ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis （AS）. MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group， low drug-containing serum group， medium drug-containing serum group， high drug-containing serum group， and positive drug group. After drug intervention， cell proliferation was measured using the cell counting kit-8 （CCK-8） assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase （ALP） activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin （OCN）， osteopontin （OPN）， and runt-related transcription factor 2 （Runx2） was detected by Western blot. The mRNA expression levels of Wnt5a， β-catenin， and Dickkopf-1 （DKK-1） were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression （P<0.05）. The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression （P<0.05， P<0.01）， with the positive drug group showing the most pronounced effect （P<0.01）. The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins （P<0.05， P<0.01）， while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN， OPN， and Runx2 proteins （P<0.05， P<0.01）. ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts， thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression， further inhibiting the transcription of downstream target genes.

The development of traditional Chinese medicine (TCM) diagnosis and treatment has undergone multiple paradigms, evolving from sporadic experiential practices to systematic approaches in syndrome differentiation and treatment and further integration of disease and syndrome frameworks. TCM is a vital component of the medical system, valued alongside Western medicine. Treatment based on syndrome differentiation embodies both personalized treatment and holistic approaches; however, the inconsistency and lack of stability in syndrome differentiation limit clinical efficacy. The existing integration of diseases and syndromes primarily relies on patchwork and embedded systems, where the full advantages of synergy between Chinese and Western medicine are not fully realized. Recently, driven by the development of diagnosis and treatment concepts and advances in analytical technology, Western medicine has been rapidly transforming from a traditional biological model to a precision medicine model. TCM faces a similar need to progress beyond traditional syndrome differentiation and disease-syndrome integration toward a more precise diagnosis and treatment paradigm. Unlike the micro-level precision trend of Western medicine, precision diagnosis and treatment in TCM is primarily reflected in data-driven applications that incorporate information at various levels, including precise syndrome differentiation, medication, disease management, and efficacy evaluation. The current priority is to accelerate the development of TCM precision diagnosis and treatment technology platforms and advance discipline construction in this area.

POEMS syndrome is a rare condition associated with plasma cell disorders， and it often involves multiple systems and has diverse clinical manifestations. This article reports two cases of POEMS syndrome with hepatosplenomegaly as the initial manifestation. During the course of the disease， the patients presented with lower limb weakness， hepatosplenomegaly， lymph node enlargement， ascites， hypothyroidism， positive M protein， and skin hyperpigmentation， and ¹⁸F-FDG PET-CT imaging revealed bone lesions mainly characterized by osteolytic changes and plasma cell tumors. There was an increase in the serum level of vascular endothelial growth factor. The patients were finally diagnosed with POEMS syndrome， and the symptoms were relieved after immunomodulatory treatment.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

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.

Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.

Anti-tumor drug research and development in non-small cell lung cancer (NSCLC) is rapidly developing, and the clinical application of high-throughput sequencing technology is also becoming widespread. Accordingly, researchers are focusing on human epidermal growth factor receptor-2 (HER-2) gene as a rare target of NSCLC, and a series of exploratory studies has been performed. Traditional chemotherapy and immunotherapy are unsatisfactory in the HER-2 mutant population, whereas the survival improvement of anti-HER-2 monoclonal antibodies and pan-HER inhibitors is limited. The development of antibody drug conjugate (ADC) ushers in a turning point for HER-2-mutated NSCLC, and new ADC drugs represented by trastuzumab deruxtecan are making a breakthrough. It opens up a new era of precision therapy for advanced HER-2-mutated NSCLC. Additionally, novel HER-2 inhibitors show very encouraging initial efficacy and safety, and clinical trials are ongoing. This review focuses on the latest progress of research on HER-2-mutated NSCLC.

