ObjectiveThis paper aims to investigate the protective effects of the Tanyu Tongzhi Youhua prescription（TYTZP） against myocardial ischemia/reperfusion injury in rats via regulation of the cyclic GMP-AMP synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodsFifty-six 8-week-old male Sprague-Dawley （SD） rats were randomly divided into sham group， model group， ticagrelor group （32.4 mg·kg^-1）， RU320521 （RU.521cGAS inhibitors） group （5 mL·kg^-1）， groups of TYTZP with low dose （3.6 g·kg^-1）， medium dose （7.2 g·kg^-1）， and high dose （14.4 g·kg^-1）， with eight rats per group. The ticagrelor group and groups of TYTZP with different doses received pre-treatment for seven days according to their respective protocols. The RU.521 group received an intraperitoneal injection one hour before modeling. A rat model of the no-reflow phenomenon in myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery in situ. Myocardial no-reflow area was determined by thioflavin staining. Histopathological morphology of myocardial tissue was observed via hematoxylin and eosin （HE） staining. Cardiac function was detected by echocardiography. Myocardial microcirculation function change was observed by using real-time myocardial contrast echocardiography. The myocardial enzyme levels in the serum were measured by serum biochemical analysis. The double-stranded DNA （dsDNA） levels were detected by using PicoGreen. The protein expression of cGAS， STING， and nuclear factor-κB （NF-κB） p65 in myocardial tissue was detected by Western blot. The levels of cardiac troponin Ⅰ （cTNⅠ）， cardiac troponin T （cTNT）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the peripheral blood were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham group， the model group showed a significantly increased myocardial no-reflow area （P<0.01）. Myocardial fiber rupture and disarray and inflammatory cell infiltration were observed by HE staining. The ultrasound results indicated that left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01） were significantly decreased. Real-time myocardial contrast echocardiography showed that the peak time of myocardial blood perfusion was significantly prolonged （P<0.01）， and the levels of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， cTNⅠ， cTNT， and dsDNA were significantly elevated （P<0.01）. Western blot results showed that the myocardial protein expressions of cGAS， STING， and NF-κB p65 were upregulated （P<0.01）. ELISA results showed that the inflammatory factors in the serum such as IL-6， IL-1β， and TNF-α were increased （P<0.01）. Compared with the model group， the group of the TYTZP significantly reduced the levels of myocardial enzyme， troponins， and dsDNA （P<0.01， P<0.05）， improved cardiac function and myocardial microcirculation， alleviated histopathological morphology and inflammatory infiltration， inhibited activation of the cGAS/STING pathway， reduced the expression of NF-κB p65 （P<0.01， P<0.05）， and inhibited inflammatory response. ConclusionThe TYTZP mitigates the no-reflow phenomenon in myocardial ischemia/reperfusion injury， and its mechanism is associated with inhibiting the activation of the cGAS/STING pathway and attenuating inflammatory responses.

ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

ObjectiveGastrodia elata has evolved ecological types with shortened rhizome internodes and diversified flower and fruit coloration in response to different altitudes. Studying the genetic mechanisms of different ecotype germplasm is significant for guiding variety breeding in different cultivation areas. MethodsThe bHLH gene family was identified based on the whole-genome datasets of G. elata f. elata and G. elata f. glauca. Subsequently， the gene family members were subject to analysis， including gene structure， chromosomal localization， cis-acting elements， gene synteny， and phylogeny. Combined with transcriptome data and quantitative Real-time PCR， the expression patterns of bHLH genes in the stems of the different G. elata ecotype germplasm were analyzed. Finally， correlation analysis was conducted between gene expression patterns and color to obtain the key bHLH genes regulating the color formation of stem. ResultsA total of 63 bHLH genes were identified in both G elata f. elata and G. elata f. glauca， unevenly distributed across 17 chromosomes and clustered into 16 subfamilies， with significant expansion in some family members. Obvious inversions of bHLH genes on the same chromosome and interchromosomal translocations were detected in the two ecotype germplasm. Among these genes， 12 bHLH genes （such as bHLH62-3 and bHLH74） were associated with the bright yellow color of G elata f. elata stem， while 9 bHLH genes （such as PIL13， UNE12， and bHLH130） were correlated with the red color of G. elata f. glauca stem. Compared to G. elata f. glauca， the bHLH48 expression level was significantly higher in flowers and scale leaves of G elata f. elata， and the bHLH62-3 expression level was significantly higher in all organs of G elata f. elata. ConclusionsFunctional pathway divergence of the bHLH family members has occurred across different chromosomes in G elata f. elata and G. elata f. glauca. Through synergism or antagonism with other genes， 21 bHLH genes participate in the coloration metabolic pathway regulation of stems， flowers， and fruits. Specifically， bHLH62-3 is involved in regulating stem color differentiation in the anthocyanin biosynthesis pathway of G. elata， thus relevant to the color formation of stem. Additionally， GebHLH48 positively regulates flowering-related pathways to promote the early-flowering phenotype of G. elata f. elata. These findings have laid the foundation for analyzing the genetic regulatory mechanisms underlying the color formation of the G. elata stem.

