Zhusha Anshenwan is a classical traditional Chinese medicine （TCM） formula originating from LI Dongyuan's Treatise on the Differentiation of Endogenous and Exogenous Injuries （Nei Wai Shang Bian Huo Lun） of the Jin-Yuan period. It is composed of five medicinal ingredients： Cinnabaris （Zhusha）， Coptidis Rhizoma （Huanglian）， Angelicae Sinensis Radix （Danggui）， Rehmanniae Radix （Shengdihuang）， and Glycyrrhizae Radix et Rhizoma （Gancao）. Under the guidance of TCM theory， this formula is used to treat syndromes of disturbed spirit， including insomnia， palpitations， and anxiety， caused by hyperactivity of heart fire and deficiency of Yin-blood， and it also exerts auxiliary anticonvulsant effects in epilepsy and related conditions. However， the potential neurotoxicity， hepatotoxicity， and nephrotoxicity of its monarch drug， Cinnabaris （mainly composed of mercuric sulfide， HgS）， together with the risk of in vivo accumulation， have rendered its clinical application controversial， and it has not yet been formally included in the Pharmacopoeia of the People's Republic of China. In addition， restrictions imposed by the Minamata Convention on Mercury have led to an increasing shortage of natural medicinal Cinnabaris resources， making the evaluation of the efficacy and safety of synthetic Cinnabaris particularly urgent. This contradiction highlights the complexity of safety evaluation for traditional medicines. Existing studies indicate that Zhusha Anshenwan exhibits definite pharmacological activities in calming the mind， improving sleep， and regulating emotional disorders. Moreover， other components of the formula may exert antagonistic effects on the toxicity of Cinnabaris， and reports of severe mercury poisoning caused by standardized clinical use of this prescription are extremely rare. Research suggests that other ingredients in the compound formula， such as Rehmanniae Radix， Coptidis Rhizoma， and Glycyrrhizae Radix et Rhizoma， may effectively alleviate the hepatorenal toxicity of Cinnabaris through mechanisms including modulation of the gut microbiota， formation of mercury complexes， and direct protection of target organs. This article aims to systematically review the progress in pharmacodynamic research on Zhusha Anshenwan， to explore its mechanisms of action in depth， and to analyze the toxicokinetic characteristics and safety risks of Cinnabaris， as well as the scientific connotations of toxicity reduction and efficacy enhancement achieved through compound compatibility. In addition， it compares Zhusha Anshenwan with other commonly used sedative formulas， with the aim of providing a scientific basis and forward-looking perspectives for the safe and rational application and in-depth development of this classical prescription in a modern context， and of emphasizing the important value of holistic research on TCM compound formulas in addressing the challenges of single-component toxicity.

OBJECTIVE To explore the improvement effect and potential mechanism of ginsenoside F1 （GF1） on allergic rhinitis （AR） rats based on the mitogen-activated protein kinase （MAPK）/signal transducer and activator of transcription 3 （STAT3） pathway. METHODS Male SD rats were divided into a control group （ n ＝15） and a modeling group （ n ＝55）. The AR rat model was established by basic sensitization with ovalbumin followed by local challenge. The successfully modeled rats were randomly assigned to the AR group， low-dose GF1 group [2.5 mg/（kg·d） ] ， high-dose GF1 group [5 mg/（kg·d） ] ， loratadine group （positive control， 1.5 mg/（kg·d） ] ， and high-dose GF1+MAPK activator group [5 mg/（kg·d） GF1+0.2 nmol C16-PAF ] ， with 10 rats in each group. Another 10 rats from the control group were randomly selected as the blank control group. Rats in each group received corresponding drug solutions or normal saline via intranasal instillation and/or oral gavage once daily for 28 consecutive days. After the final administration， AR symptoms were observed and rhinitis symptom scores were assessed. Histopathological changes of the nasal mucosa were examined. The number of inflammatory cells in nasal lavage fluid， serum levels of inflammatory cytokines [interleukin-4 （IL-4）， IL-17， interferon-γ （IFN-γ） ] and immunoglobulin E （IgE）， as well as the density of goblet cells， the number of mast cells， and the expression of MAPK/STAT3 pathway-related proteins in nasal mucosal tissues were measured. RESULTS Compared with the blank control group， the AR group exhibited marked pathological damage to the nasal mucosal epithelium， characterized by interstitial edema and inflammatory cell infiltration. The rhinitis symptom score， the number of macrophages， lymphocytes， eosinophils， neutrophils and mast cells， the density of goblet cells， the levels of IL-4， IL-17 and IgE， as well as the protein phosphorylation levels of p38 MAPK and STAT3 were significantly increased or elevated， while the level of IFN-γ was significantly decreased in the AR group （ P ＜0.05）. Compared with the AR group， all administration groups showed recovery of nasal mucosal epithelial pathological damage and significant improvements in all quantitative indicators， with the high-dose GF1 group and loratadine group showing more pronounced improvements than the low-dose GF1 group （ P ＜0.05）. C16-PAF significantly reversed the ameliorative effects of GF1 on all quantitative indicators （ P ＜0.05）. CONCLUSIONS GF1 can alleviate rhinitis symptoms in AR rats and inhibit inflammatory responses， which may be related to the inhibition of the MAPK/STAT3 pathway activation.

