Intervertebral disc degeneration (IDD) is largely attributed to impaired endogenous repair. Nucleus pulposus-derived stem cells (NPSCs) senescence leads to endogenous repair failure. Small extracellular vesicles/exosomes derived from mesenchymal stem cells (mExo) have shown great therapeutic potential in IDD, while whether mExo could alleviate NPSCs senescence and its mechanisms remained unknown. We established a compression-induced NPSCs senescence model and rat IDD models to evaluate the therapeutic efficiency of mExo and investigate the mechanisms. We found that mExo significantly alleviated NPSCs senescence and promoted disc regeneration while knocking down thioredoxin (TXN) impaired the protective effects of mExo. TXN was bound to various endosomal sorting complex required for transport (ESCRT) proteins. Autocrine motility factor receptor (AMFR) mediated TXN K63 ubiquitination to promote the binding of TXN on ESCRT proteins and sorting of TXN into mExo. Knocking down exosomal TXN inhibited the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2) and activator protein 1 (AP-1). NRF2 and AP-1 inhibition reduced endogenous TXN production that was promoted by exosomal TXN. Inhibition of NRF2 in vivo diminished the anti-senescence and regenerative effects of mExo. Conclusively, AMFR-mediated TXN ubiquitination promoted the sorting of TXN into mExo, allowing exosomal TXN to promote endogenous TXN production in NPSCs via TXN/NRF2/AP-1 feed-forward circuit to alleviate NPSCs senescence and disc degeneration.

Lacticaseibacillus rhamnosus GG is one of the most studied probiotic strains，characterized by high acid resistance，high bile salt resistance，and strong adhesion.The main functions of Lacticaseibacillus rhamnosus GG include enhancing intestinal barrier function，inhibiting pathogen adhesion，regulating the body's immune system，which make it effective in treating and preventing gastrointestinal diseases in children and adults.This article reviewes the application research progress of Lacticaseibacillus rhamnosus GG in the treatment of common pediatric digestive system diseases such as necrotizing enterocolitis，infantile colic，non-alcoholic fatty liver disease，inflammatory bowel disease，antibiotic associated diarrhea，irritable bowel syndrome，and acute gastroenteritis in children.

Objectives:To construct a multi-segment cervical spinal stenosis with instability model through finite element technology,and to analyze and compare the stability difference of posterior open door laminoplasty combined with unilateral or bilateral lateral mass screw fixations.Methods:A C0-T1 muscular finite element model of the cervical spine was constructed based on the cervical computed tomography(CT)data of an adult healthy male volunteer who visited Ningbo No.6 Hospital in January 2023.The model's range of motion(ROM)in flexion and extension,lateral bending,and rotation aligned closely with the ROM re-sults reported in relevant literature,showing reasonable stress distribution and high reliability.And based on the complete model,models of cervical multi-segment spinal stenosis and multi-segment spinal stenosis com-bined with instability were generated using finite element technology.After setting the left side of the two models as the door opening side,removing the full layer of vertebral lamina and fixing with titanium plate,and making a V-shaped groove on the right side as the door axis,an open-door model of multi-segment spinal stenosis(classical open-door group)and an open-door model of multi-segment spinal stenosis combined with instability(unstable open-door group)were established,respectively.On the basis of model of unstable open-door group,unilateral or bilateral lateral mass screws were implanted in C3-C7 segments,generating a unilateral lateral mass screw fixation model(unilateral screw group)and a bilateral lateral mass screw fixation model(bilateral screw group).The ROM and stress distribution in flexion extension,lateral bending,and rotation directions of each group of models were calculated.The ROM results of the unstable open-door group,unilateral screw group,and bilateral screw group were tested using independent sample F,and comparison between groups was made with SNK's q test.Results:The ROMs in all motion directions of the C3-C7 segment in unilateral screw group and bilateral screw group were smaller than unstable open-door group(P＜0.05);The ROMs in flexion,extension,and lateral bending directions at the C3-C7 segments in the bilateral screw group was also smaller than those in the unilateral screw group(P＜0.05).The peak stress of the screws in the unilateral screw group was relatively high in the left bending and left rotation directions,with values of 402.9MPa and 450.2MPa,respectively;In the bilateral screw group,the stress peaks of the screw in flexion and extension directions were significantly higher than those in the other directions,at 409.8MPa and 651 MPa,respectively.Conclusions:Compared to the open door extended laminoplasty,both unilateral lateral mass screw fixation and bilateral lateral mass screw fixation demonstrate good mechanical stability.

