Objective To investigate the effect of the Nogo receptor antagonist NEP1-40,administered via an exogenous route,on axonal regeneration in rats with spinal cord injury(SCI),and to explore its mecha-nism of action in the process of neural repair.Methods SD rats were divided into a sham surgery group(Group A),an injury group(Group B),and an injury+NEP1-40 treatment group(Group C).In Group A,only laminectomy was performed without spinal cord injury.Groups B and C were subjected to a clip-type SCI model.Group C received treatment with NEP1-40 based on the established SCI model.Hindlimb motor func-tion in the three groups was assessed using the BBB score at 1,3,7,and 14 days post-surgery.Real-time quan-titative PCR(qPCR)and Western blot were used to detect changes in gene and protein expression levels of growth-associated protein-43(GAP-43)and microtubule-associated protein-2(MAP-2),characteristic markers of axonal and dendritic regeneration.Immunofluorescence was employed to analyze NF-200 and BrdU double-labeling,and changes in the number of double-labeled positive cells were observed and analyzed.Results In group A rats,the BBB scores at various time points after surgery showed no significant change compared with preoperative scores.In groups B and C,the BBB scores on postoperative day 1 were obviously lower than pre-operative scores.From days 3 to 14 after surgery,the BBB scores partially recovered compared with postopera-tive day 1,though they remained lower than those in group A.However,on postoperative days 3,7,and 14,the BBB scores in group C were higher than those in group B(P<0.05).qPCR and Western blot results showed that compared with preoperative levels,GAP-43 and MAP-2 mRNA and protein expression in groups B and C at postoperative days 3,7,and 14 showed a trend of first decreasing and then increasing,and the expression in group C was consistently higher than in group B(P<0.05).The expression level of NogoA in group C showed an opposite trend to GAP-43 and MAP-2.Compared with preoperative levels,NogoA mRNA and pro-tein expression in group B rats decreased on postoperative days 1 and 3(P<0.05)and increased on days 7 and 14(P<0.05).Compared with preoperative levels,NogoA mRNA and protein expression in groups B and C also showed a trend of first decreasing and then increasing,but in group C,at all postoperative time points except day 1,it was lower than in group B(P<0.05).Immunofluorescence results showed that over time,the number of cells double-labeled with BrdU and NF-200 gradually increased,with the highest number observed in group C on postoperative day 14.Conclusion NEP1-40 promotes neurological repair in SCI,providing a new approach for SCI repair treatment.

In order to investigate the mitigating effect of Yin Chen aqueous extract on liver injury induced by LPS combined with D-GalN in mice,a mouse liver injury model was established by in-traperitoneal injection of LPS and D-GalN,and the mice were group-fed by instillation of saline,bi-phenyl dibenzyl ester,and Yin Chen aqueous extract with different concentrations of LPS and D-GalN.The liver index of mice was calculated,pathological tissue sections were observed,and the expression of ALT,AST,inflammatory cytokines,oxidative stress,hepatic enzymes,and IL-17/TNF pathway were detected in serum to investigate the effects and mechanisms of the aqueous ex-tracts of Yin Chen in alleviating the liver injury in mice.The results showed that the liver index of mice in the model group was significantly elevated,the serum levels of ALT and AST were signifi-cantly elevated,the levels of IL-iβ,IL-8 and TNF-α in liver tissue were significantly elevated,the levels of IL-4 were significantly reduced,the levels of GSH-Px,CAT and SOD were significantly reduced,the levels of ROS and MDA were significantly elevated,CYP2E1 and CYP1A2 protein content and mRNA expression were significantly up-regulated,and the expression levels of TNF,TNFR1,IL-17A,ACT1 and IL-6 mRNA were significantly up-regulated.The study showed that the aqueous extract of Yin Chen had a certain alleviating effect on the liver injury caused by LPS combined with D-GalN in mice.The mechanism of action includes decreasing the metabolic level of hepatic drug enzymes,alleviating oxidative stress,inhibiting the expression of IL-17/TNF pathway and down-regulating the level of inflammatory factors in mice.

