1.Strategies of HIV-1 Vaccines Based on mRNA Platforms
Pei LIU ; Zhong-Yue FANG ; Xin-Xin CHEN ; Shao-Wei LI ; Ying GU
Progress in Biochemistry and Biophysics 2026;53(4):826-839
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.
2.Study on the correlation between HLA antibodies and pregnancy-related factors, and the predictive value of a random-forest model among female blood donors in Nanning
Fang LU ; Huihui MO ; Wujin SU ; Zhoulin ZHONG ; Hengcong LI ; Yuchen HUANG ; Yuxi CHEN ; Lilan LI ; Yan ZHOU
Chinese Journal of Blood Transfusion 2026;39(3):367-372
Objective: To explore the association between the HLA antibody positivity rate in female blood donors and pregnancy history, number of pregnancies, interval from the last pregnancy to blood donation, and age, to identify associated variables using a univariate generalized additive model (GAM), and to further analyze the predictive role of characteristic variables for HLA antibody positivity using a random forest model. Methods: HLA antibody detection was performed on 391 female blood donors using the Luminex immunomagnetic bead method. The correlation between pregnancy-related factors and HLA antibodies was analyzed using the Chi-square test. Based on R software, a univariate GAM was first constructed to analyze the association types between characteristic variables and the HLA antibody positivity rate, followed by the construction of a random forest model to evaluate the predictive value of the variables. Results: Among the 391 female blood donors without a transfusion history, the overall HLA antibody positivity rate was 26.34%. The positivity rate in donors with a pregnancy history was significantly higher than that in those without (30.09% vs 9.72%, P<0.05), and HLA antibody positivity rate increased linearly with the number of pregnancies (P<0.05). In the univariate GAM, age and number of deliveries exhibited a non-linear association with the HLA antibody positivity rate (the positivity rate increased sharply between 25-35 years of age and stabilized after 3 deliveries). Besides, the interval from the last pregnancy to blood donation showed a linear association with the HLA antibody positivity rate, and the positivity rate decreased as the interval prolonged (P<0.05). In the random forest model, age (mean decrease gini=29.26) and interval from the last pregnancy to blood donation (mean decrease gini=22.02) were core predictive variables: age was more conducive to identifying positive samples, while the interval from the last pregnancy to blood donation was more helpful for excluding negative samples. The number of deliveries (mean decrease accuracy=16.98) made a significant contribution to predicting positive samples, whereas the number of abortions had no impact. The model had an AUC of 0.583 (95% CI: 0.593 8-0.770 2), indicating a certain predictive value. Conclusion: The associated variables identified by the univariate GAM model, including age, interval from the last pregnancy to blood donation, and number of deliveries, provide a basis for key variables in the random forest model. All three variables have predictive value for HLA antibody positivity, which can provide evidence-based support for personalized transfusion management and stratified screening of female blood donors in this region.
3.Hypoglycemic Effect and Mechanism of ICK Pattern Peptides
Lin-Fang CHEN ; Jia-Fan ZHANG ; Ye-Ning GUO ; Hui-Zhong HUANG ; Kang-Hong HU ; Chen-Guang YAO
Progress in Biochemistry and Biophysics 2025;52(1):50-60
Diabetes is a very complex endocrine disease whose common feature is the increase in blood glucose concentration. Persistent hyperglycemia can lead to blindness, kidney and heart disease, neurodegeneration, and many other serious complications that have a significant impact on human health and quality of life. The number of people with diabetes is increasing yearly. The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million), and it will rise to 12.2% (783.2 million) in 2045. The main modes of intervention for diabetes include medication, dietary management, and exercise conditioning. Medication is the mainstay of treatment. Marketed diabetes drugs such as metformin and insulin, as well as GLP-1 receptor agonists, are effective in controlling blood sugar levels to some extent, but the preventive and therapeutic effects are still unsatisfactory. Peptide drugs have many advantages such as low toxicity, high target specificity, and good biocompatibility, which opens up new avenues for the treatment of diabetes and other diseases. Currently, insulin and its analogs are by far the main life-saving drugs in clinical diabetes treatment, enabling effective control of blood glucose levels, but the risk of hypoglycemia is relatively high and treatment is limited by the route of delivery. New and oral anti-diabetic drugs have always been a market demand and research hotspot. Inhibitor cystine knot (ICK) peptides are a class of multifunctional cyclic peptides. In structure, they contain three conserved disulfide bonds (C3-C20, C7-C22, and C15-C32) form a compact “knot” structure, which can resist degradation of digestive protease. Recent studies have shown that ICK peptides derived from legume, such as PA1b, Aglycin, Vglycin, Iglycin, Dglycin, and aM1, exhibit excellent regulatory activities on glucose and lipid metabolism at the cellular and animal levels. Mechanistically, ICK peptides promote glucose utilization by muscle and liver through activation of IR/AKT signaling pathway, which also improves insulin resistance. They can repair the damaged pancrease through activation of PI3K/AKT/Erk signaling pathway, thus lowering blood glucose. The biostability and hypoglycemic efficacy of the ICK peptides meet the requirements for commercialization of oral drugs, and in theory, they can be developed into natural oral anti-diabetes peptide drugs. In this review, the structural properties, activity and mechanism of ICK pattern peptides in regulating glucose and lipid metabolism were summaried, which provided a reference for the development of new oral peptides for diabetes.
