OBJECTIVE To prepare an intelligent responsive liposome-hydrogel nanopreparation co-loaded with gambogic acid （GA）， and characterize its antitumor activity in vitro . METHODS GA-ICG-Lip-gel was prepared by ethanol injection and cold dissolution， incorporating GA and the photosensitizer indocyanine green （ICG）. The appearance and microscopic morphology of GA-ICG-Lip-gel were observed， its encapsulation efficiency and drug loading capacity were measured， and its photothermal conversion performance， photothermal stability， and infrared imaging properties were investigated， along with the determination of its in vitro release profile. Human breast cancer MCF-7 cells were used as objects to investigate the effects of GA-ICG-Lip-gel （or with near-infrared light irradiation） on cell viability， migration ability， and the cellular uptake capacity of GA-ICG-Lip-gel. RESULTS GA-ICG-Lip-gel existed in a solution state at room temperature and transformed into a gel state at 37 ℃. Its microstructure was dense with small pores， and its encapsulation efficiency and drug loading were （96.07±0.86） % and （6.28±1.16） %， respectively. After exposure to near-infrared light， the temperature of GA-ICG-Lip-gel rose above 42 ℃， with no significant attenuation observed in the heating curve. The heating efficiency was dependent on both the irradiation time and drug concentration. Compared to media without gelatinase， the cumulative release rate of GA-ICG-Lip-gel increased in media containing gelatinase. In vitro studies showed that GA-ICG-Lip-gel could be efficiently taken up by MCF-7 cells； GA-ICG-Lip-gel significantly inhibited the viability and migration ability of MCF-7 cells （ P ＜0.05）， and this inhibitory effect was further enhanced under near-infrared light irradiation. CONCLUSIONS This study successfully prepares GA-ICG-Lip-gel， which exhibits favorable photothermal conversion properties and temperature/enzyme dual-responsive drug release characteristics， and demonstrates significant inhibitory effects on the proliferation and migration of breast cancer cells.

Objective The kinetic parameters of Lin's squeezing-pressing adjustment manipulation were collected for the analysis of its mechanical characteristics,thus to establish a standardized operating procedure to guide clinical teaching of this technique.Methods Ten healthy male trainees(aged 20-30 years)from the Tuina Department of Guangdong Provincial of Chinese Medicine were selected as the subjects.A multi-point thin-film pressure testing system was used to collect mechanical parameters during the operation of Lin's squeezing-pressing adjustment manipulation.The mechanical characteristics were analyzed,and then a mathematical model of time-mechanics curve was constructed.Results(1)The kinetic parameters of Lin's squeezing-pressing adjustment manipulation were as follows:preload force averaged(279.45±19.36)N with a duration of(0.98±0.03)s,the valley value of preload force averaged(137.45±3.59)N,the maximum impact force was(495.56±7.33)N,the impact duration averaged(0.15±0.01)s,the impact velocity averaged(3 183.96±94.76)N/s,and the impulse was(57.16±1.82)N/s.(2)The fitting function of impact force showed large absolute values for both ascending and descending slopes,and the ascending slope was significantly greater than the descending slope,indicating that the Lin's manipulation stressed on rapid outburst of the strength and withdrawal of the strength.(3)One-way ANOVA revealed no statistically significant differences in the preload force and its duration and valley value,the maximum impact force,and impact time among different operators(P＞0.05).Conclusion The analysis of kinetic parameters demonstrates that skilled operators maintain relatively stable mechanical parameters when performing Lin's squeezing-pressing adjustment manipulation.This study provides a preliminary digital analysis of the mechanical characteristics of Lin's bone-setting manipulation in addressing"bone misalignment and tendon displacement",which supplies objective evaluation criteria for the technique.