Tuberculosis,as a chronic infectious disease caused by Mycobacterium tuberculosis(MTB)infection,presenting a serious threat to human and animal health.When human body is infected by MTB,it quickly initiates an immune response,in which T lymphocyte-mediated cellular immunity plays a key role,as it can effectively recog-nize and eliminate MTB,serving as an important defense line for the body against MTB.However,during MTB in-fection process,myeloid-derived suppressor cells(MDSCs)undergo amplification and activation,which exhibit in-hibitory effect on the immune function of T lymphocytes and interfere the normal immune response of the body,making MTB easier to survive and reproduce in the body.This article discusses the role of MDSCs in the occu-rrence,development and prognosis of tuberculosis from two different perspectives,expects to provide new perspec-tives and ideas for the immunotherapy of tuberculosis as well as the research and development of targeted drugs,so as to open up a new way for the prevention and treatment of tuberculosis.

Objective To investigate the application of offline solid-phase extraction-high performance liquid chromatography-tandem mass spectrometry for detecting four synthetic cannabinoids(5F-ADB,5F-MDMB-PICA,4F-MDMB-BUTINACA,and MDMB-4en-PINACA)and their marker metabolites in urban wastewater.Methods Samples were pre-treated using an Oasis PRiME HLB column(60 mg,3CC)and analyzed by ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry.The mobile phases consisted of 0.02%formic acid-2 mmol/L ammonium formate aqueous solution and acetonitrile solution,with a WATERS ACQUITY UPLCHSS T3 column.Analysis was conducted in positive ionization mode of the ESI ion source,combining multiple reaction monitoring(MRM),information-dependent acquisition(IDA),and enhanced product ion(EPI)scanning modes for qualitative and quantitative analysis of the eight target compounds.Results Good linearity was observed for 4F-MDMB-BUTINACA-M,5F-ADB,5F-ADB-M,and 5F-MDMB-PICA in the concentration range of 1～250 ng/L;for MDMB-4en-PINACA in the range of 5～250 ng/L;and for 4F-MDMB-BUTINACA,5F-MDMB-PICA-M,and 4F-MDMB-BUTINACA-M in the range of 1～500 ng/L.The recovery rates of samples spiked with different concentrations of the eight target compounds ranged from 87.68%to 104.68%,with matrix effects between 88.61%and 112.78%.Both intra-day and inter-day precision were less than 5%.Conclusion The established method demonstrates good accuracy and reproducibility,making it suitable for qualitative and quantitative detection of four synthetic cannabinoids and their metabolites in urban wastewater.

Tuberculosis,as a chronic infectious disease caused by Mycobacterium tuberculosis(MTB)infection,presenting a serious threat to human and animal health.When human body is infected by MTB,it quickly initiates an immune response,in which T lymphocyte-mediated cellular immunity plays a key role,as it can effectively recog-nize and eliminate MTB,serving as an important defense line for the body against MTB.However,during MTB in-fection process,myeloid-derived suppressor cells(MDSCs)undergo amplification and activation,which exhibit in-hibitory effect on the immune function of T lymphocytes and interfere the normal immune response of the body,making MTB easier to survive and reproduce in the body.This article discusses the role of MDSCs in the occu-rrence,development and prognosis of tuberculosis from two different perspectives,expects to provide new perspec-tives and ideas for the immunotherapy of tuberculosis as well as the research and development of targeted drugs,so as to open up a new way for the prevention and treatment of tuberculosis.

Objective To investigate the application of offline solid-phase extraction-high performance liquid chromatography-tandem mass spectrometry for detecting four synthetic cannabinoids(5F-ADB,5F-MDMB-PICA,4F-MDMB-BUTINACA,and MDMB-4en-PINACA)and their marker metabolites in urban wastewater.Methods Samples were pre-treated using an Oasis PRiME HLB column(60 mg,3CC)and analyzed by ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry.The mobile phases consisted of 0.02%formic acid-2 mmol/L ammonium formate aqueous solution and acetonitrile solution,with a WATERS ACQUITY UPLCHSS T3 column.Analysis was conducted in positive ionization mode of the ESI ion source,combining multiple reaction monitoring(MRM),information-dependent acquisition(IDA),and enhanced product ion(EPI)scanning modes for qualitative and quantitative analysis of the eight target compounds.Results Good linearity was observed for 4F-MDMB-BUTINACA-M,5F-ADB,5F-ADB-M,and 5F-MDMB-PICA in the concentration range of 1～250 ng/L;for MDMB-4en-PINACA in the range of 5～250 ng/L;and for 4F-MDMB-BUTINACA,5F-MDMB-PICA-M,and 4F-MDMB-BUTINACA-M in the range of 1～500 ng/L.The recovery rates of samples spiked with different concentrations of the eight target compounds ranged from 87.68%to 104.68%,with matrix effects between 88.61%and 112.78%.Both intra-day and inter-day precision were less than 5%.Conclusion The established method demonstrates good accuracy and reproducibility,making it suitable for qualitative and quantitative detection of four synthetic cannabinoids and their metabolites in urban wastewater.