4.Prognostic Factors of Liposarcoma in Head and Neck
Shuo DING ; Zhigang HUANG ; Jugao FANG ; Yang ZHANG ; Lizhen HOU ; Wei GUO ; Gaofei YIN ; Qi ZHONG
Cancer Research on Prevention and Treatment 2025;52(1):31-35
Objective To explore the pathogenesis and prognostic factors of liposarcoma in the head and neck region, and simultaneously analyze the efficacy of different treatment regimens. Methods A retrospective analysis was performed on all patients with primary untreated head and neck liposarcoma who were diagnosed and underwent surgical treatment at our hospital from January 2008 to January 2024. All patients were monitored during follow-up, and their prognoses were analyzed using SPSS software. Results A total of 30 patients were included in the study. Liposarcoma accounted for up to 60% of the cases in the orbit, while the remaining liposarcomas were primarily located in various interspaces of the neck. Dedifferentiated liposarcoma was the most common type, comprising 33%, while myxoid pleomorphic liposarcoma was the rarest at 4%. The tumor pathological type (P<0.001) and Ki67 (P=0.014) significantly affected the tumor control rate. However, an analysis of disease-specific survival rates revealed no significant differences across various factors (all P>0.05). Conclusion The prognosis of head and neck liposarcoma is better compared to that of liposarcomas in other parts of the body. However, myxoid pleomorphic liposarcoma, pleomorphic fat sarcoma, and high Ki67 levels are indicators of poor prognosis. Additionally, postoperative adjuvant radiotherapy does not significantly enhance disease-specific survival rates.
5.Genetic evolution characteristics and their influence on disease transmission in sandflies in various environments in China
Lei CUI ; Ya-qi HE ; Zheng-bin ZHOU ; Yuan FANG ; Zhong-qiu LI ; Yuan-yuan LI ; Li-min YANG ; Yi ZHANG
Chinese Journal of Zoonoses 2025;41(5):501-507
This study analyzed the genetic evolutionary characteristics of sandflies and their effects on the spread of kala-azar in various environments in endemic provinces in China,to provide a scientific basis for kala-azar disease prevention and control.Sand-flies were collected in kala-azar endemic areas such as southern Xinjiang,the large hilly areas of southern Gansu,the northern Sich-uan and Taihang Mountains,and surrounding small hills.The cytochrome c oxidase subunit I and cytochrome b gene fragments of mito-chondrial DNA were amplified to identify sandfly species.The COI and Cytb gene sequences of sandflies from southern Xinjiang and Si-chuan recorded in NCBI were also collected.The intraspecific and interspecific genetic differences of sandflies were calculated in MEGA11.0,and a phylogenetic tree was constructed through the neighbor-joining method,for analysis of the genetic and evolutionary characteristics of sandfly populations and their effects on disease transmission.A total of 155 sandflies were collected from nine sam-pling sites in seven provinces of China;the species included Phlebotomus chinensis,Phlebotomus wui,and Sergentomyia squamirostris.Five sandfly species belonging to two genera were collected:P.chinensis,P.wui,and Phlebotomus alexandri in the genus Phleboto-mus,and S.squamirostris in the genus Sergentomyia.Genetic evolution analysis based on COI and Cytb gene sequences indicated intra-specific genetic distances of 0-0.062 and 0-0.056,respectively,and interspecific genetic distances of 0.126-0.176 and 0.110-0.171,respectively.The phylogenetic tree indicated that P.wui,P.alexandri,Phlebotomus longiductus,and S.squamirostris clus-tered into one branch.The sequences of P.chinensis in the large and small hilly areas clustered into two geographical clades.In the small hilly areas,the sequences of P.chinensis aggregates showed small genetic differences,the pathogen infection was consistent,and the cases showed an epidemic spread trend.Large genetic differences at the molecular level were observed among sandflies in dif-ferent ecological regions,thus indicating key effects on leishmaniasis transmission.On the basis of these findings,prevention and con-trol strategies should be adapted to local conditions,and precise and effective prevention and control measures should be formulated according to the genetic evolution characteristics of sandflies in different regions,to better control the transmission of Kala-azar.