Bone metastasis is one of the common complications of lung cancer, which seriously affects the quality of life and survival of patients. At present, the clinical diagnosis of bone metastasis of lung cancer mainly depends on imaging methods, but due to its lack of sensitivity and potential radiation risk, about half of patients have already had bone-related events when they are diagnosed clearly. The treatment of bone metastasis of lung cancer mainly depends on surgery, radiotherapy and chemotherapy, targeted therapy, immunotherapy, etc. Although the treatment of bone metastasis of lung cancer has made some progress in recent years, there are still some problems such as high risk of other distant metastasis. This article mainly reviews the pathogenesis, diagnostic biomarkers and treatment progress of bone metastasis of lung cancer, in order to provide reference for the diagnosis and treatment of bone metastasis of lung cancer.

[摘 要] 目的：建立一种以乙型肝炎病毒核心蛋白（HBc）病毒样颗粒（VLP）为骨架，嵌合PD-1 B细胞表位的重组颗粒蛋白，研究其对小鼠结直肠癌（CRC）的抑制效果。方法：设计PD-1 HBc VLP质粒并导入BL21（DE3）获得重组PD-1 HBc VLP表达菌株后，通过优化培养温度，实现蛋白可溶性表达，经硫酸铵沉淀、Sepharose 4 Fast Flow尺寸排阻层析和DEAE阴离子树脂层析纯化获得高纯度的PD-1 HBc VLP。采用电泳、WB、HPLC及电镜手段对其表达水平、蛋白纯度、颗粒形成率、形态特征及抗原结合活性等特征进行系统表征，ELISA测定免疫小鼠后的血清效价，评价其免疫原性，构建CT26细胞CRC小鼠移植瘤模型，通过监测PD-1 HBc VLP治疗后小鼠体质量和肿瘤体积变化，评估PD-1 HBc VLP抗肿瘤活性。结果：在28 ℃条件下，可溶性目的蛋白表达量占总蛋白的10.27%，多步纯化后目的蛋白纯度为（91.77 ± 0.62）%，分子量为23 000，电镜测定粒径为（31.90 ± 1.88） nm，粒径仪测定粒径为（30.66 ± 0.62） nm，多分散指数（PDI）为（0.18 ± 0.05）。WB结果显示，PD-1 HBc VLP重组蛋白可分别与HBc VLP抗血清和PD-1抗体结合。ELISA结果显示，经PD-1 HBc VLP 3次免疫后，第14天小鼠血清中总抗体效价为1∶640 000，其中抗PD-1的效价为1∶40 000。抗肿瘤实验表明，PD-1 HBc VLP组小鼠的肿瘤抑制率为（27.99 ± 2.98）%，对照组在45 d全部死亡，PD-1 HBc VLP组中位生存期延长20 d。结论：成功制备了以HBc VLP为骨架，嵌合PD-1 B细胞表位的PD-1 HBc VLP，且对小鼠结直肠癌有治疗效果。

Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory disease around the world, and pharmacotherapy is the foremost treatment method currently. In recent decades, with the rapid development of bronchoscopic interventional therapy, endoscopic physical ablation technology presents a therapeutic effect in treating COPD, with few treatment-related side effects, showing excellent application prospects in treating COPD. Since ablation techniques in this field are emerging technologies with low patient acceptance, they are not widely used in the clinical treatment of COPD. This article reviews the development process of physical ablation techniques. Moreover, their current application status and the prospects in the field of COPD treatment are also summarized and analyzed. We hope to promote the application of physical ablation in the clinical treatment of COPD and provide practical references and a theoretical basis for the clinical treatment of COPD.

