ObjectiveThis paper aims to observe the protective effect of Huamoyan granules on knee osteoarthritis （KOA） and explore whether its protective effect is oriented toward an anti-inflammatory direction by regulation of macrophage polarization， which can effectively inhibit the progression of pathological inflammatory response， reduce the release of inflammatory pain mediators， and downregulate the protein expression level of transient receptor potential vanilloid 1 （TRPV1）， so as to provide experimental evidence for its clinical application and investigate its action mechanism. MethodsAfter adaptive feeding， Sprague-Dawley （SD） rats were randomly divided into six groups： sham group， model group， celecoxib group， and high， medium， and low-dose synovitis granule groups （9.6， 4.8， 2.4 g·kg^-1）. The administration dose of celecoxib capsules was 20 mg·kg^-1. There were 10 rats in the sham group and 12 rats in the model group and each administration group. A KOA animal model was established by means of intra-articular injection of sodium iodoacetate into the knee joint. From the 10^th day of the experiment， each administration group was given intragastric administration at a dose of 10 mL·kg^-1 for 4 weeks. General conditions of rats in each group were assessed daily. The pressure pain threshold （PPT） to mechanical stimulation and joint diameter were recorded. X-ray examination was performed on the right knee joints of rats for imaging analysis. Enzyme linked immunosorbent assay （ELISA） was performed to detect the tumor necrosis factor-α （TNF-α）， serum interleukin-1β （IL-1β）， and other pro-inflammatory cytokines in rat serum samples， as well as the expression levels of neurogenic inflammatory mediators such as nerve growth factor （NGF） and calcitonin gene-related peptide （CGRP）. Histopathological changes in the knee joint synovial tissues were examined by hematoxylineosin （HE） staining. Safranin O-fast green staining was performed to observe and evaluate the degree of knee cartilage lesions. Western blot was employed to quantitatively analyze TRPV1， p38 mitogen-activated protein kinase （p38 MAPK）， and phosphorylated （p）-p38 MAPK in rat knee synovial tissues. Immunofluorescence （IF） was used to measure and assess M1/M2 macrophage polarization. ResultsCompared with those in the sham group， the circumference and joint diameter of the right knee were markedly enlarged in the model group （P<0.01）， while PPTs of rats showed a significant reduction （P<0.01）. The contents of IL-1β， TNF-α， CGRP， and NGF in rats' serum were significantly elevated （P<0.01）， and the synovial Krenn score was increased （P<0.01）. The Mankin score of cartilage tissue was increased （P<0.01）， and the protein expressions of TRPV1 and p-p38 MAPK/p38 MAPK were significantly upregulated （P<0.01）. The experimental intervention significantly reduced the proportion of pro-inflammatory M1 macrophages in the total macrophage population （P<0.01）， and the percentage of M2 macrophages was decreased （P<0.01）. The M1/M2 macrophage ratio was significantly elevated （P<0.01）. Knee joint diameters of all dose groups of Huamoyan granules and the celecoxib group were reduced （P<0.01） compared with those of the model group， and the PPT recovery speeds in the high and medium-dose groups of Huamoyan granules were more obvious （P<0.05）. The contents of IL-1β， CGRP， and NGF in the rats' serum in all administration groups were significantly reduced （P<0.05， P<0.01）， and the content of TNF-α in rats' serum was significantly reduced （P<0.01）. All dose groups of Huamoyan granules demonstrated significant reductions in both synovial Krenn score （P<0.05， P<0.01） and protein expression of TRPV1 and p-p38 MAPK/p38 MAPK in rats' synovial tissues （P<0.01）. The percentage of M1 macrophages in the synovial tissues of the celecoxib group and all dose groups of Huamoyan granules was decreased （P<0.01）. The percentage of M2 macrophages was increased （P<0.05）， and the M1/M2 ratio was decreased （P<0.01）. ConclusionHuamoyan granules can alleviate the inflammatory response of KOA， reduce the release of inflammatory pain mediators， and downregulate TRPV1 protein expression by regulating macrophage polarization. Its mechanism may be related to the TRPV1/p38 MAPK signaling pathway， thereby achieving the effect of improving peripheral pain hypersensitivity in KOA.

