Codonopsis Radix is a Codonopsis plant belonging to Campanulaceae family.It is widely used as a Chinese medicinal for invigorating qi in Chinese medicine clinics.The chemical compositions of Codonopsis Radix mainly contain flavonoids,alkaloids,sugars,saponins,steroids,amino acids,etc..It mainly exhibits the pharmacological effects such as enhancing the immune system function,improving gastrointestinal function,anti-inflammation,anti-tumor,improving the ability of learning and memory,regulating the cardio-cerebral vascular system,and slowing down the aging process,and so on.Based on a large number of literature studies on Codonopsis Radix at home and abroad in recent years,this paper summarizes its pharmacological effects.The aim of the review is to provide a certain theoretical basis and rationale for the research and application of Codonopsis Radix.

Objective To explore the medication law of Professor Wang Qingguo for the treatment of insomnia based on data mining technology.Methods Paper-based prescriptions for Professor Wang Qingguo's treatment of insomnia from December 2016 to August 2023 were collected and a database was constructed.The screened prescriptions were subjected to data mining such as frequency statistics,association rule analysis,and clustering analysis.Results Totally 399 effective outpatient prescriptions were screened-out,involving 276 kinds of Chinese materia medica,with a total frequency of 6738 times.There were 38 Chinese materia medica with a frequency of use≥50.The properties were mainly warm,cold and mild,the tastes were mainly sweet,bitter and pungent,and mainly belong to the lung,spleen and heart meridians.Association rule analysis showed that the most commonly used drug combinations were"Fructus Tritici Levis-Scutellariae Radix-Bupleuri Radix","Pericarpium Citri Reticulatae-Scutellariae Radix-Pinelliae Rhizoma",etc.Association rule network analysis obtained a core prescription containing 12 kinds of Chinese materia medica for insomnia.Four new drug combinations were obtained by clustering analysis.Conclusion Professor Wang's treatment of insomnia has the characteristics of following the original meaning of Huang Di Nei Jing and Nan Jing,making good use of the classical prescription,applying combined prescription,flexible use of prescription,combining ancient and modern prescriptions,using specific medicine.It deeply reflects the academic view of"Tongping Zhihe".

Objective:To prepare a 177Lu labeled human epidermal growth factor receptor 2 (HER2) affibody 177Lu-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-maleimide (Mal)-cysteine (Cys)-ZHER 2: 342 ( 177Lu-NOTA-MZHER2 for short), and investigate its labeling process and anti-tumor properties. Methods:Two kinds of buffer systems (sodium acetate buffer system and sodium ascorbate buffer system) were investigated. The effects of pH value, precursor mass and reaction temperature on 177Lu labeling NOTA-MZHER2 were compared to obtain optimal labeling conditions. The radiochemical purity of labeled product was determined by instant thin-layer chromatography (ITLC), and its stabilities in PBS and plasma were observed. Human ovarian cancer cell line SKOV-3 was selected for cell internalization and cytotoxicity test to evaluate cell uptake and killing effect of 177Lu-NOTA-MZHER2. SKOV-3 tumor-bearing mice( n=3) were injected with 177Lu-NOTA-MZHER2, and microSPECT/CT imaging was performed. Another 40 tumor-bearing mice were divided into 22.2 MBq group (tail vein injection with probe of 22.2 MBq), control group (tail vein injection with PBS), low-dose group (tumor injection with probe of 3.7 MBq) and high-dose group (tumor injection with probe of 7.4 MBq). Tumor volume and mass of tumor-bearing mice were monitored after injection, and the anti-tumor effect and toxicity of probe were evaluated. Repeated measurement analysis of variance (Bonferroni method) was used to analyze the data. Results:The optimal labeling condition was 70-80 ℃ for 30 min in the system of sodium acetate buffer solution with pH=4 and precursor mass of 50 μg. Under these conditions, the labeling rate of 177Lu-NOTA-MZHER2 was (99.3±0.4)% and radiochemical purity was >99%. After 12 d in PBS and plasma, the radiochemical purities were (95.0±1.5)% and (95.0±2.1)%. Results of cell experiment showed that the internalization of 177Lu-NOTA-MZHER2 accounted for (29.02±3.50)% of the total uptake, and the survival rate of SKOV-3 cells was (48±6)% with the probe concerntration of 6×10 -3 Bq/L. SPECT imaging showed that 177Lu-NOTA-MZHER2 was still concentrated at the tumor site 96 h after injection with a dose of 18.5 MBq. Relative tumor volume (RTV) of tumor-bearing mice in 22.2 MBq group, high-dose group and low-dose group was significantly different from that in control group ( F=21.75, P<0.001). Twenty days after injection, RTV and relative body mass of the tumor-bearing mice in high-dose group were (140±7)% and (80±9)%, respectively. Compared with control group, high-dose group had obvious anti-tumor effect (both P<0.001). Conclusion:177Lu-NOTA-MZHER2 is successfully prepared, which is simple and efficient, and the probe has good anti-tumor effect.

