 months and 1 year postoperatively, with improvement in the degree of pulmonary regurgitation (P<0.01). Compared with preoperative values, RVEDVI and RVESVI decreased to 109.51±17.13 mL/m2 and 55.88±15.66 mL/m2, respectively, at 1 year postoperatively (P<0.01). Conclusion 　Self-expanding interventional pulmonary valve in transthoracic implantation is safe and effective for severe pulmonary valve regurgitation and shows good clinical and hemodynamic results in one-year outcome.

Intracellular overexpression of cytoglobin (Cygb) has been shown to reduce extracellular matrix deposition and promote liver fibrosis recovery, but its mechanism is not yet clear. This study constructed and expressed a fusion protein (TAT-Cygb) of cell penetrating peptide TAT and Cygb, to investigate the effect of fusion protein TAT-Cygb on regulating hepatic stellate cells (HSCs) ferroptosis. Cultured human hepatic stellate cells line (LX2) were treated with TAT-Cygb and erastin in vitro, respectively. The effects of ferroptosis phenotype in LX2 cells induced by TAT-Cygb, including cell viability, cell morphology, iron ion (Fe²⁺) content, lipid peroxidation product levels, and antioxidant system indicators, were investigated using trypan blue staining, transmission electron microscopy, Prussian blue staining, and reagent kits detection. After co-treatment with TAT-Cygb and ferrostain-1, the levels of Fe²⁺, reactive oxygen species (ROS), malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) were measured by reagent kits. The protein expression levels of alpha smooth actin (α-SMA), collagen I and fibronectin were detected by Western blot, and the protein expression level of epidermal growth factor receptor (EGFR) and desmin relevant to fibrosis were observed by immunofluorescence. The results showed that TAT-Cygb could significantly reduce the viability of LX2 cells and trigger events relevant to ferroptosis, including promoting intracellular Fe²⁺ accumulation, and inducing mitochondrial morphological changes, and intensifying lipid peroxidation products accumulation, and decreasing the level of antioxidant indexes, which played a similar role as erastin; Fer-1 significantly weakened the increase in Fe²⁺, ROS, MDA, 4-HNE levels induced by TAT-Cygb, as well as the decrease in NADPH and GSH levels, while also weakening the TAT-Cygb-induced over-expression levels of α-SMA, collagen I and fibronectin, and TAT-Cygb-induced under-expression levels of EGFR and desmin. This cellular level study indicated that TAT-Cygb can induce ferroptosis of activated HSCs. This study revealed the potential mechanism of TAT-Cygb anti-liver fibrosis, and provided the experimental basis for further research on the molecular mechanism of TAT-Cygb realizing biological function by regulating the ferroptosis pathway.