ObjectiveTo investigate the incidence and influencing factors of posttraumatic stress disorder （PTSD） three months after a traffic accident， and to explore the role of social support and coping strategies. MethodsA total of 117 individuals exposed to trauma following road traffic accidents were recruited. General demographic and clinical information was collected within one week， and the hamilton anxiety rating scale （HAMA）， the hamilton depression rating scale-24 （HAMD-24）， the social support rating scale （SSRS）， and the simplified coping style questionnaire （SCSQ） were administered. A 3-month follow-up was subsequently conducted， during which PTSD symptoms were assessed using the post-traumatic stress disorder checklist for DSM-5 （PCL-5）. Participants were divided into a PTSD group and a non-PTSD group according to whether PTSD occurred. Between-group comparisons were performed using the Mann-Whitney U non-parametric test or the χ² test， as appropriate. Spearman correlation analysis was used to examine the associations between general characteristics and PCL-5 scores. Binary Logistic regression was applied to identify factors influencing PTSD， and receiver operating characteristic （ROC） curve analysis was conducted to evaluate the diagnostic value of the SCSQ and SSRS. ResultsDuring the 3-month follow-up of the 117 trauma-exposed individuals， 17 cases developed PTSD， with a higher proportion of females （70.59%）. Between-group comparisons showed that， compared with the PTSD group， the non-PTSD group had higher scores for positive coping， objective support， and subjective support （P<0.05）， and lower scores for negative coping， HAMA， HAMD， and PCL-5 （P<0.05）. Correlation analysis indicated that female gender， negative coping， and higher HAMA and HAMD scores were associated with greater PTSD severity. Logistic regression analysis demonstrated that educational level （OR=1.715， 95% CI： 1.020-2.883， P=0.042） and negative coping （OR=1.590， 95% CI： 1.003-2.522， P=0.048） were risk factors for PTSD， whereas objective support （OR=0.646， 95% CI： 0.451-0.925， P=0.017） was a protective factor. The ROC analysis showed that the total SCSQ score and its negative and positive coping dimensions， the total SSRS score and its subjective and objective support dimensions， as well as their combined use， all demonstrated good discriminative ability in distinguishing between the PTSD and non-PTSD groups. ConclusionThe results suggest that individuals who are female， with higher HAMA and HAMD scores after a motor vehicle accident， and those with lower social support and negative coping strategies， should be given particular attention. Early interventions for these individuals may reduce the incidence of PTSD.

ObjectiveProtein-protein interactions (PPIs) are fundamental to the execution of biological functions within living cells. However, traditional biochemical methods, such as co-immunoprecipitation (Co-IP), often fail to capture transient, weak, or membrane-associated interactions due to the stringent detergent requirements for cell lysis. Proximity labeling (PL) has emerged in recent years as a transformative technology for mapping the proteomes of specific subcellular compartments and identifying dynamic interactomes in situ. Golgi protein 73 (GP73, also known as GOLPH2), a resident type II Golgi transmembrane protein, is a well-recognized clinical biomarker for liver diseases, including hepatocellular carcinoma (HCC). Despite its clinical significance, the comprehensive physiological and pathological functions of GP73 remain partially understood. This study aims to establish an APEX2-mediated proximity labeling system specifically targeting GP73 to map its interactome in a living cellular environment, thereby providing new insights into its molecular roles and regulatory mechanisms. MethodsTo achieve spatial specificity, we first constructed a stable cell line expressing a fusion protein consisting of GP73 and the engineered soybean peroxidase APEX2. The localization of the GP73-APEX2 fusion protein was validated to ensure it correctly targeted the Golgi apparatus. The proximity labeling reaction was initiated by incubating the cells with biotin-phenol (BP) for 30 min, followed by a brief (1 min) treatment with1 mmol/L hydrogen peroxide (H₂O₂). This catalytic reaction converts BP into highly reactive, short-lived biotin-phenoxyl radicals that covalently attach to endogenous proteins within a small labeling radius of the GP73-APEX2 enzyme. Subsequently, the cells were quenched, and biotinylated proteins were enriched using high-affinity streptavidin-coated magnetic beads. The captured “neighbor” proteins were subjected to on-bead digestion and analyzed via liquid chromatography-tandem mass spectrometry (LC-MS/MS) for high-throughput identification. Rigorous bioinformatics analysis, including Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction network mapping, was performed to interpret the biological significance of the identified candidates. ResultsOur results