Objective:To radiolabel hyperbranched polymer (HG)-modified liquid metal nanodroplet (LMND)@HG with 177Lu, and explore the radiotherapy sensitization effect on anti-breast cancer therapy. Methods:The ultrasonication method was used to prepare LMND@HG, and then 177LuCl 3 was mixed with LMND@HG to label 177Lu by alloying reactions. The labeling rate, plasma stability and cytotoxicity of 177Lu-LMND@HG were detected. Xenograft mouse model of breast cancer was constructed, and the tumor inhibition test was performed by an intratumoral injection. The tumor progression was monitored by in vivo imaging system. The mechanism of tumor inhibition was verified by immunohistochemistry and immunofluorescence assays. One-way analysis of variance, repeated measures analysis of variance, and the least significant difference t test were used to analyze the data. Results:177Lu was successfully labeled to LMND@HG with a high labeling efficiency >95%. The product did not require further purification and the plasma radiochemical purity was still higher than 95% after 5 d. The cytotoxicity test showed that a dose of 888 kBq (40 mg/L) 177Lu-LMND@HG had obvious toxicity to 4T1 cells, which was significantly lower than 177LuCl 3 (cell viabilities: (16.48±7.81)% vs (85.77±8.87)%; F=77.81, t=11.73, P<0.001) and LMND@HG ((46.53±5.75)%; t=6.20, P<0.001). The biological distribution results showed that 177Lu-LMND@HG was mainly distributed in tumor tissue 5 d after intratumoral injection. The results of the tumor inhibition experiment showed that 1.48 MBq 177Lu-LMND@HG could significantly inhibit the tumor growth compared with the 177LuCl 3 (tumor volume: (222.66±97.70) vs (789.13±245.04) mm 3;F=18.55, t=4.29, P=0.005). In vivo optical imaging of small animals showed that 1.48 MBq and 3.70 MBq 177Lu-LMND@HG both significantly inhibited the tumor growth. Immunofluorescence and immunohistochemical results showed that 177Lu-LMND@HG caused double-stranded DNA break, and suppressed the tumor growth by inhibiting cell proliferation and angiogenesis. Conclusions:A novel 177Lu-liquid metal-based reactive oxygen species (ROS) radiation sensitizer is successfully prepared in this study. The preparation method is efficient and convenient, and the product has high stability. 177Lu-LMND@HG shows an obvious radiotherapy sensitization effect on breast tumor-bearing mice.