Objective:To investigate the role and molecular mechanism of sensory neuron-derived exosomes (nExo) in mediating intervertebral disc degeneration (IDD).Methods:A rat IDD model was constructed, with nExo injected into the intervertebral disc. After 4 weeks, the degenerative grades of operated discs were evaluated using histological staining, while the senescent phenotype of nucleus pulposus stem cells (NPSC) in the tissue was evaluated using immunofluorescence staining. For in vitro experiments, 24 hours after the treatment of nExo to NPSC, immunoblotting, flow cytometry, or senescence-associated β-galactosidase staining was applied to evaluate the senescent phenotype of NPSC. Transcriptomics analysis was applied to identify the key molecules that mediate nExo-induced cells senescence. After 4 weeks of injecting nExo and TXN into the rat tail disc degeneration model.Results:nExo increased the degenerative grades of IDD and increased the proportion of TEK +p16 + and TEK +p21 + cells (from 36.32% ±4.04%, 33.69% ±4.56% in IDD group to 56.41% ±5.26%, 50.14% ±8.49% in IDD+nExo group, respectively; t=7.420, P<0.001; t=4.184, P<0.0019, respectively) in the disc tissue. Besides, nExo promoted the expression of p16 and p21 in NPSC and increased the percentage of cells with positive senescence-associated β-galactosidase staining (from 7.32%±1.73% to 58.22%±11.38%, t=7.658, P=0.002), while the percentage of G2/M cells was downregulated (from 18.10%±1.32% to 1.60%±0.67%, t=19.290, P<0.001). Transcriptomic analysis showed that the differential genes of CTRL vs. nExo were closely related to cell senescence, and TXN was screened by intersecting the differential gene set with the cellular senescence gene sets from the published database. Furthermore, we verified that nExo decreased the content of TXN in NPSC, while exogenous TXN downregulated the expression of p16 and p21 in NPSC, reduced the positive cell rate of senescence-associated β-galactosidase staining (from 58.84%±3.99% to 21.68%±8.16%, t=7.048, P=0.021), increased the percentage of G2/M cells (from 1.21%±0.34% to 15.26%±2.60%, t=9.259, P=0.001). TXN significantly reduced the grade of disc tissue degeneration (histological score: 14.33±0.82 in the nExo group; 8.17±1.17 in the nExo+TXN group, t=10.590, P<0.001), significantly increased the content of extracellular matrix (from 10.94±4.35 μg/mg to 50.55±12.16 μg/mg, t=7.512, P<0.001), and reduced the proportion of TEK +p16 + and TEK +p21 + double-positive cells (from 54.92%±4.21% and 60.31%±9.02% to 27.93%±3.26% and 33.75%±8.07%, respectively; t=12.430, P<0.001; t=5.375, P<0.001, respectively). Conclusion:nExo promotes cell senescence and IDD by downregulating TXN in NPSC.

Encephalomyocarditis virus (EMCV) is a non-enveloped, positive-sense, single-stranded RNA virus that belongs to the family Picornaviridae and the genus Cardiovirus. EMCV has the ability to infect various mammals, such as mice, pigs, and cattle. In addition, humans are susceptible to EMCV infection, and the seropositivity rate of relevant antibodies in healthy populations is steadily increasing, which poses a potential risk of epidemics. The initial step of viral infection in cells involves recognition and attachment to cell surface receptors, followed by endocytosis into the cells. Subsequently, viral proteins interact with host proteins within the cells to promote their own replication. With the progress made in protein-protein interaction studies and the development of high-throughput sequencing technologies, multiple host proteins that interact with EMCV have been identified. This article summarizes the host proteins that interact with EMCV during infection, explores the mechanisms by which these proteins facilitate or inhibit viral invasion, discusses the latest progress in EMCV-induced endocytosis and intracellular signaling, hoping to provide reference for better elucidating EMCV receptor proteins, understanding viral infection and replication mechanisms, studying virus-host interactions and tissue tropism, and developing novel targeted antiviral drugs and prevention strategies.

