[Objective] To investigate the infection status and characteristics of HEV among voluntary blood donors in Ningbo, and to provide a basis for improving the blood screening strategy. [Methods] A total of 12 227 blood samples from voluntary blood donors in Ningbo from June 2022 to May 2023 were tested for HEV serology, enzymology, and nucleic acid testing. Furthermore, HEV gene sequencing was performed for genotyping analysis, and donors with reactive nucleic acid testing results were followed up to confirm their infection status. [Results] The reactivity rate of HEV Ag, anti-HEV IgM and anti-HEV IgG was 0.098%, 0.899% and 29.198%, respectively. There was no difference in the reactivity of anti-HEV IgM and anti-HEV IgG between genders, donation frequencies and donation types (P>0.05). The reactivity rate increased significantly with age (P<0.05). The rate of ALT disqualification (ALT>50U/L) was significantly higher than that in non-reactive samples (P<0.05). The HEV Ag reactivity rate (0.098%) was not correlated with gender, donation frequency, donation type or age. One HEV RNA positive case was found, with a positive rate of 0.008%(1/12 227). It was confirmed to be hepatitis E virus genotype 3 by sequencing analysis. Apart from HEV Ag reactivity, all other blood safety screening items were non-reactive, suggesting this case might be in the acute infection phase. The follow-up results showed that all indicators of the donor's previous blood donation were non-reactive. [Conclusion] Pre-donation ALT detection can reduce the risk of transfusion-transmitted HEV (TT-HEV) to a certain extent, and the effective way to prevent TT-HEV is to detect HEV RNA and serology of donor blood.

Disrupted bone morphogenetic protein type 2 receptor (BMPR2) signaling in endothelial cells drives pulmonary arterial hypertension (PAH). However, targeted recovery of this signaling pathway by lipid nanoparticles (LNPs) has not been explored as a therapy. Here, we employed Design of Experiments to optimize the delivery efficiency of LNPs targeting pulmonary endothelial cells developed by our laboratory, resulting in a remarkable 35-fold increase in a simplified three-component formulation without helper lipids. Administration of BMPR2 mRNA LNPs effectively reversed established PAH in two experimental rat models (monocrotaline or SU5416-hypoxia) by reversing pulmonary vascular remodeling. Specifically, BMPR2 mRNA LNPs replenished the expression of BMPR2 protein and subsequently activated downstream pathways, as confirmed by elevated levels of p-SMAD1/5/9 and ID1 proteins. The relief of pulmonary arterial occlusion was demonstrated by thinned pulmonary arterial media and decreased proportion of full muscularized vessels. Alleviation of right ventricular hypertrophy was indicated by declined Fulton index, the cross-sectional area of right ventricular cardiomyocytes as well as collagen deposition. Effective recovery of right ventricular function was evidenced by increased pulmonary artery flow acceleration time/pulmonary artery flow ejection time ratio. These findings underscore the potential of restoring BMPR2 signaling through pulmonary endothelial cell-specific LNPs for treating PAH.

Salmonellosis represents a global epidemic, and the emergence of extensively drug-resistant (XDR) Salmonella and its sustained transmission worldwide constitutes a significant public health concern. Flagellum-mediated motility serves as a crucial virulence trait of Salmonella that guides the pathogen toward the epithelial surface, enhancing gut colonization. Artemisia argyit essential oil, a traditional herb extract, demonstrates efficacy in treating inflammation-related symptoms and diseases; however, its effects on flagellum assembly and expression mechanisms in anti-Salmonella activity remain inadequately explored. This study aimed to elucidate the mechanism by which Artemisia argyit essential oil addresses Salmonella infections. Network pharmacological analysis revealed that Traditional Chinese Medicine (TCM) Artemisia argyit exhibited anti-Salmonella infection potential and inhibited flagellum-dependent motility. The application of Artemisia argyit essential oil induced notable motility defects through the downregulation of flagellar and fimbriae expression. Moreover, it significantly reduced Salmonella-infected cell damage by interfering with flagellum-mediated Salmonella colonization. In vivo studies demonstrated that Artemisia argyit essential oil administration effectively alleviated Salmonella infection symptoms by reducing bacterial loads, inhibiting interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) production, and diminishing pathological injury. Gas chromatography-mass spectrometry (GC-MS) analysis identified forty-three compounds in Artemisia argyit essential oil, with their corresponding targets and active ingredients predicted. Investigation of an in vivo model of Salmonella infection using the active ingredient demonstrated that alpha-cedrene ameliorated Salmonella infection. These findings suggest the potential application of Artemisia argyit essential oil in controlling Salmonella, the predominant food-borne pathogen.
Artemisia/chemistry* ; Oils, Volatile/chemistry* ; Animals ; Flagella/drug effects* ; Salmonella Infections/microbiology* ; Humans ; Mice ; Anti-Bacterial Agents/pharmacology* ; Salmonella/pathogenicity*