ObjectiveThis study aims to investigate the effectiveness and mechanisms of Polygonati Rhizoma polysaccharides （PRP） on improving cognitive and emotional functions in the ovariectomy （OVX）-Alzheimer's disease （AD） model rats. MethodsAfter being randomly divided into blank group， model group， estradiol group （0.18 mg·kg^-1·d^-1）， low-PRP group （200 mg·kg^-1）， medium-PRP group （400 mg·kg^-1）， and high-PRP group （800 mg·kg^-1）， 60 SPF female Sprague-Dawley （SD） rats were subjected to OVX. One week later， vaginal smear examination as well as D-galactose intraperitoneal injection （150 mg·kg^-1·d^-1， once daily， for eight weeks） were adopted to establish the OVX-AD model， and drug intervention was initiated nine weeks after surgery. Upon completion of the treatment course， cognitive and emotional functions， as well as hippocampal CA3 region damage were assessed in all rats by open-field test， new object recognition test， Morris water maze test， and transmission electron microscopy. Indicators of inflammation ［interleukin-6 （IL-6）， tumor-necrosis-factor-α （TNF-α）， interleukin-1β （IL-1β））， oxidative-stress （superoxide-dismutase （SOD）， glutathione-peroxidase （GSH-Px）］ were measured by enzyme-linked immunosorbent assay （ELISA） and biochemical methods. The mRNA and protein expression levels of estrogen-receptor α （ERα）/phosphoinositide 3kinase （PI3K）/protein-kinase-B （Akt） signaling pathway， apoptosis ［Bcl-2 associated X protein （Bax）， B-cell lymphoma/leukemia-2 （Bcl-2）］ and the indicators of pathological sedimentary proteins ［amyloid β-protein_1-42 （Aβ_1-42）， microtubule-associated protein Tau， phosphorylated site 404 of microtubule-associated protein Tau ［p-Tau （Ser404）］ were detected by using real-time polymerase chain reaction （Real-time PCR） and western blot analysis. ResultsCompared with those in blank group， the rats in model group exhibited marked ultra-structural damage to hippocampal CA3 neurons， along with the reduction of activity time and shuttle frequency in central area， the index and exploration frequency of new object recognition， and the platform crossings and time spent in target quadrant， as well as the prolonged latency （P<0.05， P<0.01）. Furthermore， the contents and expression levels of IL-6， TNF-α， IL-1β， Bax， Aβ_1-42， Tau， and p-Tau （Ser404） were significantly increased， and the activity and expression of SOD， GSH-Px， ERα， PI3K， Akt， and Bcl-2 were significantly decreased （P<0.05， P<0.01）. Compared to those in model group， the rats in estradiol group and groups with different doses of PRP noticeably presented with amelioration of neuronal damage， along with increased activity time and shuttle frequency in the central zone， elevated new object recognition index and exploration frequency， shortened latency， prolonged activity time， and increased platform crossings in the target quadrant （P<0.05， P<0.01）. What is more， the contents and expression levels of IL-6， TNF-α， IL-1β， Bax， Aβ_1-42， Tau， and p-Tau （Ser404） were significantly reduced， whereas the activity and expression levels of SOD， GSH-Px， ERα， PI3K， Akt， and Bcl-2 were markedly elevated （P<0.05， P<0.01）. ConclusionPRP can improve the cognitive and emotional functions of AD model rats， and its mechanisms are probably related to modulating the ERα/PI3K/Akt pathway as well as inhibiting Aβ， Tau， neuro-inflammation， oxidative stress， and apoptosis， resulting in alleviation of neuronal damage.

ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

This article systematically reviews and examines the historical evolution of Bambusae Succus as a medicinal material， covering aspects such as nomenclature， origin， geographical distribution， harvesting and processing methods， quality assessment， therapeutic effects and indications， by consulting ancient herbal texts， medical compendia， and modern literature. The aim is to provide a reference for the development and utilization of famous classical formulas containing this herb. Research indicated that Bambusae Succus was first documented in the Shennong Bencaojing during the Han dynasty， with Zhuli being the standard name used throughout history， alongside aliases like Zhuzhi， Zhuyou and Huoquan. Historically， the primary source of Bambusae Succus has been Phyllostachys nigra var. henonis（Danzhu）， although other species such as Pleioblastus amarus and Bambusa emeiensis have also been used medicinally. Ancient records predominantly noted its origin in Yizhou（present-day Chengdu and surrounding areas in Sichuan） and the Wuling region（between present-day Hunan， Guangdong， Guangxi and Jiangxi provinces）， while contemporary sources are mainly from regions south of the Yangtze River and southwestern China. Traditionally， Bambusae Succus was harvested from bamboo that had grown for exactly one year， today， it can be collected year-round without strict age requirements. Ancient preparation methods included direct fire roasting or dry distillation， whereas modern industrial production employs dry distillation， reflux extraction， and percolation. In terms of quality evaluation， ancient texts considered a sweet taste to be superior， while today， clarity and transparency are prioritized. Historically， Bambusae Succus was characterized as sweet and cold nature， targeting the lung and stomach meridians， with uses evolving from clearing heat and resolving phlegm to nourishing Yin， moistening dryness， and relaxing tendons and unblocking meridians. Modern descriptions classify it as sweet， bitter， and cold in nature， affecting the heart， liver， and lung meridians， with functions including clearing heat， resolving phlegm， and facilitating orifices. It is indicated for conditions such as stroke with phlegm confusion， lung heat with phlegm congestion， convulsions， epilepsy， excessive phlegm in febrile diseases， high fever with thirst， irritability during pregnancy， and tetanus， with more clearly defined applications. Based on the results of the research， it is recommended that when developing and utilizing famous classical formulas containing Bambusae Succus， the one-year-old Phyllostachys nigra var. Henonis， which has been highly praised throughout history， should be selected as the source material. Industrial production should adopt the dry distillation method. Furthermore， in-depth research should be conducted on the modern technological characterization of the traditional quality control indicator of sweet taste， and reasonable modern quality control standards should be established.

ObjectiveTo observe the short-term and long-term efficacy of traditional Chinese medicine （TCM） surgical operations in treating mixed hemorrhoids. MethodsA multi-center retrospective cohort study was conducted， collecting clinical data from 17，831 mixed hemorrhoid surgery patients in 8 top-tier TCM hospitals in Jiangsu Province. Standardized and structured datasets were obtained through artificial intelligence models. Patients who underwent western surgical treatment were categorized into the western surgery group （11,646 cases）， and those receiving TCM surgical operations were categorized into the TCM surgery group （6185 cases）. Propensity score matching （1∶1 matching） was used to balance baseline data between groups. The primary outcome was the one-year recurrence rate， and secondary outcomes included the main symptoms （rectal bleeding， degree of prolapse） and secondary symptoms （anal distension， anal edema， wound secretion and exudation， anal stenosis， residual skin tags， perianal itching， and anal pain） measured on days 7， 28， and 60 after discharge. ResultsAfter matching， 2194 patients were included in each group. Symptom scores showed that at 28 days after discharge， the TCM surgical group had superior improvement in rectal bleeding ［OR=5.786， 95%CI （3.092，10.827）］， degree of prolapse ［OR=4.510， 95%CI （1.649，12.333）］， and anal edema ［OR=3.188， 95%CI （1.295，7.845）］ compared to the western surgical group. At 60 days post-discharge， the TCM group still showed advantages in improving rectal bleeding ［OR=5.237， 95%CI （1.077，25.464）］ and anal pain ［OR=11.697， 95%CI （1.186，115.336）］ （P＜0.05）. Long-term follow-up showed that the one-year recurrence rate in the TCM surgery group was 1.1% （8/726）， while that in the western surgery group was 2.3% （10/444）， with no statistically significant difference between the two groups （P＞0.05）. ConclusionBased on real-world data， TCM surgical treatment for mixed hemorrhoids shows significant short-term symptom improvement， particularly in terms of hemostasis， reducing swelling， and alleviating prolapse of anal masses.