Objective To present the initial practice of a novel procedure for the surgical treatment of inguinal hernia-"lateral approach single-incision laparoscopic totally extraperitoneal(L-SILTEP)repair"in certain specific situations.Methods The clinical data of 110 inguinal hernia patients who underwent L-SILTEP in the First Affiliated Hospital of Ningbo University,Shanghai General Hospital affiliated to Shanghai Jiao Tong University School of Medicine,and Shanghai East Hospital affiliated to Tongji University from June 2021 to March 2024 were collected retrospectively.Patients' demographics,surgical details,length of hospital stay,and postoperative outcomes were analyzed respectively.Results All surgeries were completed successfully and there was no conversion.The median surgical time was 55(41.25,70)mins and the intraoperative blood loss was 5(2,10)mL.In surgery,inferior epigastric artery injury occurred in 5 cases(4.5%)and spermatic cord injury occurred in 1 case(0.9%).The mean visual analog scale(VAS)scores pain assessment at 6,24,and 48 h after surgery were 3.0±0.8,1.9±0.7 and 1.1±0.4,respectively.The duration of hospital stay was(3.3±0.7)days.The most common postoperative complication was seroma,which occurred in 9 cases(8.2%).Additionally,extraperitoneal hematoma occurred in 1 case(0.9%)and scrotum effusion in 1 case(0.9%).Conclusions Generally,L-SILTEP is safe,feasible and effective.However,due to its advanced technique-demand,the application of L-SILTEP should be patient-specific and surgeon-specific.The successful implementation of this surgical procedure necessitates extensive training and meticulous attention to the surgical details.

Objective To find out the prevalence of antiretroviral therapy(ART)drugs among treponema pallidum(TP)antibody(anti-TP)positive blood donors in Shenzhen,and to assess the blood safety risks brought about by the new trends of human immunodeficiency virus(HIV)diagnosis and treatment.Methods A stratified random sampling method was used to select 60 repeat blood donors(negative control group)who passed blood screening in Shenzhen from March 2019 to January 2023,and 3 people who regularly took known ART drugs were named positive control group,358 anti-TP positive/anti-HIV negative blood do-nors were named experimental group 1,20 anti-TP positive/anti-HIV positive blood donors were named ex-perimental group 2.The liquid chromatography-mass spectrometry(HPLC-MS/MS)was applied to detect the concentration of 8 ART drugs in plasma samples of each group,and the use of ART drugs was analyzed.Re-sults After the positive control group's plasma was diluted with a 1:6 dilution mixture,the ART drugs could still be detected.The positive mixed plasma samples of 1:6 people in Group 1 and Group 2 were split and validation,one ART drug positive sample was detected in Group 2,which was positive for anti-HIV,pro-tein immunoblotting,and HIV RNA.The detection rate of ART drugs in anti-TP positive blood donors was 0.26％,0.00％in Group 1 and 4.00％in Group 2.Conclusion The use of ART drugs has been found among anti-TP positive blood donors in Shenzhen,and people with HIV infection and high-risk sexual behavior are more likely to use antiretroviral drugs.

