Since its emergence in the 1980s, the human immunodeficiency virus (HIV) has caused a global pandemic, posing a severe threat to human life and health as well as social development. Although pre-exposure prophylaxis (PrEP) effectively curbs HIV transmission and antiretroviral therapy (ART) significantly extends the lifespan of patients, vaccines remain a pivotal tool for blocking transmission and ending the pandemic. The high genetic variability of HIV-1, the glycan shield of its envelope glycoproteins, and the long-term persistence of latent reservoirs have repeatedly led to bottlenecks in traditional vaccine strategies. In recent years, mRNA technology has offered a novel approach to addressing these challenges, leveraging advantages such as sequence programmability, short production cycles, native conformational expression of antigens, and self-adjuvant effects. In recent years, mRNA vaccine technology has emerged as a transformative solution to longstanding vaccinology challenges, characterized by its sequence programmability, rapid production cycles, native conformational antigen expression, and intrinsic self-adjuvanting properties. Unlike traditional platforms reliant on pathogen culture or recombinant proteins, mRNA vaccines can be expeditiously designed and updated based solely on viral genomic sequences. Lipid nanoparticle (LNP)-encapsulated mRNA facilitates endogenous antigen expression and presentation, simultaneously eliciting potent humoral and cellular immune responses. Within this landscape, self-amplifying mRNA (saRNA) further extends in vivo antigen expression to enhance the persistence of immune responses. Moreover, the LNP delivery system not only protects mRNA from degradation and mediates endosomal escape but also synergizes with mRNA to optimize immune activation via self-adjuvant effects. Importantly, mRNA platforms circumvent the pre-existing immunity associated with viral vectors and the genomic integration risks of DNA vaccines, positioning them as a cornerstone for global pandemic preparedness. This review systematically delineates recent advances in mRNA technology for HIV-1 vaccine development, focusing on four pivotal research frontiers. First, mRNA innovations building upon the RV144 trial optimize antigens through codon modification and multivalent designs to induce more durable and broad-spectrum immunity. Second, particulate mRNA vaccine strategies, utilizing virus-like particles (VLPs) and ferritin nanoparticles, achieve in situ antigen self-assembly, significantly enhancing B cell activation and reducing infection risks in non-human primate models. Third, germline-targeting mRNA vaccines address the low-affinity barrier of broadly neutralizing antibody (bNAp) precursors, efficiently activating rare precursor B cells and promoting affinity maturation. Fourth, therapeutic mRNA vaccines offer unique advantages for an HIV functional cure; combining immunogens with mRNA-encoded adjuvants potentiates cellular immunity, while LNP-mediated “shock-and-kill” strategies specifically activate latent reservoirs to guide immune clearance. Comparative analyses with traditional platforms reveal that mRNA technology redefines antigen production and presentation, simulating chronic infection through sustained expression and enabling dual-pathway presentation via endogenous synthesis. Furthermore, we explore the mechanistic innovations of mRNA vaccines in inducing bNAps: sustained in vivo production prolongs the activation window for precursor B cells and maintains germinal center (GC) reactions; endogenously expressed antigens adopt native conformations to expose conserved epitopes; and self-adjuvanting effects modulate the functions of antigen-presenting cells (APCs) and follicular helper T cells (Tfh), driving somatic hypermutation and affinity maturation. We also address critical clinical translation challenges, including immune durability, adaptability to special populations, and large-scale LNP manufacturing, while proposing targeted optimization strategies. In conclusion, this review establishes a theoretical framework for utilizing mRNA technology to overcome HIV-1 immune escape, transitioning from a descriptive paradigm to a problem-solving-based synthesis of evidence. By integrating preclinical and early clinical data, we bridge the gap between basic design and translational verification. mRNA technology is poised to become a central pillar inHIV-1 prevention and therapy, providing a robust toolset to achieve the global goal of ending the AIDS pandemic and offering a blueprint for vaccine development against other recalcitrant infectious diseases.

To explore the understanding of the target population regarding the Get Active Questionnaire for Pregnancy(GAQ-P)and the Companion Health Care Provider Consultation Form for Prenatal Physical Activity(cHCP-CF-PPA)in the Chinese context,and to verify the consistency of the Chinese version of the prenatal physical activity dual screening questionnaire with the original version in terms of language expression,27 pregnant women and 12 healthcare providers were selected from Obstetrics and Gynecology Hospital,Fudan University during Aug and Oct 2023,and were interviewed using purposive sampling.Two rounds of cognitive interviews were conducted.The first round revealed that some respondents experienced ambiguities in understanding the meanings of 5 items in the questionnaire.Following modifications,the second round indicated that the revised items were consistent in meaning with the original questionnaire.Cognitive interviews can facilitate the adaptation of the prenatal physical activity dual screening questionnaire to the Chinese cultural context,improve the understanding of the questionnaire items among the target population,and promote the localization of the screening tool.