ObjectiveTo investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis， and to establish a predictive model. MethodsA total of 217 patients who were diagnosed with decompensated hepatitis C cirrhosis and were admitted to The Third People’s Hospital of Kunming l from January， 2019 to December， 2022 were enrolled， among whom 63 patients who were readmitted within at least 1 year and had no portal hypertension-related complications were enrolled as recompensation group， and 154 patients without recompensation were enrolled as control group. Related clinical data were collected， and univariate and multivariate analyses were performed for the factors that may affect the occurrence of recompensation. The independent-samples t test was used for comparison of normally distributed measurement data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed measurement data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A binary Logistic regression analysis was used to investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis， and the receiver operating characteristic （ROC） curve was used to assess the predictive performance of the model. ResultsAmong the 217 patients with decompensated hepatitis C cirrhosis， 63 （29.03%） had recompensation. There were significant differences between the recompensation group and the control group in HIV history （χ²=4.566， P=0.034）， history of partial splenic embolism （χ²=6.687， P=0.014）， Child-Pugh classification （χ²=11.978， P=0.003）， grade of ascites （χ²=14.229， P<0.001）， albumin （t=4.063， P<0.001）， prealbumin （Z=-3.077， P=0.002）， high-density lipoprotein （t=2.854， P=0.011）， high-sensitivity C-reactive protein （Z=-2.447， P=0.014）， prothrombin time （Z=-2.441， P=0.015）， carcinoembryonic antigen （Z=-2.113， P=0.035）， alpha-fetoprotein （AFP） （Z=-2.063， P=0.039）， CA125 （Z=-2.270， P=0.023）， TT3 （Z=-3.304， P<0.001）， TT4 （Z=-2.221， P=0.026）， CD45⁺ （Z=-2.278， P=0.023）， interleukin-5 （Z=-2.845， P=0.004）， tumor necrosis factor-α （Z=-2.176， P=0.030）， and portal vein width （Z=-5.283， P=0.005）. The multivariate analysis showed that history of partial splenic embolism （odds ratio ［OR］=3.064， P=0.049）， HIV history （OR=0.195， P=0.027）， a small amount of ascites （OR=3.390， P=0.017）， AFP （OR=1.003， P=0.004）， and portal vein width （OR=0.600， P<0.001） were independent influencing factors for the occurrence of recompensation in patients with decompensated hepatitis C cirrhosis. The ROC curve analysis showed that HIV history， grade of ascites， history of partial splenic embolism， AFP， portal vein width， and the combined predictive model of these indices had an area under the ROC curve of 0.556， 0.641， 0.560， 0.589， 0.745， and 0.817， respectively. ConclusionFor patients with decompensated hepatitis C cirrhosis， those with a history of partial splenic embolism， a small amount of ascites， and an increase in AFP level are more likely to experience recompensation， while those with a history of HIV and an increase in portal vein width are less likely to experience recompensation.

ObjectiveTo investigate the role and mechanism of action of paeoniflorin （PF） in protecting HepG2 cells induced by palmitic acid （PA）. MethodsHepG2 cells were stimulated with PA at a concentration of 250 μmol/L to establish a NAFLD model. Compound C at a concentration of 10 μmol/L was used as an inhibitor， and PF at a concentration of 25 μmol/L was used for intervention. The experiment was divided into normal group （CON group） treated with complete culture medium， model group （MOD group） treated with PA， PF treatment group （MOD+PF group） treated with PA and PF， model+inhibitor group （MOD+COM group） treated with PA and Compound C， and model+inhibitor+PF group （MOD+COM+PF group） treated with PA， Compound C， and PF. Kits were used to measure lipid deposition indicators， liver function parameters， oxidative stress indicators， and inflammation indicators； oil red O staining was used to observe lipid deposition； Western Blot was used to measure the protein expression levels of AMPK， SIRT1， PGC-1α， mTOR， Beclin-1， LC3， and P62 in cells. The one-way analysis of variance was used for comparison of quantitative data between groups， while the Tukey’s test was used for comparison between two groups. ResultsCompared with the MOD group， PF improved the levels of TC and TG （P<0.05）， reduced the levels of ALT， AST， CRP， TNF-α， IL-1β， and IL-6 （P<0.05）， increased the activity of SOD and CAT and the level of GSH， and reduced the level of MDA in cells （all P<0.05）. Oil red O staining showed that PF alleviated lipid deposition in cells. Western blot results showed that compared with the MOD group， PF increased the protein expression levels of p-AMPK， SIRT1， PGC-1α， LC3Ⅱ/LC3Ⅰ， and Beclin-1 and reduced the protein expression levels of p-mTOR and P62 （all P<0.05）. ConclusionPF can inhibit PA-induced oxidative stress and inflammatory response in HepG2 cells， improve lipid deposition， and promote autophagy via the AMPK/SIRT1/PGC-1α/mTOR signaling pathway.