Objective:To explore the value of baseline PET/CT parameters for predicting prognosis in patients with double-expression lymphoma (DEL).Methods:The clinical and 18F-FDG PET/CT data of 118 patients (66 males, 52 females; age: 28-85 years) with diffuse large B-cell lymphoma (DLBCL) diagnosed in Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University and the First Affiliated Hospital of Nanjing Medical University from June 2015 to September 2022 were retrospectively analyzed. The optimal thresholds for SUV max, total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) in predicting overall survival (OS) rate were determined using ROC curve analysis. Univariate and multivariate analyses, along with Kaplan-Meier survival analysis were performed to construct a survival prediction model. The effect of the model was evaluated by the calibration curve for the model, the time-dependent ROC curve analysis and decision curve analysis. Results:As of the last follow-up, 25 patients died, and the OS rate was 78.8%(93/118). The AUC of the ROC curve for TMTV was 0.705, with a corresponding optimal threshold of 230.9 cm 3. In multivariate analysis, Eastern Cooperative Oncology Group performance status (ECOG PS) score (hazard ratio ( HR)=3.886, 95% CI: 1.455-10.375; P=0.007) and TMTV ( HR=4.649, 95% CI: 1.665-12.979; P=0.003) were identified as independent predictors of OS. The combined model of ECOG PS score and TMTV was superior to ECOG PS score model and TMTV model alone in predicting OS. Conclusion:TMTV, a metabolic indicator, and ECOG PS score, a clinical risk factor, are independent predictors of OS in patients with DEL, and their combination can provide more accurate prognostic predictions.

Objective:To prepare a novel 68Ga-labeled bicyclic peptide targeting poliovirus receptor related protein 4 (PVRL4, Nectin-4), and evaluate its feasibility for breast cancer imaging via in vitro and in vivo experiments. Methods:A Biotin-modified bicyclic peptide targeting Nectin-4, Biotin-BMIC, was synthesized, and its targeting properties were preliminarily evaluated by in vitro cell staining experiments. BMIC was modified by 1, 4, 7-triazonane-1, 4-diacetic acid (NODA) and the labeling precursor NODA-BMIC was prepared. A potential PET probe targeting Nectin-4, 68Ga-NODA-BMIC was prepared by one-step labeling strategy. The imaging properties of the probe were investigated by in vivo microPET imaging and in vitro experiments in mice bearing breast tumors. Data were analyzed by independent-sample t test and repeated measures analysis of variance. Results:Fluorescence staining of the cells showed that the fluorescently labeled bicyclic peptide, Biotin-BMIC, was highly aggregated in Nectin-4 positive BT474 breast cancer cells compared to those in Nectin-4 negative MDA-MB-231 cells. The uncorrected yield of 68Ga-NODA-BMIC was (71.5±2.2)% and the radiochemical purity was greater than 95%. The specific activity was greater than 3 GBq/μmol. After incubation 10, 30, 60 and 120 min, higher radioactivity uptakes were found in BT474 breast cancer cells compared to those in MDA-MB-231 breast cancer cells respectively ( F=1 302.00, P<0.001). MicroPET imaging showed that the BT474 xenograft tumors were clearly visible with favorable contrast. A significant statistical difference in uptakes between BT474 and MDA-MB-231 xenograft tumor uptake at 10, 30, 60, and 120 min after probe injection respectively was existed ( F=1 826.00, P<0.001). At 60 min postinjection, the uptake value of BT474 tumors was (5.03±0.14) percentage activity of injection dose per gram of tissue (%ID/g), which was significantly higher than that of MDA-MB-231 tumors ((0.19±0.04) %ID/g; t=79.40, P<0.001). Meanwhile, the tumor-to-muscle ratios in the former were also greater than those in the latter ( F=222.00, P<0.001). At 60 min postinjection, the tumor-to-muscle ratio in the former was significantly higher than that in the latter (24.75±3.10 vs 1.30±0.15; t=14.31, P=0.002). The results were consistent with the immunohistochemistry staining. Conclusions:A novel bicyclic peptide PET probe targeting Nectin-4, 68Ga-NODA-BMIC, is easy to be synthesized and owns satisfactory labeling yield and radiological purity. The imaging performance is good and the target tissues could be visualized. It may play a unique role in the diagnosis and treatment of breast cancer.

