In recent years, the development of host-acting antibacterial compounds has gradually become a hotspot in the field of anti-infection. Through research on the interaction mechanism between hosts and pathogenic bacteria, it has been found that the immune system is one of the key targets of host-acting antibacterial compounds. There is a communication system called the quorum sensing system in microorganisms, which mainly adjusts the structure of multi-microbial community and coordinates the group behavior. When the quorum sensing molecules secreted by microorganisms reach a threshold concentration, the quorum sensing system is activated and the overall gene expression of the microorganism is changed. In addition to regulating the density of microorganisms, quorum sensing molecules can also act as a link between pathogenic microorganisms and hosts, entering the host immune system and playing a role in affecting the morphological structure of immune cells, secreting cytokines, and inducing apoptosis, leading to host immune injury and causing host immune dysfunction.The key mechanism of 3-oxo-C12-HSL and other acyl-homoserine lactone (AHL) molecules in the innate immune system has been extensively studied. The lipid solubility allows AHLs to pass through the plasma membrane of host immune cells easily and induce dissolution of lipid domains. Then, it acts through signaling pathways such as p38MAPK and JAK-STAT, further influencing the immune cell’s defense response to bacteria and potentially leading to cell apoptosis. Additionally, the human lactonase paraoxonase 2, which can degrade3-oxo-C12-HSL, has been found in macrophage. It acts as an immune regulator that promotes macrophage phagocytosis of pathogens and is hypothesized to have the ability to reduce bacterial resistance. The mechanism of quorum sensing molecules in the adaptive immune system is less studied, the current results suggest that 3-oxo-C12-HSL is closely related to the mitochondrial pathway in host immune cells. For example, 3-oxo-C12-HSL induces apoptosis of Jurkat cells by inhibiting the expression of three mitochondrial electron transport chain proteins; it can also trigger mitochondrial dysfunction and induce mast cell apoptosis through Ca²⁺ signaling.Among the quorum sensing molecules, the AHLs have the greatest impact on plant immune system. The different effects on plant resistance depends on the chain lengths of acyl groups in bacterial-produced AHLs. Short-chain AHLs (C4-HSL and C8-HSL) induce plant resistance to pathogenic bacteria mainly through the auxin pathway and jasmonic acid pathway. Long-chain AHL (3-oxo-C14-HSL) is commonly used in hosts against fungal pathogens by inducing stomata defense responses, and the reaction process is related to salicylic acid. Diffusible signal factor molecules also interfere with the stomatal immunity caused by pathogens. It may act through the formin nanoclustering-mediated actin assembly and MPK3 pathway to inhibit the innate immunity of Arabidopsis. In summary, AHLs induced different plant pathways and affects the plant-bacteria interactions to trigger plant immunity. As a quorum sensing molecule of fungi, farnesol has similar effects on host immunity as AHLs, such as stimulating cytokine secretion and activating an inflammatory response. It also plays a unique role on dendritic cell differentiation and maturation. In addition, studies have found that farnesol has a protective effect on autoimmune encephalomyelitis, which may be related to its effect on the composition of intestinal microorganisms of the host.Therefore, targeting the host immune system and quorum sensing molecules to develop antibacterial compounds can effectively inhibit the invasion of pathogens and subserve the host to resist the influence of pathogenic bacteria. This article will review the mechanism of host immune responses triggered by important quorum sensing molecules, aiming to explore the targets of host-acting antibacterial compounds and provide new directions for the prevention or treatment of causative infectious sources and the development of related drugs.

