Antibody-drug conjugates （ADCs） are a novel class of anti-tumor agents composed of a targeted monoclonal antibody， a cytotoxic drug， and a linker connecting the two. They combine the high specificity of antibodies with the potent cytotoxicity of chemotherapeutic agents. Triple-negative breast cancer （TNBC） is characterized by high aggressiveness， elevated risks of recurrence and metastasis， and poor prognosis， largely due to the lack of effective therapeutic targets. This review summarizes the research progress of ADCs in the treatment of TNBC. It has been found that ADCs targeting human epidermal growth factor receptor 2 （such as trastuzumab deruxtecan）， trophoblast cell surface antigen 2 （such as sacituzumab govitecan and datopotamab deruxtecan）， zinc transporter LIV-1 （such as ladiratuzumab vedotin）， HER-3 （such as patritumab deruxtecan）， epidermal growth factor receptor （such as AVID100）， and glycoprotein non-metastatic melanoma protein B （such as glembatumumab vedotin） have all demonstrated promising therapeutic effects against TNBC. Despite challenges including acquired resistance and treatment-related toxicities， ADCs are undoubtedly reshaping the therapeutic landscape for TNBC and are expected to occupy a more central position in TNBC treatment in the future.

Purpose To investigate the sex differences of white matter damage in Alzheimer's disease(AD)and their association with cognitive impairment.Materials and Methods This retrospective study included 88 AD patients(48 females),71 amnestic mild cognitive impairment(aMCI)patients(39 females),and 95 healthy controls(63 females)recruited from the Memory Disorder Clinic at the First Affiliated Hospital of Anhui Medical University from September 2017 to July 2024.High-resolution three-dimensional T1 structure images and diffusion tensor imaging images were all obtained from each participant.The mean diffusivity(MD)and fractional anisotropy(FA)values of each white matter region were obtained,and the two-way ANOVA analysis was conducted to investigate brain regions with interaction effects between groups and sexes,those brain regions were then chosen as regions of interest for further correlation analysis with a series of cognitive scale scores.Results In terms of FA values,the right posterior corona radiata,right anterior limb of the internal capsule and left corticospinal tract showed interaction between sexes and cognitive groups(F=4.764,3.812,5.937,all P<0.05).The FA value of AD group was significantly lower than that of healthy control and aMCI group(all P<0.05),but there was no significant difference between healthy control and aMCI group(except the right anterior limb of the internal capsule,P=0.018).In AD group,FA values were significantly higher in women than in men in the previously described brain regions(all P<0.05),while there was no significant difference in FA values between male and female in healthy control and aMCI groups(except the left corticospinal tract,P<0.001).In terms of MD values,the right anterior limb of the internal capsule,right superior corona radiata and left external capsule showed interaction effect between sexes and cognitive groups(F=8.581,3.680,7.218,all P<0.05).The MD value of AD group was significantly higher than that of aMCI group(P<0.001),and aMCI group was higher than that of healthy control group(all P<0.05).In AD group,the MD values in the above brain regions were significantly higher in males than those in females(all P<0.01),while no significant difference was found between males and females in healthy control and aMCI groups(except for the left external capsule,P<0.05).For correlation analysis,the AD group was dimidiated into two groups by sex,the scores of the Montreal cognitive assessment,the Mini Mental state examination and the verbal fluency test of the female patient group were positively correlated with the FA values of the right posterior corona radiate(r=0.372,P=0.009;r=0.345,P=0.016;r=0.383,P=0.007),while the Mini Mental state examination and the verbal fluency test scores of female AD patient group were negatively correlated with the MD values of the right superior corona radiata(r=-0.360,P=0.012;r=-0.360,P=0.003).Conclusion Compared to the healthy control and MCI groups,white matter damage in AD patients shows sex differences and is associated with general cognitive and language functions impairment in female AD patients.

ObjectiveTo perform a genome-wide association study of rubella virus vaccine strain BRD-Ⅱ, so as to fully grasp the sequence characteristics of this genome. MethodsSecond-generation sequencing method was used to conduct the whole-genome sequencing on the vaccine strain BRD-Ⅱ, and the affinity tree of this genome with some vaccine strains and wild-type rubella virus strains was analyzed using the maximum likelihood method. The average genetic distance of nucleic acid sequence of each vaccine strain protein was determined. And homology comparison of structural proteins of each rubella vaccine strain, plus the comparison between this genome with the AY258323.1 genome sequence, were conducted to analyze the homology of E1 protein between the wild-type rubella virus reference strain and vaccine strain BRD-Ⅱ. ResultsThe sequencing results showed that the BRD-Ⅱ strain was a single-molecule single-stranded positive-strand ribonucleic acid (RNA), composed of 9 778 nucleotides, with a GC content of 69.35 %. The C protein was composed of 300 amino acids, the E2 glycoprotein was composed of 282 amino acids, and the E1 glycoprotein was composed of 481 amino acids. The results of preliminary analysis showed that the average genetic distances of nucleic acid sequences were 0.066 700 for the P150 protein, 0.061 933 for the P90 protein, 0.057 850 for the C protein, 0.068 167 for the E2 protein, and 0.068 833 for the E1 protein, respectively. The amino acid sequences in the E2 protein and E1 protein regions of the two BRD-Ⅱ strains did not change, confirming the conserved regions of the E1 protein by comparison. ConclusionThe sequence characteristics of the genome are clarified, which have laid a broad foundation for the subsequent detection of the genetic stability of the main antigen genes.