demonstrate the successful establishment of a robust and sensitive APEX2-based proximity labeling system for GP73. We identified a total of 95 high-confidence interacting proteins that were significantly enriched in the GP73 proximity proteome compared to control groups. Bioinformatics analysis revealed that these interactors were predominantly associated with biological processes such as vesicular transport, protein localization, and, most notably, molecular functions related to “ribosome binding” and “translation regulation”. This suggested an unexpected role for the Golgi-resident GP73 in the cellular translation machinery. To validate these findings, we performed targeted biochemical assays which confirmed a direct interaction between GP73 and the subunits of the eukaryotic translation initiation factor 3 (eIF3) complex, specifically EIF3G and EIF3I. Furthermore, functional validation using the surface sensing of translation (SUnSET) assay—a non-radioactive method to monitor protein synthesis—revealed that the overexpression of GP73 significantly promoted global protein translation levels in the cell, whereas its depletion or inhibition resulted in reduced translation efficiency. ConclusionThis study successfully utilized APEX2-mediated proximity labeling to provide the first systematic map of GP73 interactome in living cells. Our findings uncover a novel, unconventional function of GP73 as a regulator of cellular protein translation, likely mediated through its interaction with the eIF3 complex. This discovery significantly broadens our understanding of the biological roles of GP73 beyond its traditional function in the Golgi apparatus and suggests that it may act as a bridge between Golgi-related trafficking and the protein synthesis machinery. Furthermore, the technical framework established in this study provides a valuable template for investigating other complex organelle-associated protein networks and resolving transient macromolecular interactions in various physiological and pathological contexts.

Hepatic alveolar echinococcosis is a highly invasive zoonotic parasitic disease with poor prognosis. Surgical intervention serves as the pivotal approach to achieve radical cure and improve the prognosis of hepatic alveolar echinococcosis patients. In recent years, with the popularization of the concept of precision surgery and the development of the multidisciplinary diagnosis and treatment model, the surgical treatment strategies for hepatic alveolar echinococcosis have been continuously enriched, and the selection of surgical procedures has become increasingly diversified. Although key surgical techniques such as radical hepatectomy, autologous liver transplantation and allogeneic liver transplantation have achieved remarkable progress in clinical application, many insurmountable challenges still remain. Therefore, by sorting out the latest evidence-based advances in the field of surgical treatment for hepatic alveolar echinococcosis, this article focuses on discussing the application status and bottlenecks of radical hepatectomy, autologous liver transplantation and allogeneic liver transplantation in hepatic alveolar echinococcosis, aiming to provide a reference for the clinical treatment of hepatic alveolar echinococcosis.

ObjectiveTo investigate the role of interleukin （IL）-17A in acute inhalational pneumonia induced by the highly drug-resistant and hypervirulent Staphylococcus aureus strain USA300-R in mice. MethodsAn acute inhalational pneumonia model was established in mice using an aerosolized pulmonary delivery technique. RNA sequencing （RNA-seq） and enzyme-linked immunosorbent assay （ELISA） were employed to examine the expression dynamics of Il17a mRNA and IL-17A protein， respectively， in the lungs of infected mice. Il17a knockout （Il17a^-/-） mice were generated using CRISPR/Cas9 gene editing technology. The survival rate， body weight， bacterial load in lung tissue， and histopathological changes were compared between Il17a^-/- and wild-type （WT） mice following inhalational infection with USA300-R. Results12 hours after USA300-R infection， compared to pre-infection， the expression level of Il17a mRNA in lung tissue and the level of IL-17A protein in bronchoalveolar lavage fluid （BALF） increased by approximately 50-fold （P<0.01） and 6-fold （P<0.001）， respectively. Compared to WT mice， Il17a^-/- mice exhibited approximately 10-fold higher bacterial loads in lung tissue at both 12 and 24 hours post-infection （P<0.001， P<0.05）. However， they showed significantly attenuated lung histopathological injury， reduced alveolar wall thickening， markedly decreased neutrophil infiltration， and an approximately 50% improvement in survival rate （P<0.05）. ConclusionIn acute Staphylococcus aureus USA300-R inhalational pneumonia， IL-17A contributes to bacterial clearance by recruiting neutrophils； however， excessive neutrophil infiltration exacerbates pulmonary inflammation and injury， reduces survival rates， and represents a potential therapeutic target.