Objective To evaluate the molluscicidal effect and cost of spraying molluscicides with drones against Oncomelania hupensis snails in marshland and lake areas, so as to provide new insights into field snail control in China. Methods A marshland and lake setting measuring approximately 12 000 m² was selected in Wanzhi District, Wuhu City on June 2023 as the test field, and assigned to four groups, of 3 000 m² in each group. Environmental cleaning was not conducted in groups A or B, which were given 5% niclosamide ethanolamine salt granules sprayed with knapsack-type sprayers and drones at a dose of 40 g/m², and environmental cleaning was conducted in groups C and D, which were given 5% niclosamide ethanolamine salt granules sprayed with drones and knapsack-type sprayers at a dose of 40 g/m², respectively. O. hupensis snails were surveyed before chemical treatment and 1, 3, 5, 7, 14 days post-treatment. The uniformity of chemicals was determined on the day of treatment, and the snail mortality, corrected snail mortality and density of living snails were calculated and compared among groups. The cost of molluscicides, labor fees of environmental cleaning and chemical treatment and cost of equipment were calculated, and the cost for a 1% reduction in the mean density of living snails was calculated 14 days post-treatment. Results The mean densities of living snails and mortality rates of snails were 1.82 to 2.85 snails/0.1 m² and 1.41% to 2.94% in groups A, B, C and D before chemical treatment, and the mortality and corrected mortality of snails were 55.75%, 49.32%, 85.94% and 87.50%, and 55.00%, 48.47%, 85.70% and 87.29% in groups A, B, C and D 14 days post-treatment. There was a significant difference in the mortality of snails among the four groups 14 days post-treatment (χ² = 38.735, P < 0.005), and there was a higher snail mortality in Group D than in Group A (χ² = 16.876, P < 0.005), and higher in Group C than in Group B (χ² = 20.508, P < 0.005). The density of living snails reduced by 55.00%, 43.94%, 90.43% and 87.14% 14 days post-treatment relative to pre-treatment in groups A, B, C and D, respectively. The test for uniformity of chemicals showed that the mean dose of molluscicides were 57.34, 55.21, 40.19 g/m² and 32.37 g/m² in groups A, B, C and D, respectively, and the minimal standard deviation (7.07) and coefficient of variation (0.18) of mean doses were seen in Group C. The costs for chemical treatment were 0.33 Yuan in groups A and B and 1.53 Yuan in groups C and D, respectively. The costs for a 1% reduction in the mean density of living snails were 17.82, 22.47, 50.73 Yuan and 52.56 Yuan in groups A, B, C, and D 14 days post-treatment, respectively. Conclusions The molluscicidal effect and cost of spraying 5% niclosamide ethanolamine salt granules with drones are comparable to manual spraying, and chemical treatment with drones are high in uniformity of molluscicides, time- and labor-saving, and feasible for applications in complex environments, which deserves widespread applications in the field of snail control.

Objective To investigate whether Liuwei Dihuang Pills enhances the antigen cross-presenting ability of dendritic cell(DC)by increasing gap junctional intercellular communication(GJIC),and to explore the mechanisms involved.Methods Western Blot and immunofluorescence were used to observe the effects of Liuwei Dihuang Pills-containing serum on the expression and membrane localisation of gap junction protein connexin43(Cx43)in mouse melanoma cells(B16);Calcein-AM/DiI fluorescence tracer assay was used to observe the effects of Liuwei Dihuang Pills-containing serum on the function of GJIC in B16 cells;flow cytometry was used to observe the role of GJIC in the enhancement of DC antigen presenting ability by Liuwei Dihuang Pills-containing serum;and propidium iodide(PI)/Hoechst staining assay was used to observe the immunocidal effect of CD8+ T-lymphocytes.Results Western Blot and immunofluorescence experiments showed that Liuwei Dihuang Pills-containing serum led to the up-regulation of Cx43 expression;fluorescence tracer experiments proved that the GJIC function of B16 cells was significantly enhanced by Liuwei Dihuang Pills-containing serum;flow cytometry analyses showed that the DC antigen-presenting ability was enhanced by Liuwei Dihuang Pills-containing serum;and the results of PI/Hoechst staining showed that the immuno-killing effect of CD8+T-cells was more significant after the intervention of Liuwei Dihuang Pills-containing serum in B16-OVA.Conclusion Liuwei Dihuang Pills improve the GJIC function by up-regulating the Cx43 expression of melanoma cells,and then enhance the cross-presenting ability of DCs thus activating stronger CD8+ T-cell immunocidal responses.