ObjectiveTo investigate the analgesic effect of Tuina at the "Weizhong （BL 40）" on neuropathic pain in a rat model of chronic constriction injury （CCI） of the sciatic nerve and its potential central spinal mechanisms. MethodsThirty-two Sprague-Dawley rats were randomly divided into four groups （8 rats in each group）， sham-operated group， model group， Tuina group， and blockade group. The CCI model was established in the model group， Tuina group， and the blockade group by ligating the sciatic nerve with catgut， while the sham-operated group underwent only sciatic nerve exposure without ligation. From postoperative day 4 to day 14， rats in the Tuina group and the blockade group received Tuina manipulation at the "Weizhong （BL 40）" using a dynamic pressure distribution measurement system （5 N pressure， 2 Hz frequency， 10 min per session， once daily）. The blockade group also received intraperitoneal injections of the microglial inhibitor minocycline （10 mg/kg） once daily. The sham-operated and the model group underwent the same handling and fixation as the Tuina group without actual Tuina. Mechanical withdrawal threshold （MWT） and paw withdrawal latency （PWL） were measured before surgery and on day 3， 7， 10， and 14 post-surgery. Transmission electron microscopy was used to evaluate sciatic nerve injury and repair， measuring axon diameter and total myelinated fiber diameter to calculate the g-ratio. Western Blotting was performed to detect the protein levels of ionized calcium-binding adapter molecule 1 （Iba-1）， CD206， CD68， interleukin-10 （IL-10）， and β-endorphin （β-EP） precursor pro-opiomelanocortin （POMC） in the ipsilateral spinal dorsal horn. ResultsCompared with the sham-operated group， the model group showed significantly reduced MWT and PWL on day 3， 7， 10， and 14 （P＜0.01）. Compared with the model group， the Tuina group and the blockade group showed increased MWT and PWL on day 10 and 14 （P＜0.05）. Compared with the Tuina group， the blockade group exhibited higher MWT on day 7， 10， and 14， and higher PWL on day 10 （P＜0.05）. Sciatic nerve pathological morphology revealed intact and well-structured myelin in the sham-operated group， while the model group exhibited myelin collapse， distortion， and myelin ovoid formation. The Tuina group displayed partially irregular myelin with occasional myelin collapse， whereas the blockade group exhibited partial myelin irregularities and phospholipid shedding. Compared with the sham-operated group， the model group showed a decreased g-ratio and increased levels of Iba-1 and CD68 in the spinal dorsal horn （P＜0.05 or P＜0.01）. Compared with the model group， the Tuina group and the blockade group exhibited an increased g-ratio and reduced Iba-1 and CD68 levels. Additionally， the Tuina group showed elevated levels of CD206， IL-10， and POMC， whereas the blockade group had decreased CD206 levels （P＜0.05）. ConclusionTuina at "Weizhong （BL 40）" alleviates neuropathic pain in CCI rats， potentially by regulating microglial activation in the spinal cord， inhibiting M1 polarization while promoting M2 polarization， and activating the IL-10/β-EP pathway to exert analgesic effects.

Objective To analyze the levels of serum CTCs and ctDNA in NSCLC patients receiving first-line EGFR-TKI treatment, and to explore the clinical value of CTCs and ctDNA detection in assessing the efficacy of treatment for advanced lung cancer. Methods A total of 109 NSCLC patients receiving first-line EGFR-TKI treatment were enrolled. Serum tumor markers CEA, CTCs, and ctDNA were detected at baseline and after one month of treatment. Chest CT scans were performed, and treatment efficacy was evaluated based on RECIST1.1 criteria. CTCs were counted by enrichment-staining-computational algorithm to analyze malignant features, while ctDNA was assessed using digital PCR. Results Survival rate was low in patients with abnormal CEA and ctDNA tests at baseline and in patients with reduced serum CTCs after treatment. In the SD subgroup of patients with brain metastases and advanced stage, the PFS benefit was low. Conclusion Patients in the SD subgroup have significantly higher recurrence risks than those in the PR or CR subgroups. Therefore, CTC and ctDNA testing should be applied to patients in the SD subgroup to identify high-risk patients with poor response to EGFR-TKI treatment, intervene with additional treatment promptly, and obtain long progression-free survival.

Objective:To explore the feasibility and clinical effect of surgical treatment for patients with malignant tumor complicated with coronary heart disease.Methods:The medical records of 12 patients with malignant solid tumor complicated with coronary heart disease who were treated by the same surgical team in the Department of Cardiac Surgery, the First Hospital of Tsinghua University from January 2018 to May 2025 were collected retrospectively, including 8 cases of digestive system tumors, 3 cases of lung tumors and 1 case of urinary system tumor. All patients underwent simultaneous (4 cases) or staged (8 cases) coronary artery bypass grafting and tumor resection. Coronary artery bypass grafting under cardiopulmonary bypass was performed in 2 cases, and off-pump coronary artery bypass grafting was performed in the remaining 10 cases. Postoperative follow-up was conducted.Results:None of the 12 patients died during hospitalization, and all were cured and discharged. No perioperative myocardial ischemia or infarction occurred during hospitalization, and no postoperative surgical bleeding occurred. The 12 patients were followed up for 1 month to 7 years and 5 months. One patient with rectal cancer complicated with coronary heart disease had liver and lung metastases 13 months after surgery and died suddenly during the second cycle of chemotherapy 16 months after surgery. The remaining 11 patients survived.Conclusions:It is feasible to perform coronary artery bypass grafting and tumor resection in patients with coronary heart disease complicated with malignant tumor, and the short-term and medium-term effects are satisfactory.