ObjectiveTo analyze the risk factors for long-term cardiovascular events in patients undergoing long-term peritoneal dialysis （PD）， and to construct and validate a visual nomogram prediction model based on multiple parameters. MethodsA prospective cohort study was conducted， consecutively enrolling 248 maintenance PD patients （dialysis duration ≥ 3 months）. Demographic characteristics， clinical indicators， laboratory parameters， and echocardiographic indices （including left ventricular ejection fraction ［LVEF］， ratio of early diastolic mitral inflow velocity to early diastolic mitral annular velocity （E/e’）， etc.） were collected. The composite endpoint was defined as the occurrence of cardiovascular events or cardiovascular death， with non-cardiovascular death as the competing risk and loss to follow-up or the end of follow-up as censoring events. Fine-Gray competing risks model was used to screen independent predictors， based on which a nomogram model was constructed. Internal validation was performed using the Bootstrap method （1 000 resamplings）， and the concordance index （C-index） and time-dependent receiver operating characteristic （time-dependent ROC） curve were calculated to evaluate the model performance. ResultsWith a median follow-up of 29 months （interquartile range： 24–35 months）， 88 patients （35.48%） reached the composite endpoint， including 80 cases of cardiovascular events and 8 cases of cardiovascular death， and 4 patients died of non-cardiovascular causes. Multivariate Fine-Gray analysis revealed that age， diabetes mellitus， hemoglobin （HGB） level and E/e' ratio were independent influencing factors of the composite endpoint. Specifically， each 1-year increase in age was associated with a 3.0% increase in the risk of the composite endpoint （HR=1.030， P=0.006）； patients with diabetes mellitus had a 167.9% higher risk compared with non-diabetic patients （HR=2.679， P=0.007）； each 1g/L increase in HGB level contributed to a 1.5% reduction in the risk （HR=0.985， P=0.003）； and each 0.1 increase in E/e' ratio led to a 7.2% increase in the risk （HR=1.072， P=0.045）. The nomogram model had a C-index of 0.76 （95% CI： 0.698–0.820）， and the AUC of the time-dependent ROC curve reached 0.849 at 23 months of follow-up. ConclusionIncreased age， complicated with diabetes mellitus， decreased HGB， and elevated E/e' ratio are independent risk factors of long-term occurrence of cardiovascular events and cardiovascular death in patients undergoing long-term PD. The nomogram model constructed based on the above variables has good predictive value and clinical applicability， which can provide a reference for cardiovascular risk stratification and individualized intervention in long-term PD patients.

By consulting herbal texts， medical records， formula collections， and other relevant literature from various historical periods， as well as modern and contemporary research materials， different aspects of the historical evolution of Zijingpi， including its name， origin， scientific name verification， medicinal part， genuine producing areas， harvesting， processing， and preparation， properties and flavors， and primary indications， were systematically reviewed and verified， providing a basis for the development of famous classical formula preparations containing this medicinal material. According to the textual research， Cercis chinensis was first recorded under the name "Zijingmu" in the Rihuazi Bencao from the Five Dynasties period. From the Song Dynasty to the Qing Dynasty， it was known by various names such as "Zijing"， "Zijingpi"， and "Zijingmupi". In modern and contemporary times， it has been officially named "Zijingpi"， with aliases such as "Mantiaohong"， "Zihuashu"， and "Qingminghua". Historically， the mainstream source of Zijingpi was the dried bark of Cercis chinensis Bunge， a species of the legume family. However， there were also instances of confusion with the Lythraceae plant Lagerstroemia indica L. The producing areas of Zijingpi have no special geographical limitation， and the plant is currently distributed throughout most parts of China. There were no special requirements for harvesting time in ancient times， while modern records indicate harvesting time in spring， summer， and autumn. Ancient processing methods were rarely recorded， with only mentions of stir-frying Zijingpi. Modern practice mostly uses the raw material medicinally. Modern standards prefer it to be "dry， long strips， and thick". The functions of Zijingpi， mainly to promote blood circulation， relieve strangury， and detoxify， have remained consistent from ancient to modern times. Based on the textual research findings， it is recommended that when developing and exploiting the famous classical formulas containing Zijingpi， the bark of C. chinensis should be selected as the source. The processing method should be chosen according to the formula requirements， and if no specific requirements are indicated， it is suggested to use the raw material medicinally.