In order to investigate the mitigating effect of Yin Chen aqueous extract on liver injury induced by LPS combined with D-GalN in mice,a mouse liver injury model was established by in-traperitoneal injection of LPS and D-GalN,and the mice were group-fed by instillation of saline,bi-phenyl dibenzyl ester,and Yin Chen aqueous extract with different concentrations of LPS and D-GalN.The liver index of mice was calculated,pathological tissue sections were observed,and the expression of ALT,AST,inflammatory cytokines,oxidative stress,hepatic enzymes,and IL-17/TNF pathway were detected in serum to investigate the effects and mechanisms of the aqueous ex-tracts of Yin Chen in alleviating the liver injury in mice.The results showed that the liver index of mice in the model group was significantly elevated,the serum levels of ALT and AST were signifi-cantly elevated,the levels of IL-iβ,IL-8 and TNF-α in liver tissue were significantly elevated,the levels of IL-4 were significantly reduced,the levels of GSH-Px,CAT and SOD were significantly reduced,the levels of ROS and MDA were significantly elevated,CYP2E1 and CYP1A2 protein content and mRNA expression were significantly up-regulated,and the expression levels of TNF,TNFR1,IL-17A,ACT1 and IL-6 mRNA were significantly up-regulated.The study showed that the aqueous extract of Yin Chen had a certain alleviating effect on the liver injury caused by LPS combined with D-GalN in mice.The mechanism of action includes decreasing the metabolic level of hepatic drug enzymes,alleviating oxidative stress,inhibiting the expression of IL-17/TNF pathway and down-regulating the level of inflammatory factors in mice.

AIM:To investigate the effect of circular RNA MYO9A-006(circMYO9A_006)on hypertrophic phenotype of cardiomyocytes and the underlying mechanism.METHODS:The effect of adenovirus-mediated overexpres-sion of circMYO9A_006 on the expression of hypertrophy-related proteins,including β-myosin heavy chain(β-MHC),skeletal muscle actin alpha 1(ACTA1)and atrial natriuretic peptide(ANP),was evaluated in neonatal mouse ventricular cardiomyocytes(NMVCs).Moreover,a neonatal rat ventricular cardiomyocyte(NRVC)model of phenylephrine(PE)-in-duced hypertrophy was established.The effect of circMYO9A_006 overexpression on NRVC size was ascertained using Phalloidin-iFluor 647 staining method.Dual-luciferase reporter assay was employed to measure the activity of potential in-ternal ribosome entry sites(IRES)in circMYO9A_006.The translation and intracellular location of the circMYO9A_006-translated protein,MYO9A-208aa,were verified using Western blot.To investigate the role of MYO9A-208aa in the ef-fect of circMYO9A_006 on the cardiomyocyte hypertrophic phenotype,we prepared and used the following adenoviruses:the recombinant circMYO9A_006-ORF adenovirus to express MYO9A-208aa,the recombinant circMYO9A_006-ATG-mut adenovirus that does not express MYO9A-208aa,the recombinant circMYO9A_006 adenovirus,and the adenovirus vector control.These were then employed to infect NRVCs.RESULTS:Successful adenovirus-mediated overexpression of circMYO9A_006 was observed in NMVCs.The increased expression of circMYO9A_006 notably reduced the expres-sion of hypertrophy-related proteins in NMVCs(P<0.01).Concurrently,overexpression of circMYO9A_006 substantially reduced the expression of hypertrophy-associated proteins and diminished the size of PE-induced NRVCs(P<0.05).Dual-luciferase reporter assay identified the activity of 2 IRES in circMYO9A_006.Western blot results indicated that circ-MYO9A_006 could produce the MYO9A-208aa protein with an anticipated molecular weight of 28 kD in NRVCs,primari-ly found in the cytoplasm.Elevated expression of both circMYO9A_006 and MYO9A-208aa consistently reduced the ex-pression of hypertrophy-associated proteins(P<0.01),and counteracted the enlarged size of PE-induced NRVCs(P<0.05).However,increased expression of circMYO9A_006-ATG-mut did not counteract the PE-induced hypertrophic phe-notype of NRVCs.CONCLUSION:circMYO9A_006 attenuates the hypertrophic phenotype of cardiomyocytes by synthe-sizing the MYO9A-208aa protein.

