This article adopts Professor CHEN Chaozu′s " sanjiao composed by membrane-striae" theory as its foundation to explore the relationship between irritable bowel syndrome and functional/structural abnormalities of the membrane-striae. Sanjiao encompasses both the tangible membrane and the intangible striae. These striae permeate the entire body，and their pathological changes comprehensively reflect qi，body fluids，and fasciae. Based on the physiological function of the membrane-striae in regulating qi and fluids，the pathogenesis of irritable bowel syndrome is characterized by a disharmony of membrane-striae and an imbalance of the qi-fluid interactions. In the early stage，external pathogens，emotional factors，or dietary stimuli often cause membrane-striae constriction and disordered qi-fluid circulation. In the middle stage，stagnant fluids gradually transform into phlegm retention，leading to membrane-striae obstruction. In the late stage，deficiency of vital qi becomes predominant，manifesting as laxity of membrane-striae with impaired control or weakened conduction. The treatment of irritable bowel syndrome should adopt " unblocking" as the guiding principle. In the early stage，therapy should focus on eliminating pathogenic factors and soothing membrane-striae to promptly restore qi-fluid circulation，thereby attaining unblocking through spasm relief. In the middle stage，treatment should focus on resolving tangible obstructions in membrane-striae，achieving unblocking via dredging. In the late stage，the emphasis should shift to reinforcing healthy qi，particularly by strengthening spleen-kidney yang qi，and achieving unblocking through supplementation. Concurrently，throughout the entire treatment process，the regulation of mental state and easing of emotional tension should be integrated to alleviate patient′s anxiety，achieving the goal of holistic treatment of both body and mind.

ObjectiveTo investigate whether Huanglian Jiedutang （HLJD） and its major active constituents （geniposide， baicalin， and berberine） can inhibit the inflammatory response of BV2 cells under lipopolysaccharide （LPS） stimulation via the high-mobility group protein B1 （HMGB1）/Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway， and to explore differences in therapeutic efficacy among the three monomers， their combined formula， and HLJD under equal content ratios. MethodsBV2 microglial cells were used as the primary experimental model. Cell viability was assessed using the cell counting kit-8 （CCK-8） method to examine the effects of different concentrations of dimethyl sulfoxide （DMSO， 0.8%， 0.4%， 0.2%， 0.1%， and 0.05%） on cell viability. IncuCyte was employed to monitor the growth of cells under different concentrations of HLJD （200， 100， 50， 25， 12.5， 6.25 mg·L^-1）. Nitric oxide （NO） assay was used to screen the optimal HLJD concentration. High-performance liquid chromatography （HPLC） determined the content of geniposide， baicalin， and berberine in HLJD， and experimental groups were subsequently established according to the relative proportions of these constituents. CCK-8 assay evaluated cell viability under different treatments. Enzyme-linked immunosorbent assay （ELISA） measured levels of inflammatory factors （TNF-α， IL-1β， IL-6， IL-10） in the supernatant. Flow cytometry assessed the effects of treatments on M1-type polarization of BV2 cells. Western blot determined the expression levels of HMGB1， TLR4， and NF-κB-related proteins. ResultsCompared with the blank group， DMSO at concentrations ≤0.2% did not affect cell viability within 48 h. BV2 cell growth plateaued at 24 h after treatment with 200 mg·L^-1 HLJD. Under stimulation with 2 mg·L^-1 LPS， this concentration of HLJD effectively reduced NO release， and 6 h pre-treatment had a stronger inhibitory effect on NO than direct administration. HPLC results showed that 1 mg of HLJD freeze-dried powder contained approximately 24 μg of geniposide， 15 μg of baicalin， and 30 μg of berberine. Based on these ratios， experimental groups were blank， LPS （2 mg·L^-1）， HLJD （200 mg·L^-1）， monomer combination， geniposide （4.8 mg·L^-1）， baicalin （3 mg·L^-1）， and berberine （6 mg·L^-1）. The monomer combination group consisted of all three active constituents dissolved together. LPS and HLJD or its active constituents did not affect cell viability compared with the blank group. LPS significantly increased TNF-α， IL-1β， IL-6， and IL-10 in the supernatant （P<0.01）. HLJD and its active constituents significantly reduced pro-inflammatory factors TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01） while upregulating anti-inflammatory IL-10 （P<0.01）， with the monomer combination showing the strongest effect （P<0.05， P<0.01）. Compared with the blank group， LPS significantly increased the proportion of CD80⁺CD86⁺ （M1-type） BV2 cells （P<0.01）. HLJD and its constituents partially inhibited M1 polarization （P<0.05， P<0.01）， with the monomer combination exhibiting the most pronounced effect （P<0.05， P<0.01）. Compared with the blank group， LPS upregulated HMGB1， TLR4， and NF-κB-related proteins （P<0.01）， whereas HLJD and its active constituents significantly reduced their expression （P<0.05， P<0.01）， with the monomer combination having the strongest regulatory effect （P<0.05， P<0.01）. ConclusionHLJD and its major active constituents （geniposide， baicalin， berberine） can inhibit LPS-induced inflammatory responses in BV2 cells. The combination of the three active constituents demonstrates the most potent anti-inflammatory effect， significantly attenuating M1-type polarization of BV2 cells via the HMGB1/TLR4/NF-κB signaling pathway.

