By systematically combing ancient and modern literature， this paper examined Tribuli Fructus and Astragali Complanati Semen（ACS） used in the famous classical formulas from the aspects of name， origin， production area， harvesting and processing， clinical efficacy， so as to provide a basis for the development of famous classical formulas containing such medicinal materials. The results showed that the names of Tribuli Fructus in the past dynasties were mostly derived from its morphology， and there were nicknames such as Baijili， Cijili and Dujili. The name of ACS in the past dynasties were mostly originated from its production areas， and there were nicknames such as Baijili， Shayuan Jili and Tongjili. Because both of them had the name of Baijili， confusion began to appear in the Song dynasty. In ancient and modern times， the main origin of Tribuli Fructus were Tribulus terrestris， and ancient literature recorded the genuine producing areas of Tribuli Fructus was Dali in Shaanxi and Tianshui in Gansu， but today it is mainly cultivated in Anhui and Shandong. The fruit is the medicinal part， harvested in autumn throughout history. There is no description of the quality of Tribuli Fructus in ancient times， and the plump， firm texture， grayish-white color is the best in modern times. Traditional processing methods for Tribuli Fructus included stir-frying and wine processing， while modern commonly used is purified， fried and salt-processed. The ancient records of Tribuli Fructus were spicy， bitter， and warm in nature， with modern research adding that it is slightly toxic. The main effects of ancient and modern times include treating wind disorders， improving vision， promoting muscle growth， and treating vitiligo. The mainstream base of ACS used throughout history is Astragalus complanatus. Ancient texts indicated ACS primarily originated from Shaanxi province. Today， the finest varieties come from Tongguan and Dali in Shaanxi. The medicinal part is the seed， traditionally harvested in autumn. Modern harvesting occurs in late autumn or early winter， followed by sun-drying. Ancient texts valued seeds with a fragrant aroma as superior， while modern standards prioritize plump， uniform and free of impurities. Traditional processing methods for ACS included frying until blackened and wine-frying， while modern practice commonly employs purification methods. In terms of medicinal properties， the ancient and modern records are sweet and warm in nature. Due to originally classified under Tribuli Fructus， its effects were thus regarded as equivalent to those of Tribuli Fructus， serving as the medicine for treating wind disorders， additional functions included tonifying the kidneys and treating vitiligo. The present record of its efficacy is to tonify the kidney and promote Yang， solidify sperm and reduce urine， nourish the liver and brighten the eye， etc. Based on the textual research results， it is suggested that when developing the famous classical formulas of Tribuli Fructus medicinal materials， we should pay attention to the specific reference object of Baijili， T. terrestris and A. complanatus should be identified and selected， and the processing method should be in accordance with the requirements of the formulas.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

OBJECTIVE To observe the short-term efficacy and safety of venetoclax combined with homoharringtonine and cytarabine in the treatment of acute myeloid leukemia （AML）. METHODS The data of 40 newly diagnosed AML patients admitted to our hospital from October 2022 to November 2023 were retrospectively collected and divided into observation group and control group according to treatment plan， with 20 cases in each group. The patients in the control group were given Daunorubicin hydrochloride for injection+Cytarabine for injection， and the patients in the observation group were given Venetoclax tablets+ Homoharringtonine injection+Cytarabine for injection. The patients in both groups were given relevant medicine， with 28 days as one cycle. The short-term efficacy， negative rate of minimal residual disease （MRD）， duration of granulocyte deficiency， duration of platelet （PLT） ＜20×109 L－1， transfusion volume of suspended red blood cells and platelet， and the occurrence of adverse drug reactions were evaluated in both groups after 1 cycle of induction chemotherapy. RESULTS The complete remission or complete remission with incomplete hematologic recovery （CR/CRi） rate in the observation group was significantly higher than control group （P＜0.05）， and the negative rate of MRD in the observation group was also significantly higher than control group （P＜0.05）. However， in low-， medium- and high-risk patients， there was no statistical significance in CR/CRi rates between the two groups （P＞0.05）. There were no significant differences in the duration of agranulocytosis， the duration of PLT ＜20×109 L－1， the amount of suspended red blood cell transfusion， the amount of platelet transfusion， the incidence of hematologic toxicity and the incidence of non-hematologic toxicity between 2 groups （P＞0.05）. CONCLUSIONS Venetoclax combined with homoharringtonine and cytarabine show good short-term efficacy and safety in the treatment of AML.

Objective To investigate the value of multiparametric CT features for predicting the risk classification of gastric stro-mal tumor(GST).Methods The clinical data from 139 patients with GST were retrospectively collected.According to the patho-logical risk results,the patients were divided into two groups:a low-risk GST group(including very low-and low-risk)with 75 patients and a high-risk GST group(including medium and high-risk)with 64 patients.The CT features between low-risk GST group and high-risk GST group were compared using chi-squared test or t-test.The risk factors of high-risk GST were identified by univariate analysis.The prediction models were built by multivariate logistic regression.The performance of models were evaluated by receiver oper-ating characteristic(ROC)curve.Results There were significant differences in the maximum tumor diameter,minimum tumor diameter,arterial phase enhancement degree,venous phase enhancement rate,arterial phase enhancement degree rate,venous phase enhance-ment degree rate,cystic,and necrosis between low-risk GST group and high-risk GST group,which were associated with the risk classification of GST.The area under the curve(AUC)of the quantitative features-based model that combined maximum tumor diam-eter,minimum tumor diameter,arterial phase enhancement degree,venous phase enhancement rate,arterial phase enhancement degree rate and venous phase enhancement degree rate,showed a significantly higher performance than the qualitative features-based model that incorporated cystic and necrosis(0.981 vs 0.850,P<0.001).Conclusion Maximum tumor diameter,minimum tumor diameter,arterial phase enhancement degree,venous phase enhancement rate,arterial phase enhancement degree rate,venous phase enhance-ment degree rate,as well as cystic and necrosis,are associated with the risk classification of GST and can predict the high-risk GST.