Objective To evaluate the effect of Internet-based psychosocial intervention for primary caregivers of patients with terminal stage cancer.Methods The relevant randomized controlled trials of Internet-based psychosocial intervention for primary caregivers of patients with terminal stage cancer were systematically searched from 10 databases,such as Chinese Biomedical Literature Database,CNKI,PubMed,Embase and CINAHL and etc.The search period was from the establishment to December 18,2023,and 2 investigators screened the literature according to inclusion and exclusion criteria and extracted data.Cochrane Manual 5.1.0 was used to assess the quality of the literature.Meta-analysis was performed using Revman 5.4 software.Results A total of 9 pieces of the literature including 592 primary caregivers were included.Meta-analysis showed that Internet-based psychosocial intervention reduced the level of anxiety and depression for primary caregivers of patients with terminal stage cancer[MD=-1.64,95％CI(-2.68,-0.59),P=0.002]and the burden of care[SMD=-0.39,95％CI(-0.60,-0.18),P＜0.001],and improved quality of life[SMD=0.25,95％CI(0.01,0.48),P=0.040];further research is needed to explore the effect of reducing the level of distress[MD=-0.88,95％CI(-1.91,0.16),P=0.100].Conclusion The Internet-based psychosocial intervention is effective in improving the anxiety,depression and the burden of care of the primary caregivers of patients with terminal stage cancer,and it can improve the quality of life;further research is needed to explore the level of distress reduction.

Objective:To investigate the prevalence and potential classification of symptoms after total knee arthroplasty (TKA) in patients with knee osteoarthritis (KOA), and to analyze the differences in demographic characteristics and surgical data, compare the different potential subgroups, in order to provide a basis for clinical symptom management plans.Methods:This study was a multicenter cross-sectional survey. Through convenience sampling, patients with KOA undergoing TKA in the orthopaedic wards of four tertiary hospitals in Urumqi were selected as the study from November 2023 to February 2024. The study subjects were surveyed using a general information questionnaire, the Visual Analogue Scale (VAS) for pain, the Hospital Anxiety and Depression Scale (HADS), and the Pitts Burgh Sleep Quality Index (PSQI), and the degree of postoperative joint swelling and size of ecchymosis were measured. Latent class analysis was performed using Mplus 8.3 software, and Logistic regression analysis was conducted using SPSS 26.0 software to explore the influencing factors of the latent classes.Results:Totally 337 effective questionnaires were collected, and the recovery rate was 94.7% (337/356), and the age distribution ranged from 47 to 85 (65.19 ± 6.99) years old, with 90 (26.7%) males and 247 (73.3%) females. There were 92.3% (311/337) of TKA patients with postoperative symptom cluster. The symptom cluster of patients with TKA were identified as 3 classes. They were named as "high level pain-psychological disorder group"(12.5%, 39/311), "high bruises-moderate psychological disorders group"(25.4%, 79/311) and "low symptom burden group" (62.1%, 193/311). The results of the unordered multi-class logistic regression analysis showed that age 45-59 years ( OR = 2.367), body mass index 24.0-27.9 kg/m 2 ( OR = 0.207), living with children/parents ( OR = 6.473), and this being the second joint surgery ( OR = 0.040) were the factors influencing the "high level pain-psychological disorders group" (all P<0.05). The factors influencing the "high bruises-moderate psychological disorders group" were living with children/parents ( OR = 4.023), comorbid chronic diseases ( OR = 1.979, 3.842), and intraoperative blood loss ≤100 ml ( OR = 2.342) (all P<0.05). Conclusions:The postoperative symptom cluster of TKA patients have a relatively high incidence, and there is heterogeneity within the symptom cluster, so nurses need to identify at-risk patients early according to the characteristics of different categories and give interventions.