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.

ObjectiveTo analyze the expression level and clinical significance of Y‑box binding protein‑1（YB1） in tissues and cells of oral squamous cell carcinoma （OSCC）. MethodsBioinformatics analysis， immunohistochemistry， Western blot and qRT-PCR were used to detect the expression of YB1 in OSCC tissues， and the prognosis and survival analysis were performed. The effects of YB1 on the proliferation， migration and invasion of OSCC cells were evaluated by CCK-8， scratch assay and Transwell assay， and the expression changes of phosphoinositide 3-kinase/protein kinase B （PI3K/AKT） signaling pathway and epithelial-mesenchymal transition （EMT） related markers after YB1 knockdown were detected by Western blot. ResultsBioinformation analysis showed that the expression level of YB1 in OSCC samples was higher than that in normal samples （P0.001）， and its expression was correlated with gender （P=0.022） and tumor differentiation degree （P0.001）. Kaplan-Meier plotter survival analysis showed that the survival rate of YB1 was low （Log-rank P=0.012）. Immunohistochemistry， Western blot and qRT-PCR experiments verified that the expression level of YB1 in OSCC tissues was higher than that of normal tissues. The results of cell experiments showed that knockdown of YB1 inhibited the malignant biological behaviors such as proliferation， migration and invasion of OSCC cells. Western blot results showed that the knockdown of YB1 could reduce the protein expression levels of p-PI3K and p-AKT， and inhibit EMT. ConclusionYB1 is highly expressed in tissues and cells in OSCC， and reveals the important role of the YB1/PI3K/AKT axis in the process of EMT of OSCC， which is expected to become a new tumor marker for early diagnosis and treatment and prognosis evaluation of OSCC.

Background: Malignant pleural effusion (MPE), a common complication of advanced cancers, is associated with poor prognosis and reduced quality of life. Although host–tumor interactions are known to drive MPE development, the associated immune dynamics during disease progression remain unclear. Using a Lewis lung carcinoma-induced MPE model in C57BL/6JNidfc mice, we systematically evaluated general parameters and immune cell changes at two-day intervals throughout disease progression. Results: The day of Lewis lung carcinoma cell injection into the pleural space was designated as day 0. By day 10 post-injection (p.i.), MPE-bearing mice exhibited ~ 10% body weight loss, marking the experimental endpoint. Pleural tumor mass and pleural effusion volume were minimal up to day 4 p.i. but increased sharply from day 6 onward.CD45⁺ immune cell counts rose over time, and days 6, 8, and 10 p.i. marked key stages of MPE progression. On day 6, B cells, T cells, and natural killer cells, but not macrophages and neutrophils, increased significantly compared to earlier timepoints. By day 8, all immune cell subsets except T cells exceeded day 6 levels, and at day 10, natural killer cell numbers declined while others continued to increase. Besides, the numbers of CD8⁺ T cells, Th1 cells, regulatory T cells, and M2 macrophages progressively increased from day 6 to 10. Based on these data, days 6 and 10 were defined as early and advanced MPE stages, respectively, with distinct immune phenotypes. In advanced MPE, CD8⁺ T cells displayed reduced IFN-γ, TNF-α, Granzyme B, Perforin, FasL, and Ki-67, but upregulated PD-1 and CTLA-4 relative to early stage. Similarly, Th1 cells showed decreased IFN-γ, TNF-α, and IL-2 production along with reduced Ki-67 expression. Advanced-stage M2 macrophages exhibited lower MHC-II levels and impaired phagocytosis, but higher PD-L1 and IL-10 production, while neutrophils showed reduced TNF-α release and phagocytic activity. Conclusions Our findings characterize the temporal immune dynamics associated with MPE progression in a mouse model, revealing a transition from an early immunostimulatory state to a late immunosuppressive state. This study enhances our understanding of MPE immunopathogenesis and provides a foundation for developing precise, stagespecific therapeutic strategies.