OBJECTIVE To explore the association of Helicobacter pylori infection with the expression levels of Ki67,caudal type homeobox transcription factor 2(CDX-2)and p53 protein in the gastric cancer patients so as to provide bases for improvement of prognosis of the gastric cancer patients.METHODS Totally 113 patients who were diagnosed with gastric cancer by gastroscopic examination and were treated in Shijiazhuang People's Hospital from Jan.2020 to Jan.2024 were assigned as the gastric cancer group,84 of whom were complicated with H.py-lori infection(the Hp-positive group),and 29 were negative for Hp(the Hp-negative group).Meanwhile,125 patients who had chronic atrophic gastritis were assigned as the non-gastric cancer group.The gastric mucosa tis-sue specimens were collected through gastroscopy,and the expression levels of Ki67,CDX-2 and p53 protein were detected.RESULTS The positive rate of H.pylori infection of the gastric cancer group was 74.34％,higher than 54.40％of the non-gastric cancer group(P＜0.05).The positive rate of H.pylori was higher in the gastric canc-er patients with lymphatic metastasis,infiltration depth of T3 to T4 and TNM stage of Ⅲ to Ⅳ stage than in the gastric cancer patients without lymphatic metastasis,infiltration depth of T1 to T2 and TNM stage of Ⅰ to Ⅱ stage(P＜0.05).The positive expression rates of gastric mucosa tissue Ki67,CDX-2 and p53 protein of the gastric cancer group were respectively 69.91％,52.21％and 79.65％,higher than 47.20％,0 and 24.00％of the non-gastric cancer group,there were significant differences(P＜0.05).The positive expression rates of gastric mucosa tissue Ki67,CDX-2 and p53 protein of the Hp-positive group were higher than those of the Hp-negative group(P＜0.05).CONCLUSION The gastric cancer is associated with the H.pylori infection and the expressions of Ki67,CDX-2 and p53.The H.pylori infection may lead to the abnormal expressions of Ki67,CDX-2 and p53 in gastric mucosa tissues of the gastric cancer patients,which is also associated with the clinicopathologic features.

BACKGROUND:Compensatory changes in sagittal parameters of the cervicothoracic spine after orthopedic surgery in patients with lumbar degenerative scoliosis and their intrinsic relationship,as well as the impact of these changes on quality of life,are still lacking.OBJECTIVE:To evaluate the compensatory alignment of cervical and thoracic vertebrae after correction of lumbar degenerative scoliosis.METHODS:103 patients who underwent surgical correction of lumbar degenerative scoliosis were included in this study.Patients'demographic characteristics and spinal sagittal parameters were assessed,and prediction equations between changes in cervical sagittal parameters and lumbar deformity correction were attempted.Simultaneously,the SRS-22 scale was used to assess the quality of life of patients and to explore the relationship between the compensatory changes of the cervical and thoracic spine after correction and the patients'health-related quality of life.RESULTS AND CONCLUSION:(1)At 3 months and 2 years after surgery,all indicators of the cervical spine and thoracic spine were significantly improved compared with those before surgery(P＜0.05),but there was no significant change at 3 months after surgery compared with 2 years after surgery(P＞0.05).At 3 months and 2 years after surgery,the lumbar spine parameters including lumbar lordosis,C7-S1 sagittal vertical axis,and pelvic incident-lumbar lordosis had significant changes compared with those before surgery(P＜0.05),but the change was not significant at 3 months after surgery compared with 2 years after surgery(P＞0.05).(2)Correlation analysis showed that the lumbar lordosis was highly correlated with the C3-C7 cervical lordosis,C1-C7 cervical lordosis,C2-7 sagittal vertical axis,thoracic inlet angle,and C7-S1 sagittal vertical axis(|r|≥ 0.5,P＜0.000 1).The lumbar lordosis was correlated with the thoracic kyphosis(r=-0.280).(3)Two prediction formulas were established for compensatory changes in cervical spine:cervical lordosis=0.524x,lumbar lordosis=-6.612,C2-7 sagittal vertical axis=-0.263x,and lumbar lordosis=-5.436(P＜0.05,R2＞0.6).(4)When postoperative C2-7 sagittal vertical axis was between 14.4 and 26.8 mm;cervical lordosis was between 9° and 41°,lumbar lordosis was between 42.7° and 68.7°,and sagittal vertical axis was between-40 and 40 mm,patients had better quality of life recovery.(5)It is indicated that significant compensatory changes in the sagittal plane of the cervical spine can be observed after correction of lumbar degenerative scoliosis.We found that each 1° increase in lumbar lordosis was associated with a corresponding increase of about 0.5° in cervical lordosis and a corresponding decrease of about 0.3 mm in the vertical axis of the C2-7 sagittal plane.Patient satisfaction was higher if compensatory changes were closer to normal sagittal plane.