Objective To investigate the epidemiological characteristics and control measures of dengue fever in Zhongshan City in 2024, so as to provide insights into optimization of dengue fever control strategies in the city. Methods Data pertaining to dengue fever cases in Zhongshan City in 2024 were collected from the Infectious Disease Reporting System of China Disease Prevention and Control Information System, and the epidemiological characteristics of the cases were analyzed using a descriptive statistical method. The density of Aedes albopictus mosquito was monitored across all 23 townships (subdistricts) using Breteau index (BI) and mosquito ovitrap index (MOI) at midmonth each month from March to December 2024. In addition, the climatic characteristics, case reporting patterns, and corresponding control measures were analyzed during different phases of dengue fever epidemics in Zhongshan in 2024. Furthermore, real-time quantitative reverse transcription PCR (RT-qPCR) assay was employed to serotype the dengue virus among local dengue fever cases with unknown sources of infections. The dengue virus envelope (E) gene was sequenced using Sanger sequencing among dengue fever cases without apparent epidemiological links. A phylogenetic tree was constructed using the neighbor-joining method to infer major transmission chains during the dengue fever epi demics. Results A total of 952 dengue fever cases were reported in Zhongshan City in 2024, including 879 local cases, 57 domestically imported cases from other regions, and 16 overseas imported cases, representing the largest outbreak in nearly two decades. The first local dengue fever case was reported on July 5, and the last one was detected on December 19, with all townships and subdistricts affected. Mosquito monitoring data indicated that both MOI and BI rose rapidly from March to May, and then remained at high levels with fluctuations, and began to decline in October. The dengue fever epidemic was categorized into five distinct phases in Zhongshan, including non-epidemic, pre-epidemic, early-epidemic, peak, and receding stages. During the pre-epidemic and early-epidemic phases, key measures included enhancing sensitivity of case detection, implementing isolation and treatment of hospitalized cases, and carrying out standardized vector control measures in affected communities. In the peak phase, the strategy shifted towards targeted mosquito control in key communities and clinical rescue and treatment emphasized on “preventing severe cases and deaths”. Among 481 local cases with unknown sources of infections, RT-qPCR assay revealed that 68.8% (331/481) were infected with dengue virus type I and 31.2% (150/481) with type II among local dengue fever cases in Zhongshan City in 2024. Phylogenetic analysis revealed two major transmission chains: one originating from imported cases within Guangdong Province around Zhongshan City, and another from cases imported from Malaysia. Late detection of local dengue fever cases contributed to widespread community outbreaks. Conclusions The 2024 dengue fever epidemic in Zhongshan City was of considerable scale, which was primarily driven by imported cases from overseas and surrounding regions, leading to local community outbreaks. The epidemic began in early July, increased rapidly during August and September, peaked in October, and subsequently declined, with a trend consistent with the average pattern observed in previous high-incidence years. By implementing differentiated control measures tailored to each phase of the epidemic, the local transmission of dengue fever was successfully contained in Zhongshan City in 2024.

Objective To investigate the effects of periodontitis induced by Prevotella nigrescens(Pn)combined with ligation on cognitive functions in mice.Methods Twenty-four C57BL/6J mice were randomly divided into control group,ligation group,and ligation+Pn treatment(P+Pn)group.Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks.After modeling,alveolar bone resorption was assessed using micro-CT and histological analysis.Learning and memory abilities of the mice were evaluated using open field test(OFT),novel object recognition test(NORT),and Morris water maze test(MWM).Seven weeks after the start of modeling,the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining.Results After 6 weeks of molar ligation,micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice,and histological analysis showed apical migration of the junctional epithelium,epithelial ridge hyperplasia,and lymphocyte infiltration,and these changes were obviously worsened in P+Pn group.Alveolar bone height decreased significantly in both ligation groups compared to the control group.Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT,showed reduced novel object preference in NORT,and exhibited longer escape latencies in MWM,and the mice in P+Pn group had significantly poorer performances in the tests.Histologically,obvious neuronal cytoplasmic degeneration,necrosis,nuclear pyknosis,vacuolation,and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups.Conclusion Pn infection aggravates alveolar bone destruction,accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.