With the increasing application of immune checkpoint inhibitors(ICI)in anti-tumor therapy,ICI related infections are often neglected.Mycobacterium tuberculosis(MTB)is also a common pathogen.We reported a case of ICI related pulmonary tuberculosis from Zhongshan Hospital,Fudan University.Meanwhile,18 cases of ICI related tuberculosis infection were collected through literature search,and the characteristics of ICI related tuberculosis were analyzed to improve the understanding in clinic practice.All the cases were confirmed TB including 15 cases of pulmonary tuberculosis(1 case with complication of intestinal tuberculosis)and 4 cases of extra-pulmonary tuberculosis(1 case of disseminated tuberculosis,bone tuberculosis,tuberculous pericarditis and tuberculous pleurisy,respectively).The chest CT characteristics of pulmonary tuberculosis mainly included centrilobular nodules,ground glass nodules,empty lesions,patchy shadows,consolidation and large infiltration.Eighteen cases started anti-tuberculosis treatment,while 4 cases continued ICI treatment.Three cases suspended ICI(2 cases had remission after reuse)and 11 cases stopped ICI,and 1 case was not mentioned.ICI related tuberculosis may be a direct complication of tumor immunotherapy.It is necessary to screen tuberculosis infection and exclude active tuberculosis before immunotherapy.If there are suspected symptoms such as fever,cough and sputum during ICI treatment,active tuberculosis should be taken into account.

Objective To construct a risk prediction score model for serious adverse event (SAE) after cardiac catheterization in patients with adult congenital heart disease (ACHD) and pulmonary hypertension (PH) and verify its predictive effect. Methods The patients with PH who underwent cardiac catheterization in Wuhan Asian Heart Hospital Affiliated to Wuhan University of Science and Technology from January 2018 to January 2022 were retrospectively collected. The patients were randomly divided into a model group and a validation group according to the order of admission. The model group was divided into a SAE group and a non-SAE group according to whether SAE occurred after the catheterization. The data of the two groups were compared, and the risk prediction score model was established according to the results of multivariate logistic regression analysis. The discrimination and calibration of the model were evaluated using the area under the receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow test, respectively. Results A total of 758 patients were enrolled, including 240 (31.7%) males and 518 (68.3%) females, with a mean age of 43.1 (18.0-81.0) years. There were 530 patients in the model group (47 patients in the SAE group and 483 patients in the non-SAE group) and 228 patients in the validation group. Univariate analysis showed statistical differences in age, smoking history, valvular disease history, heart failure history, N-terminal pro-B-type natriuretic peptide, and other factors between the SAE and non-SAE groups (P<0.05). Multivariate analysis showed that age≥50 years, history of heart failure, moderate to severe congenital heart disease, moderate to severe PH, cardiac catheterization and treatment, surgical general anesthesia, and N-terminal pro-B-type natriuretic peptide≥126.65 pg/mL were risk factors for SAE after cardiac catheterization for ACHD-PH patients (P<0.05). The risk prediction score model had a total score of 0-139 points and patients who had a score>50 points were high-risk patients. Model validation results showed an area under the ROC curve of 0.937 (95%CI 0.897-0.976). Hosmer-Lemeshow goodness-of-fit test: χ2=3.847, P=0.797. Conclusion Age≥50 years, history of heart failure, moderate to severe congenital heart disease, moderate to severe PH, cardiac catheterization and treatment, general anesthesia for surgery, and N-terminal pro-B-type natriuretic peptide≥126.65 pg/mL were risk factors for SAE after cardiac catheterization for ACHD-PH patients. The risk prediction model based on these factors has a high predictive value and can be applied to the risk assessment of SAE after interventional therapy in ACHD-PH patients to help clinicians perform early intervention.