Objective To explore the clinical and pathological characteristics and oncological outcomes of clear cell borderline ovarian tumor(CCBOT),and provide guidance for the diagnosis and treatment of this disease in the future.Methods A total of 23 CCBOT patients who underwent surgical treatment in our hospital from May 2011 to Aug 2022 were enrolled,and the clinical information of 19 CCBOT patients in the Ricotta's cohort was integrated.The clinical pathological characteristics and oncological outcomes of these 42 patients were retrospectively analyzed.Results This study enrolled 42 CCBOT patients,including 23 from our cohort and 19 from the Ricotta G's cohort.Compared with the Ricotta's cohort,the proportion of CCBOT patients with endometriosis in our cohort(34.8%)was significantly higher than that in the Ricotta's cohort(5.3%)(P<0.05).In our cohort,22 patients had information on intraoperative frozen section evaluation,and the accuracy of intraoperative frozen section evaluation was 50%(11/22).The other 50%(11/22)of patients were underestimated by intraoperative frozen section evaluation.The merged cohort indicated that the median age of the patients was 60 years old,occuring more common in postmenopausal women(66.7%).Most cases presented with pelvic masses(59.5%)and abdominal pain or distension(19.0%).This disease mostly involved unilateral ovaries(90.5%).Information on preoperative tumor markers was largely missed,making it difficult to draw an accurate evaluation for them.Ten cases(23.8%)underwent fertility sparing surgery,and 32 cases(76.2%)underwent radical surgery.The pathologic report indicated that all patients were stage I patients and 21.4%patients had endometriosis.Among these patients,32 patients underwent total hysterectomy,of which 10(31.3%)had concurrent endometrial lesions.The median follow-up time was 68 months,with a minimum follow-up of one month and a maximum follow-up of 231 months,and no recurrence or death was observed.Conclusion CCBOT patients usually had an good prognosis with a low recurrence rate.Fertility sparing surgery was safe and feasible,but attention should be paid to exclude concurrent endometrial lesions.Given the rarity of CCBOT,future multicenter prospective studies are needed to better elucidate the clinical pathological features and prognosis of patients with CCBOT.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective The study attempted to establish a less invasive model for dissecting and monitoring the sympathetic nerve in rats via a dorsal approach for subarachnoid block-related studies.Methods A traditional abdominal approach model and a new dorsal approach model were established in SD rats,and the modeling time of the two models was observed.The stability of the new model was evaluated by measuring blood pressure(BP),heart rate(HR),percentage change in lumbar sympathetic nerve activity(LSNA change％),norepinephrine(NE),and nitric oxide(NO)content after subarachnoid injection of bupivacaine.Results(1)Building a new model:the time required to create new models for the dorsal approach(DA)group was shorter than that for the traditional abdominal approach(VA)group,as shown by the result(P＜0.0001).(2)Evaluation of the new model:compared with the NS group,the MAP and SBP were lower at T2(5 min after injection of bupivacaine into the subarachnoid space)and T3(10 min)(P＜0.05);the LSNA change％was significantly different(P＜0.05);the concentration of NE was lower at T3(P＜0.05).Conclusions The study presents a novel lumbar sympathetic anatomy model using the dorsal approach for subarachnoid-related investigations,which was effectively employed to examine the impact of subarachnoid block anesthesia on lumbar sympathetic nerve activity.