6.Research on cultural adaptation in the Chinese version of the inflammatory bowel disease self-efficacy scale for adolescents and young adults
Yuan MENG ; Xiaolu NIE ; Xin WANG ; Fang HU ; Siyu CAI ; Zhaoxia WANG ; Xuemei ZHONG ; Jie WU
Chinese Pediatric Emergency Medicine 2025;32(5):341-346
Objective:By using cognitive interviews,the interviewees' cognition and understanding of the inflammatory bowel disease(IBD) self-efficacy scale for adolescents and young adults (IBDSES-A) were evaluated,and the semantic content of IBDSES-A,which was initially translated into Chinese,was tested and revised.Methods:Using purposive sampling,15 IBD patients aged 12-18 were selected from Beijing Children's Hospital,Capital Medical University,between January and February 2025,stratified by age group and disease type.Two rounds of cognitive interviews were conducted.Feedback and suggestions from interviewees were analyzed using a question appraisal system for coding and integration.Based on expert panel discussions,ambiguous items were revised to finalize the Chinese version of the IBDSES-A.Results:In the first round,10 interviewees were interviewed,followed by 5 interviewees in the second round.There were no statistically significant differences ( P>0.05) between the interviewees of two rounds in terms of age,gender,and education level.During the first round of interview,interviewees expressed comprehension difficulties with 76.9% (10/13) of the items.Coding analysis revealed that the primary issue was "clarification",as unclear wording made it difficult for interviewees to fully grasp the intended meaning of certain items.Based on these findings,the expert panel revised 10 of the 13 items in the IBDSES-A.The second round of cognitive interview showed that the interviewees generally understood the revised items,achieving linguistic and semantic consistency with the original scale. Conclusion:The application of cognitive interviews in the translation process of the IBDSES-A helps reduce comprehension biases caused by inappropriate wording,ensuring that the localized version of the scale is more accessible and understandable to the target population.