ObjectiveIn recent years, with the intensification of environmental issues and the depletion of ozone layer, incidence of skin tumors has also significantly increased, becoming one of the major threats to people’s lives and health. However, due to factors such as high concealment in the early stage of skin tumors, unclear symptoms, and large human skin area, most cases are detected in the middle to late stage. Early detection plays a crucial role in postoperative survival of skin tumors, which can significantly improve the treatment and survival rates of patients. We proposed a rapid non-invasive electrical impedance detection method for early screening of skin tumors based on bioimpedance spectroscopy (BIS) technology. MethodsFirstly, we have established a complete skin stratification model, including stratum corneum, epidermis, dermis, and subcutaneous tissue. And the numerical analysis method was used to investigate the effect of dehydrated and dry skin stratum corneum on contact impedance in BIS measurement. Secondly, differentiation effect of different diameter skin tumor tissues was studied using a skin model after removing the stratum corneum. Then, in order to demonstrate that BIS technology can be used for detecting the microinvasion stage of skin tumors, we conducted a simulation study on the differentiation effect of skin tumors under different infiltration depths. Finally, in order to verify that the designed BIS detection system can distinguish between tumor microinvasion periods, we conducted tumor invasion experiments using hydrogel treated pig skin tissue. ResultsThe simulation results show that a dry and high impedance stratum corneum will bring about huge contact impedance, which will lead to larger measurement errors and affect the accuracy of measurement results. We extracted the core evaluation parameter of relaxed imaginary impedance (Z_imag-relax) from the simulation results of the skin tumor model. When the tumor radius (R_tumor) and invasion depth (h)>1.5 mm, the designed BIS detection system can distinguish between tumor tissue and normal tissue. At the same time, in order to evaluate the degree of canceration in skin tissue, the degree of tissue lesion (ε_worse) is defined by the relaxed imaginary impedance (Z_imag-relax) of normal and tumor tissue (ε_worse is the percentage change in virtual impedance of tumor tissue relative to that of normal tissue), and we fitted a Depth-Z_imag-relax curve using relaxation imaginary impedance data at different infiltration depths, which can be applied to quickly determine the infiltration depth of skin tumors after being supplemented with a large amount of clinical data in the future. The experimental results proved that when ε_worse=0.492 0, BIS could identify microinvasive tumor tissue, and the fitting curve correction coefficient of determination was 0.946 8, with good fitting effect. The simulation using pig skin tissue correlated the results of real human skin simulation with the experimental results of pig skin tissue, proving the reliability of this study, and laying the foundation for further clinical research in the future. ConclusionOur proposed BIS method has the advantages of fast, real-time, and non-invasive detection, as well as high sensitivity to skin tumors, which can be identified during the stage of tumor microinvasion.

Aim To explore the effects of Lycium berry seed oil on Nrf2/ARE pathway and oxidative damage in testis of subacute aging rats. Methods Fifty out of 60 male SD rats, aged 8 weeks, were subcutaneously injected with 125 mg • kg"D-galactosidase in the neck for 8 weeks to establish a subacute senescent rat model. The presence of senescent cells was observed using P-galactosidase ((3-gal), while testicular morphology was examined using HE staining. Serum levels of testosterone (testosterone, T), follicle-stimulating hormone ( follicle stimulating hormone, FSH ) , luteinizing hormone ( luteinizing hormone, LH ) , superoxide dis-mutase ( superoxide dismutase, SOD ) , glutathione ( glutathione, GSH) and malondialdehyde ( malondial-dehyde, MDA) were measured through ELISA, and the expressions of factors related to aging, oxidative damage, and the Nrf2/ARE pathway were assessed via immunohistochemical analysis and Western blotting. Results After successfully identifying the model, the morphology of the testis was improved and the intervention of Lycium seed oil led to a down-regulation in the expression of [3-gal and -yH2AX. The serum levels of SOD, GSH, T, and FSH increased while MDA and LH decreased (P 0. 05) . Additionally, there was an up-regulated expression of Nrf2, GCLC, NQOl, and SOD2 proteins in testicular tissue ( P 0. 05 ) and nuclear expression of Nrf2 in sertoli cells. Conclusion Lycium barbarum seed oil may reduce oxidative damage in testes of subacute senescent rats by activating the Nrf2/ARE signaling pathway.