low transit constipation （STC） is a common functional intestinal disorder caused by impaired colonic transit function， characterized by reduced bowel movement frequency， hard stools， and difficulty in defecation. The mitogen-activated protein kinase （MAPK） signaling pathway， which mainly includes extracellular signal-regulated kinase （ERK）， c-Jun N-terminal kinase （JNK）， and p38 subtypes， plays a critical regulatory role in the occurrence and development of STC. This paper systematically reviews the multiple pathogenic mechanisms of the MAPK signaling pathway in STC and the research progress of traditional Chinese medicine （TCM） intervention.At the mechanistic level， the MAPK signaling pathway promotes the progression of STC through the following links：（1） Activation of p38 upregulates the expression of aquaporin 3 （AQP3）/AQP4 in the colon， leading to excessive reabsorption of water in the intestinal lumen； （2） It forms a positive feedback loop with nuclear factor-κB （NF-κB） to maintain low-grade intestinal inflammation， releases inflammatory factors such as tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）， and inhibits smooth muscle contraction； （3） Overactivation of p38 downregulates the expression of occludin and mucin 2 while upregulates the expression of claudin-2， thereby disrupting the mucosal barrier； （4） The JNK/p38 signaling pathway activates the caspase cascade to induce apoptosis of intestinal epithelial cells， neurons， and interstitial cells of Cajal； （5） Abnormal ERK signaling and excessive activation of p38/JNK inhibit intestinal smooth muscle contraction and reduce 5-hydroxytryptamine secretion， ultimately resulting in impaired colonic transit function.At the intervention level， TCM compound formulas and single herbs have been proven to improve STC by regulating the MAPK signaling pathway. Their effects are syndrome type-dependent：yin-nourishing formulas （Zengye Chengqi Tang， Tongbian Tang） mainly regulate the ERK/AQP axis； yang-warming formulas （Jichuan Jian） target both ERK/JNK and anti-apoptosis； heat-clearing formulas （Sanren Tang） focus on p38/NF-κB anti-inflammation. A single drug can simultaneously cover multiple aspects including water metabolism， inflammation， barrier function， apoptosis， and intestinal motility.Current relevant studies still have limitations such as mechanisms mostly remaining at the correlational level and a lack of disease-syndrome integrated research models. Future studies should combine specific inhibitors or gene knockout to identify core targets， establish disease-syndrome integrated STC models， and use network pharmacology and molecular docking techniques to deeply analyze the fine mechanism of “component-target-phenotype”， so as to provide high-quality evidence for the precise regulation of the MAPK signaling pathway by TCM in the intervention of STC.

Osteoporosis is a common senile bone metabolism disease， clinically characterized by decreased bone mass， destruction of bone microstructure， increased bone fragility， and easy fracture. It tends to occur in the elderly and postmenopausal women， seriously threatening the quality of life and physical and mental health of the elderly. At present， the treatment of osteoporosis is mainly based on oral western medicines， such as calcium， Vitamin D， and bisphosphonates. Still， there are drawbacks such as a long medication cycle and many adverse reactions. In recent years， due to the advantages of multi-component， multi-pathway， and multi-target， some traditional Chinese medicines and effective ingredients can regulate the osteogenic and osteoclastic differentiation process in both directions and are widely used in the prevention and treatment of osteoporosis. Hippophae rhamnoides is a commonly used herbal medicine， and its fruits are rich in flavonoids， polyphenols， fatty acids， vitamins， and trace elements， which have been proven to have a good anti-osteoporosis effect. Isorhamnetin is the main effective ingredient of Hippophae rhamnoides fruits， which has many pharmacological effects such as anti-inflammation， anti-oxidative stress， anti-aging， and anti-tumor. Studies have shown that isorhamnetin can participate in the regulation of bone metabolism and has a good anti-osteoporosis effect. However， the pharmacological effects and related mechanisms of isorhamnetin against osteoporosis have not been systematically summarized. Therefore， this paper reviewed the pharmacological effects and related mechanisms of isorhamnetin against osteoporosis by referring to relevant literature to provide more basis for the development and application of isorhamnetin.

