Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

OBJECTIVE: To evaluate the anti-hepatocellular carcinoma (HCC) activity of total alkaloids from Gelsemium elegans Benth. (TAG) in vivo and in vitro and to elucidate their potential mechanisms of action through transcriptomic analysis. METHODS: TAG extraction was conducted, and the primary components were quantified using high-performance liquid chromatography (HPLC). The effects of TAG (100, 150, and 200 µg/mL) on various tumor cells, including SMMC-7721, HepG2, H22, CAL27, MCF7, HT29, and HCT116, were assessed. Effects of TAG on HCC proliferation and apoptosis were detected by colony formation assays and cell stainings. Caspase-3, Bcl-2, and Bax protein levels were detected by Western blotting. In vivo, a tumor xenograft model was developed using H22 cells. Totally 40 Kunming mice were randomly assigned to model, cyclophosphamide (20 mg/kg), TAG low-dose (TAG-L, 0.5 mg/kg), and TAG high-dose (TAG-H, 1 mg/kg) groups, with 10 mice in each group. Tumor volume, body weight, and tumor weight were recorded and compared during 14-day treatment. Immune organ index were calculated. Tissue changes were oberseved by hematoxylin and eosin staining and immunohistochemistry. Additionally, transcriptomic and metabolomic analyses, as well as quatitative real-time polymerase chain reaction (RT-qPCR), were performed to detect mRNA and metabolite expressions. RESULTS: HPLC successfully identified the components of TAG extraction. Live cell imaging and analysis, along with cell viability assays, demonstrated that TAG inhibited the proliferation of SMMC-7721, HepG2, H22, CAL27, MCF7, HT29, and HCT116 cells. Colony formation assays, Hoechst 33258 staining, Rhodamine 123 staining, and Western blotting revealed that TAG not only inhibited HCC proliferation but also promoted apoptosis (P<0.05). In vivo experiments showed that TAG inhibited the growth of solid tumors in HCC in mice (P<0.05). Transcriptomic analysis and RT-qPCR indicated that the inhibition of HCC by TAG was associated with the regulation of the key gene CXCL13. CONCLUSION TAG inhibits HCC both in vivo and in vitro, with its inhibitory effect linked to the regulation of the key gene CXCL13.
Animals ; Apoptosis/drug effects* ; Liver Neoplasms/genetics* ; Carcinoma, Hepatocellular/genetics* ; Humans ; Alkaloids/therapeutic use* ; Gelsemium/chemistry* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Mice ; Xenograft Model Antitumor Assays

Hepatocellular carcinoma(HCC), the third leading cause of cancer-related death worldwide, is characterized by high mortality and recurrence rates. Common treatments include hepatectomy, liver transplantation, ablation therapy, interventional therapy, radiotherapy, systemic therapy, and traditional Chinese medicine(TCM). While exhibiting specific advantages, these approaches are associated with varying degrees of adverse effects. To alleviate patients' suffering and burdens, it is crucial to explore additional treatments and elucidate the pathogenesis of HCC, laying a foundation for the development of new TCM-based drugs. With emerging research on gut microbiota, it has been revealed that microbiota plays a vital role in the development of HCC by influencing intestinal barrier function, microbial metabolites, and immune regulation. TCM, with its multi-component, multi-target, and multi-pathway characteristics, has been increasingly recognized as a vital therapeutic treatment for HCC, particularly in patients at intermediate or advanced stages, by prolonging survival and improving quality of life. Recent global studies demonstrate that TCM exerts anti-HCC effects by modulating gut microbiota, restoring intestinal barrier function, regulating microbial composition and its metabolites, suppressing inflammation, and enhancing immune responses, thereby inhibiting the malignant phenotype of HCC. This review aims to elucidate the mechanisms by which gut microbiota contributes to the development and progression of HCC and highlight the regulatory effects of TCM, addressing the current gap in systematic understanding of the "TCM-gut microbiota-HCC" axis. The findings provide theoretical support for integrating TCM with western medicine in HCC treatment and promote the transition from basic research to precision clinical therapy through microbiota-targeted drug development and TCM-based interventions.
Humans ; Gastrointestinal Microbiome/drug effects* ; Carcinoma, Hepatocellular/microbiology* ; Liver Neoplasms/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Medicine, Chinese Traditional

Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

This study aims to investigate the effects of aflatoxin B1(AFB1)on the infection and replication of porcine delta coronavirus(PDCoV).Porcine small intestinal epithelial cells(IPEC-J2),porcine kidney cells(LLC-PK)and swine testis cells(ST)were used as models,and CCK-8 method was used to detect the safe mass concentration range of AFB1 on the three cell lines.Each cell line was divided into the blank control group,AFB1 treatment group,PDCoV treatment group and AFB1 and the PDCoV co-treatment group.The cells were treated with safe mass concentration of AFB1 for 12 h,and then treated with PDCoV for 20 h.Total RNA and total protein were extrac-ted from the cells.The effects of AFB1 on PDCoV infection and replication were detected by qPCR,Western blot and cell immunofluorescence tests.The results showed that compared with the PDCoV treatment group,the mRNA and N protein of viral S protein in the AFB1 and PDCoV co-treatment group were significantly increased(P＜0.05),and a significantly higher fluorescence of PDCoV N protein is also visibly present in the co-treatment group,and there was a significant difference between the two groups.The results showed that AFB1 could promote the infection and replication of PDCoV.It provides important data that AFB1 can promote the infection replication of PDCoV and provides a new idea for the prevention and treatment of PDCoV.

Objective To investigate the differences in demographic characteristics,reproductive health status,and the distribution of pregnancy-related diseases between couples conceived via assisted reproductive technology(ART)and naturally conceived couples,and to analyze the impact of ART treatment on the incidence of preterm birth(PTB)in singleton and twin and multiple pregnancies.Methods We conducted a retrospective analysis of the maternal and infant cohort data of Jing'an District from 2013 to 2020.Based on the conception method,the subjects were categorized into two groups:the ART group and the natural conception group.Chi-square test was applied to compare baseline characteristics and disease distributions differences between the two groups,and logistic regression models were used to evaluate the association between ART and the PTB risks.A causal mediation model was used to evaluate the mediating effect of twin and multiple pregnancy in the relationship between ART and PTB.Results A total of 117 717 parturients were included,6 265 in the ART group and 111 452 in the natural conception group.Compared with the natural conception group,couples in the ART group were significantly older and had a higher prevalence of reproductive system diseases.The incidences of diabetes and hypertensive disorders during pregnancy in ART parturient were 13.76%and 9.99%,respectively,which were significantly higher than 7.88%and 4.75%in the natural conception group(both P<0.001).The overall PTB rate in the ART group was 14.81%,higher than 5.35%in the natural conceptions group(P<0.001).The PTB rate in ART for singleton pregnancies in the ART group was 6.40%,higher than 4.83%in the natural conception group(P<0.001),while the PTB rate in ART for twin and multiple pregnancies in the ART group was 53.97%,lower than 60.42%in the natural conception group(P<0.05).Mediation analysis showed that 97.99%of the effect of ART on PTB was mediated by twin and multiple pregnancy,with ART increasing the PTB risk by 3.44 times through multiple pregnancy.Conclusion The overall PTB rate of ART recipients is higher than that of natural recipients,but ART does not increase the PTB risk in singleton and twin and multiple pregnancies.Twin and multiple pregnancy is the key mediating factor contributing to PTB in ART-conceived recipients.Compared with naturally conceived couples,ART conception couples own more advanced maternal age,and have higher risks of suffering gestational diabetes,gestational hypertension,and PTB.