Objective To understand the growth and development status and differences between small for gestational age(SGA)and appropriate for gestational age(AGA)preterm infants during corrected ages 0-24 months,and to provide a basis for early health interventions for preterm infants.Methods A retrospective study was conducted,selecting 824 preterm infants who received regular health care at the Guangzhou Women and Children's Medical Center from July 2019 to July 2022,including 144 SGA and 680 AGA infants.The growth data of SGA and AGA groups at birth and corrected ages 0-24 months were analyzed and compared.Results The SGA group had significantly lower weight and length than the AGA group at corrected ages 0-18 months(P<0.05),while there were no significant differences between the two groups at corrected age 24 months(P>0.05).At corrected age 24 months,85%(34/40)of SGA and 79%(74/94)of AGA preterm infants achieved catch-up growth.Stratified analysis by gestational age showed that there were significant differences in weight and length at corrected ages 0-9 months between the SGA subgroup with gestational age<34 weeks and the AGA subgroups with gestational age<34 weeks and≥34 weeks(P<0.05).In addition,the weight and length of the SGA subgroup with gestational age≥34 weeks showed significant differences compared to the AGA subgroups with gestational age<34 weeks and≥34 weeks at corrected ages 0-18 months and corrected ages 0-12 months,respectively(P<0.05).Catch-up growth for SGA infants with gestational age<34 weeks and≥34 weeks mainly occurred at corrected ages 0-12 months and corrected ages 0-18 months,respectively.Conclusions SGA infants exhibit delayed early-life physical growth compared to AGA infants,but can achieve a higher proportion of catch-up growth by corrected age 24 months than AGA infants.Catch-up growth can be achieved earlier in SGA infants with a gestational age of<34 weeks compared to those with≥34 weeks.

Objective To analyze the prognostic significance and biological effects of cytochrome P450 family 27 subfamily A member 1(CYP27A1)in hepatocellular carcinoma(HCC),and to preliminarily explore its molecular mechanism of regulating the malignant growth of HCC.Methods The Cance Genome Atlas(TCGA)database was used to analyze the expression level of CYP27A1 and its prognostic effect on HCC patients.The samples were divided into CYP27A1 high-expression group(n=170)and low-expression group(n=170)based on the median expression of CYP27A1 in HCC,gene set enrichment analysis(GSEA)was performed to investigate gene sets associated with CYP27A1 expression.The subcellular localization of CYP27A1 was detected by immunofluorescence staining and search database.The over-expression plasmid of CYP27A1 was constructed and then transfected into the HCC cells MHCC-97H and HCCLM3 cell lines,including two groups,namely control group(transfecting empty vector)and CYP27A1 over-expression group(transfecting CYP27A1 over-expressed vector).CCK-8,flow cytometer,and reactive oxygen species(ROS)fluorescence probe were applied to detect the effects of CYP27A1 over-expression on cell viability,apoptosis and ROS levels in HCC cells.Combining bioinformatics to analyze the correlation between CYP27A1 and the expression of ROS generation-related genes and HCC proliferation-related genes.Results Compared with the normal liver tissue,the expression level of CYP27A1 mRNA in HCC tissue was significantly reduced(P<0.01).The expression of CYP27A1 was significantly correlated with sex,T stage,tumor grade and tumor stage of HCC patients(P<0.05).Compared to the CYP27A1 high-expression group,patients in CYP27A1 low-expression group had lower survival rate(P<0.01).GSEA enrichment analysis revealed that the levels of HCC stem cell-related gene clusters and HCC proliferation gene clusters were remarkably increased in CYP27A1 low-expression group.The immunofluorescence showed that CYP27A1 was mainly located in nucleus in MHCC-97H and HCCLM3,whereas CYP27A1 was mainly located in mitochondria in HepG2.CYP27A1 over-expression attenuated cell viability(P<0.01),and reduced the ROS levels(P<0.05),whereas it had no effects on the apoptosis in HCC cells(P>0.05).The expression of CYP27A1 and the expression of inhibiting ROS generation-related genes were positively correlated(P<0.05),while the expression of inhibiting ROS generation-related genes and the expression of HCC proliferation-related genes were negatively correlated(P<0.05).Conclusions The expression of CYP27A1 was decreased in HCC,and down-regulated CYP27A1 promoted cell growth by enhancing ROS generation,although the precise mechanism requires future educidation.