Objective To investigate the epidemiological characteristics and changing trend of typhus in Shaanxi Province from 2005 to 2023 to provide a scientific basis for its prevention and control. Methods Excel 2007, SPSS 25.0, Joinpoint 4.9.1.0, and Geoda 1.6 were used for data collection and statistical analysis. Super Map was used for data visualization to describe the changing characteristics of the disease. Results A total of 394 typhus cases were reported in Shaanxi Province from 2005 to 2023. The average annual incidence of typhus was 0.054/100 000, showing a dynamic fluctuation trend(AAPC=-3.3, t=-0.3, P>0.05). The cases were mainly concentrated in Baoji, Hanzhong and Xi′an, accounting for 78.68%. The incidence peak was from May to October, accounting for 64.21% of annual incidence. The epidemic season was from May to October and December. The incidence of the disease was concentrated in the 40-69 age group, accounting for 58.88%, and the sex was 1.07:1. The main occupation was farmers, accounting for 72.08%. The median time from onset to diagnosis was 7 days. Global spatial autocorrelation analysis showed that there were significant spatial autocorrelations in 11 years from 2005 to 2023(P<0.05). Local spatial autocorrelation analysis detected a total of 43“high-high”clustering areas, mainly concentrated in Baoji City. Conclusions The overall incidence of typhus in Shaanxi Province showed a dynamic fluctuation trend, with notable seasonal and regional aggregation. The incidence of typhus was higher in middle-aged and elderly people in rural areas. Surveillance should be strengthened in typhus endemic areas in summer and autumn, and health education should be conducted for key population to form good health habits and reduce the incidence of typhus.

[摘 要] 目的：探讨环指蛋白8（RNF8）对子宫内膜癌（EC）细胞顺铂（CDDP）敏感性的影响及可能机制。方法：基于在线数据库分析RNF8在EC组织中的表达及拷贝数变异；采用慢病毒介导shRNA稳定敲低Ishikawa细胞中RNF8表达并进行CDDP处理，按sh-NC+溶剂对照、sh-RNF8+溶剂对照、sh-NC + CDDP、sh-RNF8 + CDDP分组处理，并设置sh-RNF8 + CDDP + KU60019抑制实验。采用CCK-8、克隆形成、Annexin V-FITC/PI流式细胞术、Hoechst 33258/PI染色、WB及γ-H2AX免疫荧光检测细胞活力、克隆形成、凋亡、DNA损伤累积及ATM/CHK2通路相关蛋白表达。结果：RNF8在EC组织和细胞中表达升高。RNF8敲低降低细胞存活率和IC50，抑制克隆形成，并进一步增强CDDP诱导的凋亡；同时BAX、Cleaved-Caspase-3和γ-H2AX表达升高，BCL-2、p-ATM、p-CHK2和RAD21表达降低。KU60019处理进一步促进DNA损伤累积和细胞凋亡，并降低细胞活力。结论：RNF8可能通过ATM/CHK2轴促进DNA损伤应答并降低EC细胞对CDDP的敏感性；敲低RNF8可增加DNA损伤累积并增强CDDP敏感性。