Objective To investigate the differences in demographic characteristics,reproductive health status,and the distribution of pregnancy-related diseases between couples conceived via assisted reproductive technology(ART)and naturally conceived couples,and to analyze the impact of ART treatment on the incidence of preterm birth(PTB)in singleton and twin and multiple pregnancies.Methods We conducted a retrospective analysis of the maternal and infant cohort data of Jing'an District from 2013 to 2020.Based on the conception method,the subjects were categorized into two groups:the ART group and the natural conception group.Chi-square test was applied to compare baseline characteristics and disease distributions differences between the two groups,and logistic regression models were used to evaluate the association between ART and the PTB risks.A causal mediation model was used to evaluate the mediating effect of twin and multiple pregnancy in the relationship between ART and PTB.Results A total of 117 717 parturients were included,6 265 in the ART group and 111 452 in the natural conception group.Compared with the natural conception group,couples in the ART group were significantly older and had a higher prevalence of reproductive system diseases.The incidences of diabetes and hypertensive disorders during pregnancy in ART parturient were 13.76%and 9.99%,respectively,which were significantly higher than 7.88%and 4.75%in the natural conception group(both P<0.001).The overall PTB rate in the ART group was 14.81%,higher than 5.35%in the natural conceptions group(P<0.001).The PTB rate in ART for singleton pregnancies in the ART group was 6.40%,higher than 4.83%in the natural conception group(P<0.001),while the PTB rate in ART for twin and multiple pregnancies in the ART group was 53.97%,lower than 60.42%in the natural conception group(P<0.05).Mediation analysis showed that 97.99%of the effect of ART on PTB was mediated by twin and multiple pregnancy,with ART increasing the PTB risk by 3.44 times through multiple pregnancy.Conclusion The overall PTB rate of ART recipients is higher than that of natural recipients,but ART does not increase the PTB risk in singleton and twin and multiple pregnancies.Twin and multiple pregnancy is the key mediating factor contributing to PTB in ART-conceived recipients.Compared with naturally conceived couples,ART conception couples own more advanced maternal age,and have higher risks of suffering gestational diabetes,gestational hypertension,and PTB.

This study aims to investigate the effects of aflatoxin B1(AFB1)on the infection and replication of porcine delta coronavirus(PDCoV).Porcine small intestinal epithelial cells(IPEC-J2),porcine kidney cells(LLC-PK)and swine testis cells(ST)were used as models,and CCK-8 method was used to detect the safe mass concentration range of AFB1 on the three cell lines.Each cell line was divided into the blank control group,AFB1 treatment group,PDCoV treatment group and AFB1 and the PDCoV co-treatment group.The cells were treated with safe mass concentration of AFB1 for 12 h,and then treated with PDCoV for 20 h.Total RNA and total protein were extrac-ted from the cells.The effects of AFB1 on PDCoV infection and replication were detected by qPCR,Western blot and cell immunofluorescence tests.The results showed that compared with the PDCoV treatment group,the mRNA and N protein of viral S protein in the AFB1 and PDCoV co-treatment group were significantly increased(P＜0.05),and a significantly higher fluorescence of PDCoV N protein is also visibly present in the co-treatment group,and there was a significant difference between the two groups.The results showed that AFB1 could promote the infection and replication of PDCoV.It provides important data that AFB1 can promote the infection replication of PDCoV and provides a new idea for the prevention and treatment of PDCoV.