Flow diverter (FD) can significantly improve the occlusion rate and reduce the recurrence rate of intracranial aneurysms, and has become an irreplaceable endovascular treatment option. Delayed aneurysm rupture (DAR) is one of the most serious complications after FD implantation, with a very high mortality rate. It is a major challenge to the safety of FD implantation. The mechanism of DAR is currently not fully understood and may be associated with the changes in hemodynamics after FD implantation, inflammation and mechanical stress within aneurysms, and changes in postoperative coagulation function. This article reviews the research progress on the occurrence mechanism of DAR and outlines future research directions, with the aim of reducing DAR occurrence and optimizing clinical decision-making.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

OBJECTIVES: To investigate the effects of periodontitis induced by Prevotella nigrescens (Pn) combined with ligation on cognitive functions in mice. METHODS: Twenty-four C57BL/6J mice were randomly divided into control group, ligation group, and ligation + Pn treatment (P+Pn) group. Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks. After modeling, alveolar bone resorption was assessed using micro-CT and histological analysis. Learning and memory abilities of the mice were evaluated using open field test (OFT), novel object recognition test (NORT), and Morris water maze test (MWM). Seven weeks after the start of modeling, the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining. RESULTS: After 6 weeks of molar ligation, micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice, and histological analysis showed apical migration of the junctional epithelium, epithelial ridge hyperplasia, and lymphocyte infiltration, and these changes were obviously worsened in P+Pn group. Alveolar bone height decreased significantly in both ligation groups compared to the control group. Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT, showed reduced novel object preference in NORT, and exhibited longer escape latencies in MWM, and the mice in P+Pn group had significantly poorer performances in the tests. Histologically, obvious neuronal cytoplasmic degeneration, necrosis, nuclear pyknosis, vacuolation, and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups. CONCLUSIONS Pn infection aggravates alveolar bone destruction, accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.
Animals ; Periodontitis/microbiology* ; Mice ; Mice, Inbred C57BL ; Cognition ; Alveolar Bone Loss ; Hippocampus/pathology* ; Male ; Inflammation ; Maze Learning

Objective:To explore and analyze the feasibility and efficacy of the 22G needle-guided suture for orbital septum fat flap fixation on the periosteum.Methods:The retrospective study was conducted. From January 2022 to November 2023, patients with tear trough deformity and eyelid bags underwent surgery of releasing the orbicularis retaining ligament (ORL) complex, orbital septum fat pad combined with 22G needle-guided suture in Department of Burn and Plastic Surgery, the First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology. Postoperative follow-up was conducted to observe the occurrence of complications. The lacrimal depression deformity was classified according to the Hirmand standard and the degree of lower eyelid bags was graded to evaluate the surgical outcome. Patients were evaluated their satisfaction using the visual analogue scale (very dissatisfied, dissatisfied, average, satisfied, very satisfied).Results:A total of 32 patients (30 females and 2 males) were included in this study. The age range was 31-62 years old with an average of 50.2 years. All patients were followed up for 6 months postoperatively. None of the patients had any severe complications, such as inferior eyelid ectropion, inferior eyelid retraction, scar hyperplasia, and diplopia. Four patients showed mild eyelid-eyeball separation, two patients had conjunctival edema, and all recovered in 1 month. The orbital fat protrusion, tear trough depression deformity, and lower eyelid skin laxity were significantly improved compared to before the operation. Postoperative satisfaction was 22 cases, very satisfied 10 cases, and patient satisfaction rate was 100% (32/32) after surgery.Conclusion:The method of 22G needle-guided suture to fix orbital septum fat pad represents a technically feasible, easy, and suitable for promotion.

Objective:To investigate the relationship between dietary behavior and sarcopenia in older adults aged ≥65 years in longevity areas of China based on latent class analysis.Methods:A total of 4 358 older adults aged ≥65 years were selected from the 2021 Healthy Aging and Biomarkers Cohort Study. The information about their demographic characteristics, lifestyles, and chronic disease histories were collected. A simplified food frequency questionnaire was used to collect information about their dietary intake in the last month. The food intake frequency and food category score were calculated, and the higher the food category score, the richer the dietary intake. Latent class analysis was used to identify the latent classes of the dietary behavior. Sarcopenia was diagnosed using the SARC-CalF. Multivariate logistic regression model was used to analyze the association of food category scores and different latent classes of the dietary behavior with the risk for sarcopenia.Results:In 4 358 older adults, 1 841 (42.24%) had sarcopenia. The frequencies of intakes of cereals and potatoes, vegetable and fruit, meat and bean products were lower in the sarcopenia group than in the non-sarcopenia group. The risk for sarcopenia decreased with the increase of food category score in older adults ( OR=0.850, 95% CI: 0.796-0.907). Latent class analysis identified 4 latent classes of the dietary behavior. Compared with those with class 1 (frequency of intake of all 5 food species was higher probability in T3 group), those with class 2 (frequency of intake of vegetables and fruits and energy-only foods were less likely to be in the T3 group) and class 3 (frequency of intake of all 5 food species was lower probability in T3 group) had significantly increased risk for sarcopenia ( OR=1.377, 95% CI: 1.131-1.676) and ( OR=1.354, 95% CI: 1.091-1.680), 37.7% and 35.4% increased risk for sarcopenia, respectively. Conclusion:Increasing dietary intake category and sufficient intake of various foods for a balanced dietary pattern can reduce the risk of sarcopenia in older adults.