" Lijie and yellowish sweating" originates from the chapter on stroke and arthralgia diseases in Synopsis of Golden Chamber. Later generations typically interpret it as yellow fluid oozing from painful joints, a characteristic manifestation of arthralgia. In Western medicine, Lijie corresponds to diseases such as gouty arthritis, with its primary clinical manifestations being redness, swelling, heat, and painful joints, most often without yellow fluid discharge. Therefore, the interpretation of " Lijie and yellowish sweating" contradicts the clinical manifestations often observed in this disease. Thus, this article reinterprets the meaning of " Lijie and yellowish sweating" from the pathogenesis of " sweat exposure to water, as if water harms the heart" , combined with the viewpoints of other medical practitioners. Determining the meaning of " yellowish sweating" is crucial for understanding the pathogenesis of arthralgia and clarifying the relationship between arthralgia and yellowish sweating. ZHANG Zhongjing mentioned arthralgia and " yellowish sweating" together, not to differentiate between the two diseases but to emphasize the common pathogenesis of the two, namely, the cold and dampness injuring the heart, blood, and vessels. This paper proposes a new explanation of " Lijie and yellowish sweating" , which suggests that " yellowish sweating" is not confined to the joints but can be found all over the body. The pathogenesis of " Lijie and yellowish sweating" lies in the insufficiency of the liver and kidney and exogenous water dampness, leading to disharmony between nutrient qi and defensive qi and between yin and yang. Primary treatment should harmonize yingfen and weifen, as well as tonify and replenish the liver and kidney. The clinical selection of medicines can be considered Guizhi Decotion, a type of formula. The pathogenesis of " Lijie and yellowish sweating" is complex, and clinical treatment should be comprehensively considered to achieve the best therapeutic effect.

AIM: To investigate the impact of corneal fluorescein sodium(NaF)staining on the examination results of iTrace visual function analyzer(iTrace).METHODS: Prospective cohort study. Totally 100 patients(100 eyes)with ametropia who visited the outpatient department of Anhui Eye Hospital from April to November 2024 were recruited. They were divided into an experimental group and a control group, with 50 patients(50 eyes, and only the right eyes were selected for inclusion)in each group. In the experimental group, corneal staining was performed using fluorescein sodium staining test strips, while in the control group, 1 drop of 0.9% normal saline was instilled into the eyes. The iTrace examination was conducted before the intervention and at 5, 10, and 20 min after the intervention. The total corneal higher-order aberrations, spherical aberration, coma aberration, trefoil aberration, best sphere value(RO value), asphericity factor(Q value), and corneal vertical refractive power difference(IS value)at each time of examination were recorded and compared.RESULTS: There was no statistically significant difference in the baseline levels between the two groups(all P>0.05). Intra-group comparison revealed that the total higher-order aberrations, spherical aberration, coma aberration, and trefoil aberration measured 5 min after NaF staining in the experimental group were significantly increased compared with those before staining(all P<0.05). Inter-group comparison showed that the changes(differences from the baseline)in the total corneal higher-order aberrations, spherical aberration, coma aberration, and trefoil aberration measured by iTrace 5 min after the intervention in the experimental group were significantly greater than those in the control group(all P<0.05). There was no statistically significant difference in the changes(differences from the baseline)of various iTrace parameters measured at 10 and 20 min after the intervention between the two groups(all P>0.05). There was no statistical significance in the RO value, Q value, and IS value in the two groups(all P>0.05).CONCLUSION: Corneal NaF staining can cause a short-term increase in the wavefront aberration values(total corneal higher-order aberrations, spherical aberration, coma aberration, trefoil aberration)measured by iTrace, and it gradually disappears with the passage of time. However, it has no impact on the measurement of corneal topography parameters(RO value, Q value, IS value).

As the number of patients with compromised immune function increases and fungal resistance develops, so does the risk of contracting deadly fungi in humans. Both fungi and humans are eukaryotes, so identifying unique targets for antifungal drug development is difficult. In addition, the existing antifungal drugs are limited by toxicity, drug interaction and drug resistance in practical application, which leads to the increasing incidence and fatal rate of fungal infections. Therefore, it is urgent to develop new antifungal drugs. The semi-synthetic technology using microbial fermentation products from natural sources as lead compounds has become the most used method in structural modification of antifungal drugs due to its advantages of few reaction steps and easy operation. This paper will introduce the current status of natural antifungal drugs in clinical use, as well as the latest progress in the research and development of new semi-synthetic antifungal drugs, and summarize their mechanism of action, structural modifications, advantages and disadvantages, so as to provide reference for the subsequent development of new antifungal drugs.