OBJECTIVE T o assess the in vitro antimicrobial activity of aztreonam-avibactam against metallo-β—lacta-mase(MBL)-producing carbapenem-resistant Enterobacteriaceae(CRE)using different antimicrobial susceptibility testing methods,evaluate the consistency of results based on the latest breakpoints recommended by European Committee on Antimicrobial Susceptibility Testing(EUCAST),and analyze the clinical applicability.METHODS The imipenem-or meropenem-resistant Enterobacteriaceae strains were isolated from the clinical specimens of Bei-jing Chaoyang Hospital from Jan.2019 to Mar.2023,MBL-producing CRE were selected after they were con-firmed by colloidal gold immunoassay and Sanger sequencing as the study subjects.The minimum inhibitory con-centrations(MICs)of single aztreonam and aztreonam-avibactam compounds were determined by using broth mi-crodilution method.In addition,the disk diffusion method and the gradient diffusion method were employed to further detect the in vitro susceptibility to aztreonam-avibactam.RESULTS Among the 87 strains of MBL-producing CRE that were included in the study,Escherichia coli was the most common species,accounting for 44.83％.NDM-5 was the predominant carbapenemase type,detected in 48.28％of the isolates.According to the latest EUCAST break-points,6 isolates were aztreonam-avibactam-resistant strains based on broth microdilution method,all of which were E.coli,and the resistance rate was 6.90％(6/87).However,the resistance rate that was determined by the disk diffu-sion method was significantly higher(22.99％,20/87).Among these,14 strains was within the area of technical uncer-tainty/resistant,making result interpretation difficult.In addition,the categorical agreement between the gradient diffu-sion method and the broth microdilution method reached up to 98.85％.CONCLUSIONS Aztreonam-avibactam has high antimicrobial activity against MBL-producing CRE.However,based on the latest EUCAST breakpoints,the antimicrobial susceptibility testing by the disk diffusion method results of some strains are hard to interpret.It is necessary to integrate with other methods for further validation.

Objective The study attempted to establish a less invasive model for dissecting and monitoring the sympathetic nerve in rats via a dorsal approach for subarachnoid block-related studies.Methods A traditional abdominal approach model and a new dorsal approach model were established in SD rats,and the modeling time of the two models was observed.The stability of the new model was evaluated by measuring blood pressure(BP),heart rate(HR),percentage change in lumbar sympathetic nerve activity(LSNA change％),norepinephrine(NE),and nitric oxide(NO)content after subarachnoid injection of bupivacaine.Results(1)Building a new model:the time required to create new models for the dorsal approach(DA)group was shorter than that for the traditional abdominal approach(VA)group,as shown by the result(P＜0.0001).(2)Evaluation of the new model:compared with the NS group,the MAP and SBP were lower at T2(5 min after injection of bupivacaine into the subarachnoid space)and T3(10 min)(P＜0.05);the LSNA change％was significantly different(P＜0.05);the concentration of NE was lower at T3(P＜0.05).Conclusions The study presents a novel lumbar sympathetic anatomy model using the dorsal approach for subarachnoid-related investigations,which was effectively employed to examine the impact of subarachnoid block anesthesia on lumbar sympathetic nerve activity.

Objective:To establish and validate a predictive model for non-curative resection of rectal neuroendocrine tumors (R-NETs) ≤20 mm.Methods:Data from patients with R-NETs treated at the First Affiliated Hospital of Soochow University and the Suzhou Ninth People's Hospital from January 2013 to December 2023 were retrospectively analyzed. Clinical data, endoscopic findings, and pathological characteristics were analyzed. Univariate analysis was performed using independent sample t-tests and Chi-square tests. Variables were screened using the forward stepwise binary logistic regression to establish a risk prediction model for non-curative resection of R-NETs ≤20 mm, with subsequent construction of a nomogram. The performance of the model was evaluated using the receiver operating characteristic (ROC) curve. The consistency between predicted and observed probabilities was assessed using calibration curves, and the clinical net benefit of the model was evaluated using decision curve analysis. Results:A total of 213 patients were included, with age of 50.53±11.42 years, and 102 (47.9%) were male. The distance of the lesion from the dentate line was 7.11±2.79 cm, and the tumor long diameter was 8.24±3.75 mm. Compared to curative resection cases, non-curative resection cases were more likely to exhibit tumor surface depression, higher tumor G-stage, higher Ki-67 index and higher chromograninA (CgA) positivity rate ( P<0.05). Through forward variable selection in binary logistic regression, a model was established with Ki-67 index ( P=0.014, OR=1.214, 95% CI: 1.039-1.417), surface depression ( P=0.027, OR=2.348, 95% CI: 1.100-5.013), and CgA positivity ( P<0.001, OR=5.399, 95% CI: 2.764-10.544) as parameters, with a corresponding nomogram. The area under the ROC curve of the model was 0.766 (95% CI: 0.696-0.837), and clinical decision curve analysis confirmed its good clinical net benefit. The calibration curve showed good consistency between predicted and observed probabilities. Conclusion:This study establishes a risk prediction model for non-curative resection of R-NETs ≤20 mm based on surface depression, Ki-67 index, and CgA positivity. The model demonstrates strong predictive performance and offers valuable guidance for clinical endoscopists.