7.The significance of preoperative neck enhanced multidetector computed tomography in predicting the recurrent veins and classifying their courses of the submental flap reflux vein for repair in pharyngeal cancer
Qian SHI ; Jugao FANG ; Qi ZHONG ; Lizhen HOU ; Hongzhi MA ; Ling FENG ; Shizhi HE ; Meng LIAN ; Yanming ZHAO ; Ru WANG ; Yunxia LI ; Xixi SHEN ; Yifan YANG ; Lingwa WANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(10):1208-1214
Objective:To evaluate preoperative high-resolution thin-layer cervical enhanced CT used to predict the venous route of the submental flap reflux vein and its relationship with adjacent structures in order to guide the anatomical understanding and protection of submental flap in pharyngeal cancer surgery.Methods:Sixty consecutive patients with pharyngeal cancer who underwent submental flap repair surgery in our department from March 2022 to December 2024, as well as 60 patients who were accepted neck dissection suffering other cancers, were selected. Before surgery, high-resolution cervical enhanced CT scans were performed, and the position of the transverse section of the facial vein in the venous phase horizontal image gradually variation tendency was focused layer by layer. The direction and adjacent relationship of the submental flap reflux veins were determined and recorded. Combined with 60 patients with other head and neck tumors who underwent neck dissection in our department during the same period (a total of 120 cases, 240 sides), the classification and management of the draining veins of Fang′s mental flap were conducted. Type Ⅰ mainly drains into the internal jugular vein; Type Ⅱ mainly drains into the external jugular vein and Type Ⅲ mainly drains into the anterior jugular vein (often accompanied by an external jugular draining branch). The status and proportion of venous drainage were analyzed.Results:Vascular predictive coincidence rate was 98.3% (59/60) among the 60 patients with pharyngeal cancer. Only one patient was predicted to have a simple return to the external jugular vein. However, during the operation, in addition to the main return to the external jugular vein, a small portion also returned to the internal jugular vein. Submental flap reflux vessels were classified into three types based on intraoperative submental flap venous return in 60 cases of laryngopharyngeal cancer, in conjunction with the analysis of venous return patterns from 240 cervical CT scans. Type Ⅰ mainly refluxed to the internal jugular vein, accounting for 42.1%. Type Ⅱ mainly refluxed to the external jugular vein (47.9%). Type Ⅲ mainly refluxed to the anterior jugular vein (10.0%). The total detection rate of CT reading of 240 venous reflux was 98.7% (237/240). Vascular predictive coincidence rate was 97.9%(235/240).Conclusion:The detailed analysis of submental venous return vessels can accurately predict the direction of reflux veins and its surrounding areas by preoperative high-resolution enhanced CT scan. This provides reliable guidance for the anatomy and protection of the submental flap reflux veins during surgery.
8.Efficacy comparison of subsequent treatment modalities for locally advanced hypopharyngeal cancer with partial response to neoadjuvant chemotherapy
Ru WANG ; Zheng LI ; Jugao FANG ; Junfang XIAN ; Qi ZHONG ; Yang ZHANG ; Lizhen HOU ; Hongzhi MA ; Ling FENG ; Shizhi HE ; Qian SHI ; Yifan YANG ; Haiyang LI ; Lingwa WANG ; Xinyu LI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(10):1223-1231
Objective:To compare the survival outcomes of different subsequent treatment regimens in patients with locally advanced hypopharyngeal squamous cell carcinoma (HPSCC) who achieved partial response (PR) after neoadjuvant chemotherapy based on the gross tumor volume regression rate (GTVRR).Methods:This retrospective study included patients with locally advanced HPSCC treated at the Department of Head and Neck Surgery, Beijing Tongren Hospital, from January 2011 to December 2023. The cohort included 135 males and 3 females, aged from 35 to 77 years. All patients received 2-3 cycles of TPF regimen (paclitaxel+cisplatin+5-fluorouracil) neoadjuvant chemotherapy. Subsequent treatments included concurrent chemoradiotherapy or surgery combined with postoperative adjuvant radiotherapy. The impacts of different subsequent treatment modalities on the survivals and prognoses of patients were compared based on GTVRR thresholds of 50% and 70%. The χ 2 test was used to analyze influencing factors; survival analysis and intergroup comparisons were performed using the Kaplan-Meier method and Log-rank test; prognostic factors were assessed using univariate and multivariate Cox regression analyses. Results:The 5-year OS and PFS rates were 56.5% and 47.9%, respectively, while, the 10-year OS and PFS rates were 25.8% and 21.2%, respectively. The median OS was 75 months, and the median PFS was 48 months. The laryngeal function preservation rate for the entire cohort was 83.3%. The patients who underwent surgery combined with postoperative radiotherapy had significantly better OS and PFS outcomes than those treated with concurrent chemoradiotherapy ( P<0.05). Stratification based on GTVRR revealed that the surgery plus postoperative radiotherapy regimen was particularly effective for PR patients with a GTVRR of 30%-70%, showing significantly better OS and PFS compared to the concurrent chemoradiotherapy group ( P<0.05). Conclusion:The optimal subsequent treatment for PR-HPSCC may be surgery-based comprehensive treatment, particularly for patients with a GTVRR of 30%-70%. This study offers valuable insights for the stratified treatment of HPSCC, which could contribute to improving overall patient prognosis.