Objective To investigate the expression of 8-hydroxy deoxy guanosine(8-OHdG)and nectin-4 in the serum of primary liver cancer(PLC),and to evaluate the efficacy of transcatheter chemoembolization(TACE)for PLC.Methods From January 2021 to June 2022,180 patients with primary liver cancer with TACE were studied.According to the efficacy of TACE patients,they were separated into a good group(n=137)and an adverse group(n=43).The general clinical data and the serum expression levels of 8-OHdG and nectin-4 were compared between the two groups;multivariate Logistic regression was applied to analyze the influencing factors of postoperative efficacy in TACE for primary liver cancer;receiver operating characteristic was applied to analyze the value of serum 8-OHdG and nectin-4 levels in evaluating the efficacy of TACE for primary liver cancer.Results There were no significant differences in age,sex,BMI,Child-Pugh grade,tumor location,tumor number,tumor diameter,tumor contour,degree of differentiation,tumor envelope,vascular cancer thrombus,bile duct cancer thrombus and lymph node metastasis between the poor postoperative efficacy group and the good efficacy group after TACE for primary liver cancer(P＞0.05).The expression levels of serum 8-OHdG and nectin-4 in the poor postoperative efficacy group after TACE for primary liver cancer were obviously higher than those in the good efficacy group(P＜0.05).Multivariate Logistic regression analysis showed that serum 8-OHdG,nectin-4,tumor diameter,TNM staging and Lymph node metastasis were all independent influencing factors for the postoperative efficacy of TACE in primary liver cancer(P＜0.05).The AUC of the combined evaluation of serum 8-OHdG and nectin-4 for the postoperative efficacy of TACE in primary liver cancer was 0.930,with a sensitivity of 86.05％and a specificity of 94.16％,which was superior to their respective individual evaluations(Zcombination-8-OHdG=2.033,Zcombination-nectin-4=3.221,P=0.042,0.001).Conclusion The serum levels of 8-OHdG and nectin-4 are obviously increased in the poor postoperative efficacy group after TACE for primary liver cancer.The combination of the two has a good evaluation effect on the postoperative efficacy of TACE for primary liver cancer.

Objective To evaluate the safety, effectiveness and feasibility of robotic-assisted kidney transplantation (RAKT). Methods Clinical data of 16 patients who underwent kidney transplantation were collected. Among them, 8 recipients received RAKT (RAKT group) and 8 cases underwent open kidney transplantation (OKT) with the contralateral kidney from the same donor (OKT group). Perioperative status and the recovery of renal allograft function were compared between two groups. Results All patients successfully completed the surgery. In the RAKT group, no patient was converted to open surgery. The operation time in the RAKT group was longer than that in the OKT group (P=0.015). No significant differences were observed in the serum creatinine levels before surgery and upon discharge between two groups (both P>0.05). In the OKT group, one recipient developed delayed graft function (DGF), and the remaining recipients did not experience perioperative complications. No significant difference was noted in the short-term recovery of renal allograft function between two groups (P>0.05). Conclusions Postoperative recovery of the recipients in the RAKT group is equivalent to that of their counterparts in the OKT group. RAKT is a safe and effective procedure for the team expertise in kidney transplantation.