[摘 要] 目的：探讨叉头框K1（FOXK1）在喉鳞状细胞癌（LSCC）中的表达、临床意义及对细胞增殖、迁移、侵袭的影响，并阐明其分子机制。方法：RT-qPCR、免疫组化检测LSCC组织及LSCC细胞TU177中FOXK1表达，分析其与临床病理参数及预后的相关性；通过瞬时转染构建FOXK1过表达与敲低细胞模型，通过MTS法、克隆形成实验、划痕愈合实验和Transwell实验检测细胞恶性生物学行为的变化；采用RT-qPCR检测上皮-间充质转化（EMT）相关因子mRNA的表达；采用WB法检测PI3K/AKT信号通路相关蛋白的表达；结合生物信息学预测与功能回复实验，验证FOXK1对AKT2的调控作用。结果：FOXK1在LSCC组织及细胞中高表达（P < 0.01），且主要定位于细胞核；FOXK1高表达与较晚TNM分期相关（P < 0.05），且FOXK1高表达患者5年生存率较低（P < 0.05）；过表达FOXK1显著增强TU177细胞增殖、迁移与侵袭能力并诱导EMT（P < 0.01或P < 0.05），敲低FOXK1则产生相反的效应；FOXK1可上调AKT2表达并激活PI3K/AKT信号通路；敲低AKT2可部分逆转FOXK1过表达对细胞增殖、迁移、侵袭及EMT进程的促进作用（P < 0.01或P < 0.05）。结论：FOXK1在LSCC中高表达，与肿瘤进展及不良预后密切相关。FOXK1可能通过上调AKT2激活PI3K/AKT信号通路，诱导EMT，从而促进LSCC细胞的恶性生物学行为。

Abstract The prevention and control of myopia in children and adolescents has become a national health strategy in China, and its prevention and management are transitioning from experience driven approaches to precise and intelligent strategies. Understanding the role of artificial intelligence (AI) in myopia prevention and control can provide a foundation for a comprehensive myopia prevention and control system. AI, with its powerful capabilities in data analysis and pattern recognition, shows significant potential in myopia risk prediction, screening and diagnosis, intervention support and behavior monitoring in children and adolescents. The article systematically summarizes the scientific evidence and consensus on the application of AI for myopia prevention and control in children and adolescents. From the perspective of public health practice, it proposes hierarchical expert recommendations for multiple scenarios including schools, families, communities and medical institutions, as well as policy and research with development. Furthermore, it discusses current challenges and future directions, aiming to provide a reference for building an intelligent, precise and fully covered comprehensive myopia prevention and control system in children and adolescents.

To evaluate patient satisfaction levels in a gynecological teaching clinic and to explore its associated influencing factors, so as to provide evidence for optimizing the operational model of teaching clinics.