9.Analysis of influencing factors of prolonged hospitalization in elderly patients based on generalized estimation equation
Fang ZENG ; Li ZHAO ; Ying XIONG ; Bin ZHONG
Chinese Journal of Geriatrics 2025;44(5):664-670
Objective:To analyze the distribution characteristics and influencing factors of prolonged length in the elderly patients at a tertiary hospital.Methods:Medical records of patients receiving inpatient care at Xiangya Hospital, Central South University in Hunan province during January 1, 2021 and December 31, 2023 were collected.The generalized estimating equation(GEE)model was used to analyze the factors influencing prolonged hospitalization in elderly patients.Results:A total of 144 921 elderly inpatients were included, aged 60 to 104 years, with 84 950 males and 59 971 females.The average length of hospitalization was 7.81 days, with 2 614 patients hospitalized for more than 30 days (1 663 males and 951 females), and the average length of stay for these patients was 44.93 days.Most of the patients with prolonged length were hospitalized for 30 to 40 days, and in the group of aged 60-74 years.Disease categories mainly were related to health conditions, healthcare facility contact, tumors, and circulatory system diseases.The GEE model analysis showed that nosocomial infection [ OR(95% CI): 5.836(4.716-7.221)], age≥90 [ OR(95% CI): 2.415(1.680-3.472)], surgery [ OR(95% CI): 3.543(2.925-4.291)], number of complications>4[ OR(95% CI): 2.378(2.091-2.704)], unplanned hospital readmissions within 31 days [ OR(95% CI): 1.748(1.525-2.004)]were risk factors of prolonged hospitalization; female [ OR(95% CI): 0.901(0.824-0.986)] and no transferred hospitalization [ OR(95% CI): 0.154(0.140-0.169)] were protective factors. Conclusions:Prolonged hospitalization is related to the clinical and social factors.Administration department of the hospital should strengthen the monitoring of these influencing factors, reduce or prevent the occurrence of prolonged length of stay by adopting targeted measures, and further realize rational allocation of medical resources.
10.Sinicization and reliability and validity test of the Obsessive and Compulsive Behaviors Scale of Mothers in Postpartum Period Regarding Baby Care
Hangcheng LIU ; Xixi LI ; Xiaoying ZHONG ; Haoyue GAN ; Hongjin WU ; Linqian HE ; Fang YANG
Chinese Journal of Practical Nursing 2025;41(2):103-111
Objective:To sinicize the Obsessive and Compulsive Behaviors Scale of Mothers in Postpartum Period Regarding Baby Care (OCBS-MPPRBC) to test its reliability and validity, and to provide an evaluation tool for evaluating the degree of compulsive behaviors of postpartum mothers regarding baby care.Methods:Following the principles of Brislin translation, back translation and cross-cultural adaptation, the Chinese version of OCBS-MPPRBC was formed. A convenient sampling method was used to investigate 360 women in Mianyang Central Hospital from November 2023 to February 2024, and to test the reliability and validity of the Chinese version OCBS-MPPRBC. The critical ratio method and the total correlation analysis method were used for item analysis, the reliability test was based on Cronbach α coefficient and half-reliability method, and the content validity index, exploratory factor analysis, confirmatory factor analysis and aggregate validity were used for validity test. Results:A total of 352 women aged 21-41 (31.55 ± 3.17) years who met the exclusion criteria were included. The Chinese version of OCBS-MPPRBC contained 9 items, and 2 common factors were extracted by exploratory factor analysis, and the cumulative total variance contribution rate was 65.523%. The content validity index of the scale level was 0.89, the content validity index of each item level was 0.86-1.00, and the Cronbach α coefficient of the total scale was 0.844, and the half-folded reliability was 0.759. The results of confirmatory factor analysis showed that the fitting index of the Chinese version of the OCBS-MPPRBC model was better. Conclusions:The Chinese version of the OCBS-MPPRBC scale has good reliability and validity, and has good operability, which can be used to evaluate the degree of compulsive behavior of postpartum mothers about baby care in China.

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