Objective:To investigate the relationship between non-alcoholic fatty liver disease(NAFLD) and hepatic fibrosis and skeletal muscle mass in patients with type 2 diabetes mellitus(T2DM).Methods:A total of 685 T2DM patients diagnosed at the Endocrinology department of Lanzhou University First Hospital, from April 2022 to May 2023, were divided into NAFLD and Non-NAFLD groups, and the NAFLD group was further categorized into fibrosis and non-fibrosis based on aspartate aminotransferase(AST) /alanine aminotransferase(ALT) level. The differences in appendicular skeletal muscle mass(ASM), appendicular skeletal muscle mass index(ASMI), and the prevalence of muscle mass loss were compared across groups. The correlations between ASMI and NAFLD, as well as liver fibrosis were analyzed by binary logistic regression.Results:Among male T2DM patients, those with NAFLD had lower ASMI levels and a higher prevalence of muscle mass reduction compared to non-NAFLD group. Among female T2DM patients, those with NAFLD had lower levels of ASM and ASMI, and a higher prevalence of muscle mass reduction compared to non-NAFLD group. ASMI levels in both male and female T2DM patients were independently negatively correlated with NAFLD risk( OR=-0.696, 95% CI 0.579-0.837; OR=-0.757, 95% CI 0.629-0.911). In NAFLD patients, ASM and ASMI levels were lower in those with liver fibrosis compared to those without fibrosis; however, the prevalence of muscle mass reduction did not differ significantly. Among male NAFLD patients, ASMI levels were independently negatively correlated with the risk of liver fibrosis( OR=-0.726, 95% CI 0.537-0.983), while no correlation was found in female patients. Conclusion:Reduced muscle mass is independently associated with the risk of NAFLD in both male and female T2DM patients. In males, reduced muscle mass is also independently related to the risk of liver fibrosis.

Objective:To investigate the therapeutic effect of high-flow nasal cannula oxygen therapy (HFNC) and non-invasive positive pressure ventilation (NPPV) on patients with pulmonary edema caused by seawater drowning.Methods:A retrospective analysis method was used. Based on the Utstein database of emergency drowning in the First Hospital of Qinhuangdao, the clinical data of patients with seawater drowning pulmonary edema admitted to the emergency medicine department of the First Hospital of Qinhuangdao from January 1, 2019 to December 31, 2022 were collected. The patients were divided into NPPV group and HFNC group according to different ventilation methods. The general data, endotracheal intubation rate in 7 days, arterial blood gas analysis indexes [arterial partial pressure of oxygen (PaO 2), arterial partial pressure of carbon dioxide (PaCO 2), arterial oxygen saturation (SaO 2)] and hemodynamic indexes (systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, blood lactic acid) before and after treatment, length of stay in intensive care unit (ICU), oxygen therapy comfort of the two groups were compared. Results:A total of 54 patients were enrolled, including 21 patients in the NPPV group and 33 patients in the HFNC group. There were no significant differences in gender, age, state of consciousness and other general information between the two groups. Compared with NPPV group, the rate of endotracheal intubation in HFNC group within 7 days was significantly lower [24.2% (8/33) vs. 33.3% (7/21), P < 0.05]. Before treatment, there were no significant differences in arterial blood gas analysis and hemodynamics between the two groups. After treatment, the above indexes in both groups were significantly improved compared with those before treatment, and PaO 2, SaO 2, systolic blood pressure, diastolic blood pressure and mean arterial pressure in HFNC group were significantly higher than those in NPPV group [PaO 2 (mmHg, 1 mmHg≈0.133kPa): 93.56±6.37 vs. 82.14±6.25, SaO 2: 1.02±0.09 vs. 0.95±0.11, systolic blood pressure (mmHg): 117.37±8.43 vs. 110.42±8.38, diastolic blood pressure (mmHg): 79.43±7.61 vs. 72.21±4.32, mean arterial pressure (mmHg): 92.34±6.32 vs. 85.12±5.38], PaCO 2, heart rate and blood lactic acid were significantly lower than those in NPPV group [PaCO 2 (mmHg) : 34.26±5.63 vs. 37.24±6.22, heart rate (times/min): 73.38±7.56 vs. 86.25±5.41, blood lactic acid (mmol/L): 1.38±0.36 vs. 2.25±1.14], and the differences were statistically significant (all P < 0.05). In addition, the length of ICU stay in HFNC group was significantly shorter than that in NPPV group (days: 13.30±2.38 vs. 16.27±4.26), and the comfort rate of oxygen therapy was significantly higher than that in NPPV group [66.7% (22/33) vs. 42.8% (9/21)], with statistical significance (all P < 0.05). Conclusion:HFNC can improve the oxygenation of patients with pulmonary edema caused by seawater drowning, improve hemodynamics, reduce the rate of tracheal intubation, shorten the length of ICU stay, and improve the comfort of oxygen therapy, which has certain clinical application value.