Collagen is a major structural protein in the matrix of animal cells and the most widely distributed and abundant functional protein in mammals. Collagen’s good biocompatibility, biodegradability and biological activity make it a very valuable biomaterial. According to the source of collagen, it can be broadly categorized into two types: one is animal collagen; the other is recombinant collagen. Animal collagen is mainly extracted and purified from animal connective tissues by chemical methods, such as acid, alkali and enzyme methods, etc. Recombinant collagen refers to collagen produced by gene splicing technology, where the amino acid sequence is first designed and improved according to one’s own needs, and the gene sequence of improved recombinant collagen is highly consistent with that of human beings, and then the designed gene sequence is cloned into the appropriate vector, and then transferred to the appropriate expression vector. The designed gene sequence is cloned into a suitable vector, and then transferred to a suitable expression system for full expression, and finally the target protein is obtained by extraction and purification technology. Recombinant collagen has excellent histocompatibility and water solubility, can be directly absorbed by the human body and participate in the construction of collagen, remodeling of the extracellular matrix, cell growth, wound healing and site filling, etc., which has demonstrated significant effects, and has become the focus of the development of modern biomedical materials. This paper firstly elaborates the structure, type, and tissue distribution of human collagen, as well as the associated genetic diseases of different types of collagen, then introduces the specific process of producing animal source collagen and recombinant collagen, explains the advantages of recombinant collagen production method, and then introduces the various systems of expressing recombinant collagen, as well as their advantages and disadvantages, and finally briefly introduces the application of animal collagen, focusing on the use of animal collagen in the development of biopharmaceutical materials. In terms of application, it focuses on the use of animal disease models exploring the application effects of recombinant collagen in wound hemostasis, wound repair, corneal therapy, female pelvic floor dysfunction (FPFD), vaginal atrophy (VA) and vaginal dryness, thin endometritis (TE), chronic endometritis (CE), bone tissue regeneration in vivo, cardiovascular diseases, breast cancer (BC) and anti-aging. The mechanism of action of recombinant collagen in the treatment of FPFD and CE was introduced, and the clinical application and curative effect of recombinant collagen in skin burn, skin wound, dermatitis, acne and menopausal urogenital syndrome (GSM) were summarized. From the exploratory studies and clinical applications, it is evident that recombinant collagen has demonstrated surprising effects in the treatment of all types of diseases, such as reducing inflammation, promoting cell proliferation, migration and adhesion, increasing collagen deposition, and remodeling the extracellular matrix. At the end of the review, the challenges faced by recombinant collagen are summarized: to develop new recombinant collagen types and dosage forms, to explore the mechanism of action of recombinant collagen, and to provide an outlook for the future development and application of recombinant collagen.

Objective To investigate the predictive value of temperature gradients on the mortality of sepsis patients and their correlation with fluid input.Methods By means of a prospective observational method,154 patients with sepsis or septic shock admitted to the Department of Critical Care Medicine at Nanfang Hospital,Southern Medical University from November 2019 to November 2021 were included as research subjects.They were divided into a survivor group(n=118)and a non-survivor group(n=36)according to whether they survived within 28 days.The core-to-toe temperature gradient(CTTG)and toe-to-room temperature gradient(TRTG)were monitored and calculated immediately upon admission to the intensive care unit(ICU)and 6 hours after admission.Receiver operating characteristic(ROC)curve was used to explore the predictive value of temperature gradients on mortality,and multivariate Cox regression analysis was performed to explore the risk factors of 28-day mortality in sepsis patients.The results were verified through survival analysis.Correlation analysis and multivariate analysis of variance were used to explore the correlation between temperature gradients and fluid input,as well as noradrenaline doses.Results Among the 154 patients,118 survived within 28 days(survivor group),and 36 died(non-survivor group).ROC curve and multivariate Cox regression analysis showed that a toe-to-room temperature gradient of≤5.35℃within 6 hours after admission was a risk factor for 28-day mortality.Compared with patients with a high toe-to-room temperature gradient(>5.35℃),patients with a low toe-to-room temperature gradient(≤5.35℃)had a 2.74-fold increase in the risk of 28-day mortality(P=0.004,95%CI 1.54,9.12).The CTTG and TRTG upon admission to the ICU and 6 hours after admission were not significantly associated with fluid input or noradrenaline doses(P>0.05).Conclusions A toe-to-room temperature gradient of less than or equal to 5.35℃within 6 hours after ICU admission is a risk factor for 28-day mortality in sepsis patients.The improvement of temperature gradients at different time points is not associated with fluid input.

Objective:To investigate the impact of early invasive arterial blood pressure (IBP) monitoring on survival and neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR).Methods:This retrospective cohort study analyzed 44 OHCA patients receiving ECPR between January 2021 and January 2023. Patients were divided into: Early intervention group : IBP established within 3 min of ECMO initiation; Late intervention group : IBP established after ICU admission. Baseline characteristics, ECMO parameters, and clinical outcomes were compared. Multivariable logistic regression (adjusted for age, initial rhythm, etc.) and Spearman's correlation were used.Results:This study included a total of 44 patients treated with OHCA and ECPR, divided into an early intervention group of 23 cases and a late intervention group of 21 cases. The early intervention group showed significantly higher: Survival to discharge (43.5% vs. 9.5%, P<0.05), Good neurological recovery (CPC 1-2: 34.8% vs. 9.5%, P<0.05).Early intervention independently predicted survival (adjusted OR=18.84, 95% CI:1.97-179.98, P=0.01). Stratified analysis by pH (cutoff 7.0) demonstrated consistent benefits in both pH>7.0 ( aOR=0.392, 95% CI:0.106-0.678) and pH≤7.0 subgroups ( aOR=0.385, 95% CI: 0.075-0.695; interaction P=0.183). Early IBP positively correlated with CPC scores ( ρ=0.40, P=0.007). Conclusions:Early IBP monitoring significantly improves survival and neurological outcomes in OHCA-ECPR patients, supporting its integration into standardized protocols.