Objective:To investigate the expression of heat shock factor binding protein 1 (HSPB1) in endometrial carcinoma and its clinical significance.Methods:The pan-cancer dataset after standardization and unification was downloaded from the University of California Santa Cruz (UCSC) Genome database (updated to December 6, 2019), and the expression of HSPB1 in pan-cancer was analyzed. The transcriptome data of endometrial carcinoma of the uterus from the Cancer Genome Atlas (TCGA) database were downloaded (updated to July 21, 2016), including 552 cases of endometrial carcinoma and 35 cases of corresponding adjacent tissue samples. The clinical data of 543 patients with endometrial cancer were obtained. The differences in the expression levels of HSPB1 in patients with different clinicopathological features were compared. R 4.3.1 software maxstat was used to calculate the optimal critical value (>46.30) of HSPB1 expression, and the patients were divided into HSPB1 low expression group (<46.30) and HSPB1 high expression group (≥46.30). Kaplan-Meier method was used to analyze the difference in prognosis between the 2 groups, and log-rank test was performed. The top 50 genes with positive and negative correlation with HSPB1 were screened by LinkedOmics database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on HSPB1. The interaction network of HSPB1 protein was analyzed by STRING database and Cytoscape 3.9.1 software. The correlation between HSPB1 expression and various immune cell infiltration levels was analyzed by using the TIMER2.0 database.Results:The expression of HSPB1 in 27 kinds of tumor tissues was higher than that in paracancerous tissues, and the expression of HSPB1 in 2 kinds of tumor tissues was lower than that in paracancerous tissues (all P < 0.05). In the transcriptome data of 552 cases of endometrial cancer and 35 cases of corresponding paracancerous tissues in the TCGA database, the relative expression level of HSPB1 in endometrial cancer tissues was higher than that in corresponding paracancerous tissues ( t = -2.90, P = 0.005). The result of the comparison of relative expression level of HSPB1 in endometrial cancer patients with different clinicopathological features showed that patients aged < 65 years had higher expression level compared to those aged ≥ 65 years, patients at clinical stage Ⅰ-Ⅱ had higher expression level compared to those at stage Ⅲ-Ⅳ, patients with Grade grading G 1-G 2 had higher expression level compared to those with G 3, and patients with pathological type I had higher expression level compared to those with type Ⅱ (all P < 0.05). Of the 543 patients, 2 were lost to follow-up, and the overall survival of the remaining 541 patients with high HSPB1 expression was better than that of those with the low expression ( HR = 0.532, 95% CI: 0.333-0.849, P = 0.008). HSPB1 and its related genes were mainly involved in estrogen signaling, p53 signaling and other pathways; HSPB1 was involved in cysteine-type endopeptidase inhibitor activity and calcium-dependent protein binding. The top 10 genes with the strongest correlation with HSPB1 in protein-protein interaction analysis were DSG3, EVPL, PKP1, DSC3, PKP3, PPL, KRT5, IVL, TGM1 and CSTA. The expression of HSPB1 was negatively correlated with tumor purity ( r = -0.025, P < 0.01), and positively correlated with CD4 + T cells ( r = 0.204, P < 0.01), CD8 + T cells ( r = 0.225, P < 0.01), B cells ( r = 0.285, P < 0.01), NK cells ( r = 0.269, P < 0.01), macrophages ( r = 0.234, P < 0.01) and dendritic cells ( r = 0.354, P < 0.01). Conclusions:The high expression of HSPB1 is associated with clinicopathological features, prognosis and immune infiltration in patients with endometrial carcinoma. It may be one of the reference indexes for predicting the prognosis of patients with endometrial cancer.