ObjectiveTo explore the possible mechanisms of Modified Shoutai Pill （寿胎丸加味方， MSP） in treating polycystic ovary syndrome （PCOS） with hyperandrogenism， insulin resistance， and miscarriage， focusing on inflammatory response and endometrial receptivity. MethodsThirty female SPF-grade SD rats with regular estrous cycles and in proestrus， and 15 male SPF-grade SD rats were housed together in a 2∶1 ratio at 18：00. At 8：00 next morning， rats showing abundant sperm and vaginal plugs were considered pregnant on the day 0.5. The 30 pregnant rats were randomly divided into three groups， normal group， model group， and MSP group， with 10 rats in each group. From day 0.5 to day 13.5 of pregnancy， the MSP group was given 26.6 g/（kg·d） of the MSP via gavage twice a day for 14 consecutive days. The normal group and the model group received 4 ml of normal saline daily. From day 7.5 to day 13.5 of pregnancy， the rats in the model group and MSP group were intraperitoneally injected with dihydrotestosterone （DHT） and insulin （INS） for 7 consecutive days to establish a PCOS model with hyperandrogenism， insulin resistance， and miscarriage. On day 13.5 of pregnancy， an oral glucose tolerance test （OGTT） was performed to measure blood glucose levels at 0， 30， 60， 90， and 120 minutes. On day 14.5， serum level of progesterone （P₄）， estradiol （E₂）， fasting insulin （FINS）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α） were measured by ELISA. The insulin resistance index （HOMA-IR） was calculated. Embryo implantation， miscarriage rate， and average number of live fetuses were observed. Uterine tissue pathology was examined by HE staining， and mRNA expression of Il-6， Tnf-α， leukemia inhibitory factor （Lif）， homeobox gene 10 （Hoxa10）， prolactin family 8 subfamily A member 2 （Prl8a2）， and insulin-like growth factor-binding protein 1 （Igfbp1） in the uterine tissue was detected by qRT-PCR. ResultsCompared with the normal group， the model group had significantly higher blood glucose level at 0， 30， 60， 90， and 120 minutes， increased miscarriage rate， elevated HOMA-IR， decreased average number of live fetuses， lower level of P₄ and E₂， higher level of IL-6， TNF-α， and FINS， and higher mRNA expression of Il-6 and Tnf-α in the uterine tissue. The mRNA expression of Lif， Hoxa10， and Prl8a2 was reduced （P＜0.05 or P＜0.01）. The uterus had a dark red color， visible areas of bleeding， fewer embryos with developmental abnormalities， and increased placental necrosis. Pathological examination revealed thrombus in the decidual layer， unclear decidual cell morphology， loose arrangement， scattered distribution， edema degeneration in the cytoplasm， and nuclear shrinkage or disappearance， with extensive infiltration of inflammatory cells. In contrast， compared with the model group， the MSP group showed significantly lower blood glucose level at 0， 30， 60， 90， and 120 min， reduced miscarriage rate， lower HOMA-IR， increased number of live fetuses， higher level of P₄ and E₂， and lower level of IL-6， TNF-α， and FINS. The mRNA expression of Il-6 and Tnf-α in the uterine tissue was lower， while the expression of Lif， Hoxa10， and Prl8a2 mRNA was higher （P＜0.05 or P＜0.01）. There was significant improvement in uterine and embryo conditions， as well as in uterine tissue pathology. ConclusionThe MSP can reduce the miscarriage rate in a PCOS model with hyperandrogenism， insulin resistance， and miscarriage. Its mechanism may involve inhibiting inflammation， improving endometrial receptivity， and restoring the defects in endometrial decidualization.