Objective To investigate the clinical manifestations,molecular genetics and gonadal pathol-ogy characteristics of patients with disorders of sex development(DSD),and to summarize the clinical experi-ence of identifying rare diseases from common symptoms.Methods The clinical data of 416 patients with DSD diagnosed and treated in the multidisciplinary center of DSD of Guangzhou Women and Children's Medical Cen-ter from May 2018 to August 2023 were retrospectively analyzed,summarized and discussed.Results Accord-ing to chromosome karyotype,416 cases of DSD were classified into three types:92 cases(22.1％)of abnormal sex chromosome karyotype,285 cases(68.5％)of 46,XY karyotype and 39 cases(9.4％)of 46,XX karyotype.Among the 92 patients with abnormal sex chromosome karyotype,59 cases were raised as males,18 cases(30.5％)complained of short penis with hypospadias and cryptorchidism.The most common karyotype was 45,X/46,XY(58 cases,63.0％).Among the 285 patients with 46,XY karyotype,238 cases were raised as males,and 63 cases(26.5％)complained of short penis and hypospadias;47 cases were raised as females,and 13 ca-ses(27.7％)complained of inguinal mass.A total of 216 patients with 46,XY karyotype were subjected to whole exome gene detection,and 155 cases(71.8％)were found to have molecular pathogenesis with the clinical phe-notype.Among the 39 patients with 46,XX karyotype,19 cases were raised as males,and 8 cases(42.1％)com-plained of short penis and hypospadias.In the 18 cases of gonad biopsy,17 cases showed testicular tissue in go-nads.Whole exome sequencing was performed in 14 cases.NR5A1 gene heterozygous mutation,SRY gene muta-tion and SOX3 gene mutation were found in 2 cases,respectively(14.3％).Twenty cases were raised as females,and 14 cases(70.0％)complained of clitoral hypertrophy.Gonad biopsy was performed in 8 cases,with 7 cases of ovotestis(87.5％)and 1 case of NR5A1 gene heterozygous mutation(14.3％).Conclusions The etiologies of DSD are complex and diverse,and the clinical manifestations are various,which can be manifested as hypospa-dias,micropenis,cryptorchidism and other common symptoms of the urinary system.Different etiologies have dif-ferent treatment options.Therefore,chromosome karyotype,molecular genetic testing and gonadal pathology can be used to clarify the cause of disease,especially for rare diseases,improve the detection rate,reduce the rate of missed diagnosis,and ensure reasonable treatment,especially sex selection.

Objective This study proposes a chairside digital design and manufacturing method for band and loop space maintainers and preliminarily validates its clinical feasibility.Methods Clinical cases of 10 children requiring space maintenance caused by premature loss of primary teeth were collected.Intraoral scan data of the affected children were also collected to establish digital models of the missing teeth.Using a pediatric band and loop space maintainer de-sign software developed by our research team,a rapid personalized design of band and loop structures was achieved,and a digital model of an integrated band and loop space maintainer was ultimately generated.A chairside space maintainer was manufactured through metal computer numerical control machining for the experimental group,whereas metal 3D printing in the dental laboratory was used for the control group.A model fitting assessment was conducted for the space maintainers of both groups,and senior pediatric dental experts were invited to evaluate the clinical feasibility of the space maintainers with regard to fit and stability using the visual analogue scale scoring system.Statistical analysis was also performed.Results The time spent in designing and manufacturing the 10 space maintainers of the experimental group was all less than 1 h.Statistical analysis of expert ratings showed that the experimental group outperformed the control group with regard to fit and stability.Both types of space maintainers met clinical requirements.Conclusion The chairside digital design and manufacturing method for pediatric band and loop space maintainers proposed in this study can achieve same-day fitting of space maintainers at the first appointment,demonstrating good clinical feasibility and significant potential for clinical application.

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.