Objective To establish the HPLC analysis method for ketoconazole related substances,and to provide technical support for the improvement of the quality standard and the purity of ketoconazole.Methods Gradient elution conditions were optimized based on the chromatographic parameters outlined in the 2024"British Pharmacopoeia"for ketoconazole cream.A C18 column(4.6 mm×150 mm,3 μm)was used to facilitate the elution process using a gradient of acetonitrile and acetate buffer,and detection performed at a wavelength of 230 nm.Results The known impurities and potentially genotoxic impurities in the material drugs of ketoconazole can be more effectively separated using the established methods,which are both robust and highly sensitive.The content of the two potentially geno toxic impurities,six known impurities and unknown impurities in the 21 batches of ketoconazole sourced from five raw material pharmaceutical companies is below the specified limit requirements.Conclusion This method contributes to improving the quality of ketoconazole ingredients,ensuring the safety of ketoconazole preparations,and better supporting the regulatory supervision.

Objective:To investigate the clinical efficacy of posterior midline incision combined with anteromedial approach in the treatment of complex olecranon fracture-dislocation.Methods:A retrospective analysis was performed on 26 patients (15 males and 11 females) with olecranon fracture-dislocation who were admitted from January 2020 to January 2024, including 5 cases of anterior transolecranon fracture-dislocation (2 cases of upper ulnar-radial joint dislocation), 21 cases of posterior transolecranon fracture-dislocation (5 cases of them were accompanied by upper ulnar-radial joint dislocation). Among them, there were 13 cases of traffic accidents, 7 cases of falling from heights, and 6 cases of walking falls. The average age is 45.1±15.3 years old (21-84 years old).Results:The operation time was 151.2±41.9 minutes, average tourniquet time was 93.7±22.6 minutes, and the intraoperative blood loss was 76.2±20.2 ml. The average follow-up was 16(12, 23) months, and the VAS score decreased significantly and the MEPS score increased significantly over time. At the last follow-up, the VAS score was 2(1, 2), and the MEPS score was 86.5±10.3, with 16 cases excellent, 7 cases good, and 3 cases medium, with an excellent rate of 89%. The range of motion of flexion-extension and pronation-supination were 119.3°±13.5°and 138.6°±15.2° respectively. Complications included 16 cases of ectopic ossification, of which 4 patients with significant effects on elbow function underwent surgical release 3-6 months after surgery. 1 case of ulnar nerve injury symptoms improved after emergency ulnar nerve release, and 1 case of elbow subluxation due to inaccurate coronoid process reduction and fixation. There were no serious complications such as vascular injury, internal fixation failure, fracture nonunion, and incision infection.Conclusion:The posterior midline incision combined with anteromedial approach can effectively treat complex olecranon fracture-dislocation and meet the requirements of early postoperative elbow rehabilitation.

The clustered regularly interspaced short palindromic repeat-CRISPR-associated protein (CRISPR-Cas) system is renowned for its exceptional gene-editing capabilities. In recent years, the discovery of the trans-cleavage activity of Cas12 and Cas13 proteins has shown great potential in the field of molecular diagnostics. The trans-cleavage activity of the CRISPR-Cas system has been widely applied in point-of-care testing (POCT). This article will provide a detailed discussion on the principles, advantages, and challenges of combining the CRISPR-Cas system with lateral flow assays, colorimetric methods, microfluidic technologies, smartphone applications, and portable detection sets. The CRISPR-Cas system demonstrates versatility in the POCT field with its ability to detect nucleic acids, pathogenic microorganisms, and non-nucleic acid targets. As CRISPR-Cas-based POCT continues to advance, these developments provide strong support for the formulation of personalized medical and public health strategies, further promoting the realization of precision medicine.

Hepatitis virus is the main pathogen causing liver inflammation and damage. Early detection is crucial for the effective treatment of hepatitis. The detection technology of hepatitis virus has gone through multiple stages, including immunological detection technology and nucleic acid detection technology. The emergence of emerging molecular detection technologies makes its detection more sensitive and convenient, including nanotechnology, Raman spectroscopy technology, microfluidic technology and biosensor technology. The development of these technologies has promoted the early diagnosis of hepatitis, but their clinic applications are still facing challenges. In the future, the development of hepatitis virus detection technology is expected to transform in the form of multidimensional and interdisciplinary innovation process, with its core objectives being the realization of more precise, convenient, and accessible detection methods, thereby comprehensively advancing the progress of hepatitis prevention and control efforts.