Objective To investigate the effect of rats'injuries and its mechanism caused by specific dose of radiation combined with decompression exposure.Methods 81 male SD rats were randomly divided into control group(n=9),radiation group(n=18),radiation+low-load decompression group(n=18),radiation+medium-load decompression group(n=18),and radiation+high-load decompression group(n=18).In addition to control group,the rats were irradiated with 60Co γ rays at 4 Gy and then underwent rapid escape experiments.The high-pressure exposure schemes were to stay underwater 57 m for 30 min,45 min or 60 min and reduce to normal pressure within(30±5)s,respectively.The high-pressure exposure was not carried out in radiation group.The behavior and death of rats in each group were observed 0.5 h after leaving the cabin.Blood(abdominal aorta)and lung tissues were collected at 3 h and 72 h,respectively.The changes of lung wet-dry weight ratio(W/D),lung pathology and serum levels of interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α),superoxide dismutase(SOD),malondialdehyde(MDA),nitric oxide(NO),intercellular adhesion molecule-1(ICAM-1)and thromboxane B2(TXB2)were analyzed.Results Compared with control group and radiation group,radiation+low-load decompression group showed no significant difference in the injury and death rate of rats(P＞0.05),while radiation+medium-load decompression group and radiation+high-load decompression group showed significantly increase of the injury and death rate of rats(P＜0.05).Compared with control group,other groups showed no significant change in pulmonary W/D at 3 h(P＞0.05),and increased at 72 h(P＜0.05).HE staining showed that compared with control group,radiation group showed mild lung interstitial edema,while radiation+low-load decompression group showed obvious pulmonary tissue edema and a small number of red blood cells exudated in the alveolar cavity.The edema,congestion and inflammatory cell infiltration of lung tissue were more serious in radiation+medium-load decompression group and radiation+high-load decompression group.Compared with control group and radiation group,all radiation+decompression groups showed an increase in serum levels of IL-1β,IL-6,TNF-α,MDA,NO,ICAM-1 and TXB2(P＜0.05),and a decrease in SOD activity(P＜0.05).Compared with radiation+low-load decompression group,radiation+medium-load decompression group and radiation+high-load decompression group showed increase in serum levels of IL-1β,IL-6,MDA,ICAM-1 and TXB2(P＜0.05),and decrease in activity of SOD(P＜0.05).Except for control group,serum levels of IL-1β,IL-6,TNF-α,MDA,NO,ICAM-1 and TXB2 were decreased at 72 h compared with 3 h(P＜0.05),and SOD activity was increased at 72 h in all groups(P＜0.05).Conclusions High-load decompression can increase the injury and death rate of rats exposed to radiation and high pressure.The potential mechanism of the combined injury effect of radiation and decompression was related to inflammation,immune stress,oxidative damage,vasomotor activity and coagulation mechanism.

Objective:To investigate the application value of optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in evaluating flow diverter (FD) apposition and endothelialization in aneurysm animal models, and analyze the effect of incomplete stent apposition (ISA) on aneurysm lumen healing and stent endothelialization.Methods:Lateral common carotid artery aneurysm models in swines were established by surgical method and then FD was implanted. Immediately after surgery, OCT and IVUS were used to evaluate the locations and degrees of ISA, and difference between these 2 methods in evaluating FD apposition was compared. DSA was performed at 12 weeks after surgery to evaluate the aneurysm occlusion (Kamran grading) and stent patency. OCT and IVUS were used again to observe the stent endothelial situation; by comparing with histopathologic results, effect of ISA on aneurysm healing and stent endothelialization was analyzed.Results:Lateral common carotid artery aneurysm models in 6 swines were established, and 6 Tubridge FDs were successfully implanted. Compared with IVUS (3 stents, 4 locus), OCT could detect more ISA (6 stents, 14 locus); and the vascular diameter change area (7 locus), aneurysm neck area (4 locus) and the head and tail of FD (3 locus) were the main sites of FD malapposition; average distance between stent wire and vessel wall was (560.14±101.48) μm. At 12 weeks after surgery, DSA showed that 1 patient had a little residual contrast agent at the aneurysm neck (Kamran grading 3), and the remaining 5 had complete aneurysm occlusion (Kamran grading 4). One FD had moderate lumen stenosis, and the other 5 FDs had lumen patency. OCT indicated mostly disappeared acute ISA; ISA proportion decreased to 21.4 % (3/14), including 2 in the aneurysm neck and 1 in the partial stent. Histopathological results showed bare stent woven silk, without obvious endothelial coverage; in one FD with luminal stenosis, intimal hyperplasia was mainly composed of vascular smooth muscle cells.Conclusion:In carotid artery aneurysm model with FD implantation, OCT can detect more ISA than IVUS; most acute ISA have good outcome at 12 th week of follow-up, while severe ISA can cause delayed FD endothelialization and delayed aneurysm occlusion.