Objective:To evaluate the efficacy of preoperative three-dimensional (3D) image reconstruction combined with intraoperative dynamic ultrasonography (IOUS) in laparoscopic precision hepatectomy for intrahepatic bile duct stones.Methods:The clinical data of 66 patients with intrahepatic bile duct stones undergoing laparoscopic hepatectomy in the First People's Hospital of Fuyang District, Hangzhou from January 2018 to January 2023 were retrospectively analyzed, including 32 males and 34 females, aged (49.6±15.2) years old. Patients were divided into the study group ( n=32), who underwent laparoscopic precision hepatectomy using 3D reconstruction combined with IOUS, and the control group ( n=34), who underwent conventional laparoscopic hepatectomy. Perioperative data including the operation time, intraopera-tive blood loss, total volume of drainage on postoperative day (POD) 3, and the rates of complications were compared between the groups. Serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), liver function indices including total bilirubin (TBil) and alanine aminotransferase (ALT) were monitored preoperatively and on POD 1, 3, 5, and 7. Results:The operation time was shorter in the study group [(178±17) min vs. (189±18) min, t=2.55, P=0.010]. The intraoperative blood loss was reduced in the study group [(218±19) ml vs. (395±21) ml, P<0.001]. The incidence of total volume of drainage >300 ml on POD 3 were comparable between the groups [9.4%(3/32) vs. 14.7%(5/34), P=0.507]. There were no significant differences in preoperative serum level of TBil, ALT, CRP and IL-6 between the groups (all P>0.05). Compared to the control group, serum levels of TBil, ALT and CRP in the study group were decreased on POD 1, 3, 5 and 7, and IL-6 was decreased on POD 1 and 3 (all P<0.05). The occurrences of postoperative bile leakage [9.4% (3/32) vs. 29.4% (10/34)] and liver cutting surface fluid accumulation [12.5% (4/32) vs. 35.3% (12/34)] and the rate of stone retention [3.0% (1/32) vs. 20.6% (7/34)] were lower in the study group (all P<0.05). Conclusion:Preoperative 3D image reconstruction combined with IOUS in laparoscopic precision hepatectomy for intrahepatic bile duct stones could reduce intra-operative blood loss, hepatic inflammatory response, and postoperative complications.

Diabetic neuropathic pain (DNP) is the most common disabling complication of diabetes. Emerging evidence has linked the pathogenesis of DNP to the aberrant sprouting of sensory axons into the epidermal area; however, the underlying molecular events remain poorly understood. Here we found that an axon guidance molecule, Netrin-3 (Ntn-3), was expressed in the sensory neurons of mouse dorsal root ganglia (DRGs), and downregulation of Ntn-3 expression was highly correlated with the severity of DNP in a diabetic mouse model. Genetic ablation of Ntn-3 increased the intra-epidermal sprouting of sensory axons and worsened the DNP in diabetic mice. In contrast, the elevation of Ntn-3 levels in DRGs significantly inhibited the intra-epidermal axon sprouting and alleviated DNP in diabetic mice. In conclusion, our studies identified Ntn-3 as an important regulator of DNP pathogenesis by gating the aberrant sprouting of sensory axons, indicating that Ntn-3 is a potential druggable target for DNP treatment.
Mice ; Animals ; Diabetes Mellitus, Experimental/metabolism* ; Axons/physiology* ; Diabetic Neuropathies ; Sensory Receptor Cells/metabolism* ; Neuralgia/metabolism*

Cellular senescence is a response process in which cells are activated by ischemia, hypoxia, oxidative stress, DNA damage, reactive oxygen species deposition and other stimulations.Senescent cells markers include such as senescence-associated β-galactosidase (SA-β-gal) activation, P16INK4a upregualtion, senescence-associated heterochromatic foci (SAHF) accumulation, senescence-associated secretory phenotype (SASP) generation, telomere shortening and so on.P16INK4a/Rb and P19 ARF/P53/P21 Cip1 pathways are two classic cell senescence signaling pathways, which are interconnected and independent on each other.In recent years, glaucoma is considered as a blinding eye disease associated with cell senescence.Research on cell senescence in glaucoma mainly focuses on trabecular meshwork and Schlemm cannel endothelial cells senescence leading to increased resistance of aqueous humor outflow pathway, and the mechanism of retinal ganglion cells senescence and treatment in glaucoma.As an irreversible stage before cell death, deeper study on the mechanism of retinal ganglion cells senescence, and specific blocking of cell senescence will provide a new target for reducing the aqueous humor outflow resistance and protecting the optic nerve in glaucoma.This article reviewed characteristics, inducements, molecular signaling pathways of cellular senescence in glaucoma.