The upset insomnia caused by life and work pressure has seriously affected the physical and mental health of modern people and induced many diseases. The quality of Chinese medicine for nourishing heart and tranquilizing mind is stable, and it has a significant effect on the treatment of insomnia, with fewer adverse reactions, and no dependence on sedative and hypnotic as chemical drugs. The Chinese herbal pieces and preparations for nourishing heart and tranquilizing mind can be divided into psychotropic and sedative drugs according to their functions. Their active ingredients mainly include flavonoids, alkaloids, organic acids, polysaccharides, amino acids and vitamins, etc. They are mostly used in the treatment of cardiovascular diseases and central nervous system inhibition. In this paper, the types and active ingredients and development tendency and application status of the Chinese herbal pieces and preparations of nourishing heart and tranquilizing mind were reviewed individually, in order to provide reference for the development of drugs of nourishing heart and tranquilizing mind in the field of clinical application and related drugs.

【Objective】 To explore the the potential risks of antiretroviral therapy(ART) drugs on blood safety among blood donors in Shenzhen. 【Methods】 High pressure liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was used to measure ART drugs concentrations in the plasma of regular blood donors (negative control group, n=86) and anti-HIV positive individuals (experimental group, n=98, detected from approximately 440 000 blood donors during 2019—2023). The baseline plasma concentrations of ART drugs in the negative control group were clarified, and the impact of ART drugs on blood safety was analyzed. 【Results】 The baseline concentrations of ART drugs were not detected in 86 samples of negative control group. Four positive ART drugs samples were detected in 1∶2 pooled plasma samples of 98 anti-HIV positive blood donors plasma in the resolution test. The ART positive rate of anti-HIV positive donors was 4.08%, with tenofovir, lamivudine and efavirenz detected in three blood donors and lamivudine, lopinavir, ritonavir and zidovudine detected in one blood donor. 【Conclusion】 ART drugs were found among anti-HIV positive blood donors in Shenzhen. Additional research is needed to investigate the motivation of these specific donors, so as to ascertain the groups most susceptible to potential risks, and guarantee blood safety.

Objectives:To construct a multi-segment cervical spinal stenosis with instability model through finite element technology,and to analyze and compare the stability difference of posterior open door laminoplasty combined with unilateral or bilateral lateral mass screw fixations.Methods:A C0-T1 muscular finite element model of the cervical spine was constructed based on the cervical computed tomography(CT)data of an adult healthy male volunteer who visited Ningbo No.6 Hospital in January 2023.The model's range of motion(ROM)in flexion and extension,lateral bending,and rotation aligned closely with the ROM re-sults reported in relevant literature,showing reasonable stress distribution and high reliability.And based on the complete model,models of cervical multi-segment spinal stenosis and multi-segment spinal stenosis com-bined with instability were generated using finite element technology.After setting the left side of the two models as the door opening side,removing the full layer of vertebral lamina and fixing with titanium plate,and making a V-shaped groove on the right side as the door axis,an open-door model of multi-segment spinal stenosis(classical open-door group)and an open-door model of multi-segment spinal stenosis combined with instability(unstable open-door group)were established,respectively.On the basis of model of unstable open-door group,unilateral or bilateral lateral mass screws were implanted in C3-C7 segments,generating a unilateral lateral mass screw fixation model(unilateral screw group)and a bilateral lateral mass screw fixation model(bilateral screw group).The ROM and stress distribution in flexion extension,lateral bending,and rotation directions of each group of models were calculated.The ROM results of the unstable open-door group,unilateral screw group,and bilateral screw group were tested using independent sample F,and comparison between groups was made with SNK's q test.Results:The ROMs in all motion directions of the C3-C7 segment in unilateral screw group and bilateral screw group were smaller than unstable open-door group(P＜0.05);The ROMs in flexion,extension,and lateral bending directions at the C3-C7 segments in the bilateral screw group was also smaller than those in the unilateral screw group(P＜0.05).The peak stress of the screws in the unilateral screw group was relatively high in the left bending and left rotation directions,with values of 402.9MPa and 450.2MPa,respectively;In the bilateral screw group,the stress peaks of the screw in flexion and extension directions were significantly higher than those in the other directions,at 409.8MPa and 651 MPa,respectively.Conclusions:Compared to the open door extended laminoplasty,both unilateral lateral mass screw fixation and bilateral lateral mass screw fixation demonstrate good mechanical stability.