Objective To observe the effect of intra-arterial nimodipine perfusion after interventional embolization in the treatment of symptomatic cerebral vasospasm(SCVS)after aneurysmal subarachnoid hemorrhage(aSAH)and explore its influence on vascular endothelial function.Methods Patients with SCVS after aSAH were divided into treatment group and control group according to cohort methods.Both groups received interventional embolization based on symptomatic supportive treatment,and were given conventional 3H treatments such as blood dilution,dilatation and pressure enhancement after surgery,and the treatment group was additionally given intra-arterial perfusion of nimodipine(20％nimodipine was injected by electronic pump through the femoral artery sheath at a rate of 0.2 mg·min-1 for 2 mg once a day,vascular sheath was removed and nimodipine tablet after 7 days of medication was taken orally for 60-120 mg twice a day after meals),and both groups were treated for 14 days.The cerebrovascular blood flow velocity,laboratory indicators,postoperative complications and prognosis were compared between the two groups.Results There were 41 cases in treatment group,and 38 cases in control group.After 2 weeks of treatment,the average blood flow velocities of anterior cerebral artery(ACA)in treatment group and control group were(84.32±5.27)and(93.46±5.61)cm·s-1,the average blood flow velocities of middle cerebral artery(MCA)were(86.05±5.94)and(95.23±6.37)cm·s-1,the average blood flow velocities of posterior cerebral artery(PCA)were(59.41±4.82)and(71.56±5.39)cm·s-1 respectively(all P＜0.05).The levels of serum endothelin-1(ET-1)in treatment group and control group after 2 weeks of treatment were(76.32±10.58)and(94.16±10.98)pg·mL-1;the levels of vascular endothelial growth factor(VEGF)were(127.45±14.83)and(164.85±15.62)ng·mL-1;the levels of soluble fms-like tyrosine kinase-1(sFlt-1)were(103.67±15.34)and(114.98±16.43)ng·L-1;the levels of plasma soluble intercellular adhesion molecule-1(sCAM-1)were(234.81±62.79)and(285.36±90.24)ng·mL-1;the levels of hypoxia-inducible factor-2α(HIF-2α)were(98.74±7.56)and(102.49±8.35)pg·mL-1;the levels of serum nitric oxide(NO)were(43.16±4.91)and(39.72±5.37)mmol·L-1,all with significant difference(all P＜0.05).The incidence rates of delayed cerebral vasospasm(DCVS)and hydrocephalus were 4.88％and 9.76％in treatment group after surgery,lower than 21.05％and 28.95％in control group(all P＜0.05).The proportion of Glasgow outcome scale(GOS)score of 5 points in treatment group at 3 months after surgery was higher than that in control group(78.05％vs 55.26％,P＜0.05).Conclusion After interventional embolization,intra-arterial perfusion of nimodipine for SCVS after aSAH can help to relieve the inflammatory response,improve the vascular endothelial function and reduce the cerebral blood flow velocity,and it plays a positive role on reducing the cerebral tissue injury and improving the prognosis of patients.

Objective To investigate the protective effect of berberine on the injury of colon epithelial cells induced by dextran sulfate sodium(DSS).Methods NCM-460 cells were randomly divided into blank group(conventional culture),model group(40 mg·mL-1 DSS)and low-dose group(5 μmol·L-1 berberine),high-dose group(10 μmol·L-1 berberine),siRNA group(10 μmol·L-1 berberine+transfected siRNA plasmid),si-SelS group(10 μmol·L-1 berberine+transfected si-SelS plasmid).The expressions of selenioprotein S(SelS)were detected by Western blot;cell proliferation was detected by cell counting kit-8(CCK-8)and 5-ethynyl-2'-deoxyuridine(EdU)tests;trans epithellal electric resistance(TEER)levels were detected by Milli-cell ERS;superoxide dismutase(SOD)was detected by kit method;apoptosis was detected by flow cytometry.Results The relative expression levels of SelS protein in blank group,model group,high-dose group,siRNA group and si-SelS group were 1.02±0.13,0.42±0.05,0.90±0.08,0.89±0.10 and 0.30±0.03,respectively;the cell optical density at 48 h were 0.85±0.05,0.48±0.04,0.70±0.08,0.68±0.05 and 0.51±0.05,respectively;the EdU positive cell rates were(33.78±2.72)％,(11.90±2.00)％,(25.74±1.94)％,(24.29±1.96)％and(15.17±1.16)％,respectively;TEER values were(100.00±3.64)％,(43.47±4.19)％,(73.28±7.38)％,(76.25±7.68)％and(53.49±4.42)％,respectively;SOD activities were(13.32±0.73),(5.33±0.55),(9.63±1.13),(9.69±0.88)and(6.40±0.57)U·mL-1,respectively;the apoptosis rates were(3.21±0.02)％,(24.59±2.35)％,(10.90±1.09)％,(11.11±1.24)％and(16.73±1.56)％,respectively.The above indexes in the model group were compared with those in the blank group,and those in the high-dose group were compared with those in the model group.The above indexes of si-SelS group were statistically significant compared with those of siRNA group(all P＜0.05).Conclusion Berberine can inhibit oxidative stress and improve DSS induced colon epithelial cell barrier damage by up-regulating SelS.