OBJECTIVE: To analyze the clinical phenotype and genetic basis of four children with CHARGE syndrome. METHODS: A retrospective analysis was conducted on four children diagnosed with CHARGE syndrome at Xiamen Children's Hospital from May 2019 to May 2025. Peripheral venous blood samples were collected from the children and their parents and subjected to trio-whole exome sequencing. Candidate variants were verified by Sanger sequencing. Online tools were used for the conservation analysis and protein structure prediction. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2024-126). RESULTS: The four children have included two neonates, one infant and one child, with their age at the initial diagnosis ranging from 16 days after birth to 11 years old. Their initial manifestations were not typical of CHARGE syndrome. All children were found to harbor missense variants of the CHD7 gene, including c.3059T>C (p.L1020S), c.3302G>A (p.C1101Y), c.5879C>T (p.S1960F) and c.8093C>T (p.S2698L). Sanger sequencing confirmed that two were de novo variants, and two were inherited from their parents. In child 1, the leucine at position 1020 was highly conserved, and the p.L1020S variant did not alter the spatial structure and hydrogen bond connections of the CHD7 protein, though the shape of the binding cavity and the number and distribution of binding probe clusters have changed. In child 4, an unreported variant in the epilepsy gene SCN9A (c.2152T>C, p.Y718H) was detected, along with bilateral lower limb deformities. Literature review suggested that missense variants of the CHD7 gene were most common (32.1%) among the Chinese population, whilst nonsense variants had the highest lethality rate (41.2%) in neonates. CONCLUSION Variants of the CHD7 gene probably underlay the pathogenesis in the four children. Changes in the binding sites and binding cavity morphology play an important role in CHARGE syndrome. The types of genetic variants in CHARGE patients may vary between different regions and races.
Humans ; CHARGE Syndrome/genetics* ; Male ; Female ; Child ; Infant ; Infant, Newborn ; DNA Helicases/genetics* ; DNA-Binding Proteins/chemistry* ; Mutation, Missense ; Retrospective Studies ; Child, Preschool ; Exome Sequencing ; Phenotype

Objective:To analyze the association of apolipoprotein E(ApoE),soluble semaphoring 4D(sSema4D),and cyclophilin A(CypA)levels with unfavorable outcome in patients with chronic heart failure(CHF).Methods:We retrospectively enrolled 108 patients with CHF admitted in the Fifth Affiliated Hospital of Zhengzhou Universi-ty between March 2019 and March 2022.According to the outcome during 6-month follow-up,patients were di-vided into favorable outcome group(n=71)and unfavorable outcome group(n=37).ApoE,sSema4D and CypA levels were compared between the two groups,and multivariate Logistic regression was employed to identify the risk factors of unfavorable outcome within 6-month follow-up in CHF patients.Results:Compared to patients in the favorable outcome group,those in the unfavorable outcome group had significant higher proportion of NYHA classⅣ(59.46％vs.25.35％),serum creatinine[(80.74±3.89)μmol/L vs.(71.36±3.63)μmol/L],ApoE[(69.87±4.25)mg/L vs.(47.36±3.17)mg/L],sSema4D[(916.62±7.32)ng/L vs.(426.42±6.25)ng/L]and CypA[(6.74±1.32)ng/L vs.(4.38±0.72)ng/L](P＜0.001 all).Multivariate Logistic regression indicated that NY-HA class Ⅳ(OR=2.782,95％CI 1.166～6.636),serum creatinine(OR=29.893,95％CI 6.782～131.768),ApoE(OR=12.046,95％CI 4.694～30.913),sSema4D(OR=8.390,95％CI 2.260～31.146)and CypA(OR=6.486,95％CI 1.780～23.635)were independent risk factors for unfavorable outcome within 6-month follow-up in CHF patients(P＜0.05 or＜0.01).Conclusion:The levels of ApoE,sSema4D and CypA were closely associated with short-term unfavorable outcome in patients with chronic heart failure.