ObjectiveTo investigate the ameliorative effect and mechanism of total saponins of Codonopsis Radix （TSC） on learning and memory impairment induced by D-galactose in aging mice. MethodTwenty-four male C57BL/6J mice were randomly assigned into four groups （n=6）： normal group， model group （200 mg·kg^-1 D-galactose）， TSC group （200 mg·kg^-1）， and donepezil group （3 mg·kg^-1）. After one week of pre-treatment， the mice in the model， TSC， and donepezil groups were administrated with corresponding agents for 8 weeks. In the ninth week， the Morris water maze test was performed to assess the learning and memory abilities. Histopathological changes in the brain were evaluated by hematoxylin-eosin （HE） and Nissl staining. Immunohistochemistry was used to detect the expression of nuclear factor kappa-B （NF-κB）， tumor necrosis factor-α （TNF-α）， and brain-derived neurotrophic factor （BDNF） in the brain tissue. The serum levels of glutathione peroxidase （GSH-Px）， catalase （CAT）， superoxide dismutase （SOD）， malondialdehyde （MDA）， TNF-α， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） were measured by enzyme-linked immunosorbent assay， on the basis of which the effects of TSC on neuroinflammation and memory impairment in D-galactose-induced aging mice were assessed. ResultCompared with the normal group， the model group exhibited decreased cognitive function， decreased activities of CAT， SOD， and GSH-Px in the serum （P<0.01）， and upregulated levels of MDA， TNF-α， IL-1β， and IL-18 （P<0.01）. In addition， partial neuronal damage and degeneration were observed in the hippocampus and cortex of the model group， accompanied by downregulated BDNF expression （P<0.05） and upregulated NF-κB and TNF-α expression （P<0.05）. Compared with the model group， TSC alleviated D-galactose-induced cognitive dysfunction， enhanced the activities of CAT， SOD， and GSH-Px （P<0.01）， lowered MDA， TNF-α， IL-1β， and IL-18 levels （P<0.01）， and ameliorated the pathological changes in the hippocampus and cerebral cortex. Additionally， TSC upregulated BDNF expression （P<0.05， P<0.01） and downregulated NF-κB and TNF-α expression （P<0.05， P<0.01） in the hippocampus and cerebral cortex. ConclusionTSC exerts a protective effect on cognitive dysfunction induced by D-galactose in aging mice by inhibiting oxidative stress and inflammation.

Chronic myeloid leukemia (CML) with e6a2 transcript type is very rare in clinic,which is usually related to disease aggressiveness. Its clinical characteristics and relationship with tyrosine kinase inhibitor efficacy are still unclear. In this paper, the clinical characteristics and related laboratory tests of a patient with e6a2 fusion gene positive CML characterized by multiple osteolytic bone destruction throughout the body and eosinophil infiltration in gastrointestinal tract, lymph nodes and other organs were retrospectively analyzed, and the relevant literature was reviewed. The patient was Ph chromosome positive with chromosome +8, and the common BCR::ABL1 transcript of CML was negative, but e6a2 transcript was positive detected by RT-PCR. The patient was treated with dasatinib 100 mg/d. Three months later, the patients achieved CHR, CCyR and MR4.0. However, the e6a2 transcript is very rare in clinical practice, and more cases of e6a2 transcript need to be studied to clarify its clinical characteristics and improve the treatment effect of these rare cases.