Objective: To discuss the correlation between the extraction timing of mesiodens and the orthodontic treatment duration of its eruption-related complications in children to provide a reference for the clinic. Methods : The mesiodentes of 187 children were classified as eruption type (typeⅠ), dental crown impacted type (type Ⅱ), interdental impacted type (type Ⅲ), and dental root impacted type (type Ⅳ). According to the timing of extraction, mesiodentes in typeⅠ, type Ⅲ, and type Ⅳ were divided into Groups A: before the eruption of the adjacent central incisor and B: after the eruption of the adjacent central incisor. Mesiodentes in type Ⅱ were divided into Group A: before the eruption of the contralateral central incisor and B: after the eruption of the contralateral central incisor. Eruption-related complications and orthodontic treatment durations caused by mesiodens were statistically analyzed. Results : There were 106 cases of displacement, 28 cases of failed eruption, 27 cases of tooth rotation, and 26 cases of individual cross-bite among the eruption-related complications caused by mesiodens. The mean orthodontic treatment cycle in Group A of type Ⅰ (7.07 ± 2.45 month), Group A of type Ⅱ (6.57 ± 1.12 month), and Group A of type Ⅲ (6.95 ± 2.52 month) were lower than that in Group B of type Ⅰ (9.67 ± 3.04 month), Group B of type Ⅱ (10.25 ± 1.29 month), and Group B of type Ⅲ (9.33 ± 3.26 month), and the differences were statistically significant (P<0.01). Meanwhile, there was no significant difference in the mean orthodontic treatment duration between Groups A (6.00 ± 0.94 month) and B (6.33 ± 0.80 month) of type Ⅳ (P>0.05). Conclusion In most cases, the mesiodens are removed before the eruption of the adjacent central incisor, which can reduce the duration of orthodontic treatment for eruption-related complications in children.

Objective:To confirm the efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit.Methods:This study is a subgroup analysis of multi-center, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial. A total 812 patients of acute ischemic stroke with obvious limb motor deficit [motor function of limbs score in National Institutes of Health Stroke Scale (NIHSS) ≥4] were enrolled in this subgroup analysis. Patients received either cinepazide maleate injection or placebo. The treatment period was 14 days and follow-up was 90 days. The efficacy endpoints included the proportions of patients with a modified Rankin Scale (mRS) score ≤2, mRS score ≤1 and Barthel Index <95 on day 90. Safety was evaluated by recording all adverse events, monitoring vital signs, laboratory parameters and electrocardiogram.Results:A total of 732 patients were involved in the final efficacy analysis (361 in cinepazide maleate group and 371 in control group). The baseline limb motor function score of NIHSS was 5.23±1.43 in the cinepazide maleate group whereas 5.20±1.36 in the control group. Logistic regression analysis showed that following treatment for 90 days, the proportion of patients with a mRS score ≤2 was significantly higher in the cinepazide maleate group than in the control group [56.0% (202/361) vs 44.2% (164/371), OR=0.60, 95% CI 0.44-0.82, P=0.002]. The proportion of patients with a mRS score ≤1 was higher in the cinepazide maleate group than in the control group [43.3% (139/361) vs 35.2% (118/371), OR=0.69, 95% CI 0.50-0.97, P=0.031]. The proportion of patients with a Barthel Index <95 on day 90 was significantly lower in the cinepazide maleate group than in the control group [45.2% (145/361) vs 55.2% (185/371), OR=0.64, 95% CI 0.46-0.88, P=0.007]. During the treatment and follow-up period, the incidence of the most common adverse events in the cinepazide maleate group was 50.4% (199/395). Constipation and abnormal liver function were more common, but there were no statistically significant differences between the two groups. Conclusion:Cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery and safe in patients with acute ischemic stroke with obvious limb motor deficit.