Herein, we designed a dual-response shape transformation and charge reversal strategy with chemo-photodynamic therapy to improve the blood circulation time, tumor penetration and retention, which finally enhanced the anti-tumor effect. In the system, hydrophobic photosensitizer chlorin e6 (Ce6), hydrophilic chemotherapeutic drug berberrubine (BBR) and matrix metalloproteinase-2 (MMP-2) response peptide (PLGVRKLVFF) were coupled by linkers to form a linear triblock molecule BBR-PLGVRKLVFF-Ce6 (BPC), which can self-assemble into nanoparticles. Then, positively charged BPC and polyethylene glycol-histidine (PEG-His) were mixed to form PEG-His@BPC with negative surface charge and long blood circulation time. Due to the acidic tumor microenvironment, the PEG shell was detached from PEG-His@BPC attributing to protonation of the histidine, which achieved charge reversal, size reduction and enhanced tumor penetration. At the same time, enzyme cutting site was exposed, and the spherical nanoparticles could transform into nanofibers following the enzymolysis by MMP-2, while BBR was released to kill tumors by inducing apoptosis. Compared with original nanoparticles, the nanofibers with photosensitizer Ce6 retained within tumor site for a longer time. Collectively, we provided a good example to fully use the intrinsic properties of different drugs and linkers to construct tumor microenvironment-responsive charge reversal and shape transformable nanoparticles with synergistic antitumor effect.

Objective To evaluate the clinical value of maternal serum 25(OH)D level and bilateral uterine artery S/D mean in early prediction of pre-eclampsia(PE). Methods Sixty normal pregnancy women(normal group),40 mild preeclampsia women(MPE group)and 60 severe preeclampsia women(SPE group)who were examined in Changzhou First People′s Hospital and Changzhou Maternal and Child Health Care Hospital between January 2016 and June 2018 were included. The mean value of S/D of bilateral uterine artery was measured from 15th to 20th weeks in all the 3 groups,and serum 25(OH)D level of the mother was measured at 24th week. Meanwhile, the ROC curves of S/D mean value,serum 25(OH)D level and combined detection were drawn to compare the area under each curve(AUC),and the diagnostic efficiency of S/D mean value,serum 25(OH)D level and combined detection PE were also calculated. Results The incidence of adverse pregnancy outcome in SPE group was significantly higher than that in MPE group,and that in MPE group was significantly higher than that in normal group(P < 0.05). The mean value of S/D of bilateral uterine artery in SPE group was(4.09 ± 0.62),which was higher than that in MPE group(3.26 + 0.55)and in normal group(2.62 ± 0.51),while the mean value of S/D in MPE group was significantly higher than that in normal group and the difference was statistically significant(P < 0.05). The level of serum 25(OH)D in SPE group was(32.44 ± 5.84),which was significantly lower than that in MPE group(37.15 ± 5.90)and in normal group(42.57 ± 7.44),while the serum 25(OH)D level in MPE group was significantly lower than that in normal group,and the difference was statistically significant(P < 0.05). The mean value of S/D of bilateral uterine artery in the pre-eclampsia group was negatively correlated with 25(OH)D level(r = -0.66,P < 0.01). The area under the ROC curve separately detected by S/D mean value and 25(OH)D level was 0.787 and 0.719 respectively,both of which were lower than that by jointly detection(0.908)and the difference was statistically significant(P < 0.001). Conclusion Both the mean S/D value of bilateral uterine arteries and serum 25(OH)D level can be used for the diagnosis and monitoring of pre-eclampsia,and the diagnostic efficacy of the combined detection is superior to that of single detection.

AIM: JS-38 (mitothiolore), a synthetic version of a metabolite isolated from Xenorhabdus sp., was evaluated for its anti-tumor and white blood cell (WBC) elevating activities. METHOD: These anti-proliferative activities were assessed in vitro using a panel of ten cell lines. The anti-tumor activities were tested in vivo using B16 allograft mouse models and xenograft models of A549 human lung carcinoma and QGY human hepatoma in nude mice. The anti-tumor interactions of JS-38 and cyclophosphamide (CTX) or 5-fluorouracil (5-Fu) were studied in a S180 sarcoma model in ICR mice. Specific stimulatory effects were determined on peripheral neutrophils in normal and CTX- and 5-Fu-induced neutropenic mice. RESULTS: The IC50 values ranged from 0.1 to 2.0 μmol·L(-1). JS-38 (1 μmol·L(-1)) caused an increase in A549 tumor cell apoptosis. Multi-daily gavage of JS-38 (15, 30, and 60 mg·kg(-1)·d(-1)) inhibited in vivo tumor progression without a significant effect on body weight. JS-38 additively enhanced the in vivo anti-tumor effects of CTX or 5-Fu. JS-38 increased peripheral neutrophil counts and neutrophil rates in normal BALB/c mice almost as effectively as granulocyte colony-stimulating factor (G-CSF). In mice with neutropenia induced by CTX or 5-Fu, JS-38 rapidly restored neutrophil counts. CONCLUSION These results suggest that JS-38 has anti-tumor activity, and also has the ability to increase peripheral blood neutrophils.
Animals ; Antineoplastic Agents ; administration & dosage ; metabolism ; Cell Count ; Female ; Humans ; Hydrocarbons, Fluorinated ; administration & dosage ; metabolism ; Lung Neoplasms ; drug therapy ; physiopathology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred ICR ; Neutrophils ; cytology ; drug effects ; Xenorhabdus ; chemistry ; metabolism