Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.

Osteoarthritis is a prevalent global joint disease, which is characterized by inflammatory reaction and cartilage degradation. Cyasterone, a sterone derived from the roots of Cyathula officinalis Kuan, exerts protective effect against several inflammation-related diseases. However, its effect on osteoarthritis remains unclear. The current study was designed to investigate the potential anti-osteoarthritis activity of cyasterone. Primary chondrocytes isolated from rats induced by interleukin (IL)-1β and a rat model stimulated by monosodium iodoacetate (MIA) were used for in vitro and in vivo experiments, respectively. The results of in vitro experiments showed that cyasterone apparently counteracted chondrocyte apoptosis, increased the expression of collagen II and aggrecan, and restrained the production of the inflammatory factors inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), metalloproteinase-3 (MMP-3), and metalloproteinase-13 (MMP-13) induced by IL-1β in chondrocytes. Furthermore, cyasterone ameliorated the inflammation and degenerative progression of osteoarthritis potentially by regulating the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. For in vivo experiments, cyasterone significantly alleviated the inflammatory response and cartilage destruction of rats induced by monosodium iodoacetate, where dexamethasone was used as the positive control. Overall, this study laid a theoretical foundation for developing cyasterone as an effective agent for the alleviation of osteoarthritis.
Animals ; Rats ; Chondrocytes ; NF-kappa B ; Iodoacetic Acid ; Inflammation ; MAP Kinase Signaling System ; Apoptosis

Objective: To evaluate the clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm-accelerated phase/blast phase (MPN-AP/BP) . Methods: A total of 67 patients with MPN-AP/BP were enrolled from February 2014 to December 2021 at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Their clinical features and prognostic factors were analyzed retrospectively. Results: ① Sixty-seven patients with MPN-AP/BP with a median age of 60 (range, 33-75) years, including 31 males (46.3% ) and 36 females (53.7% ) , were analyzed. Forty-eight patients progressed from primary myelofibrosis (PMF) , and 19 progressed from other myeloproliferative neoplasms (MPNs) , which included polycythemia vera, essential thrombocythemia, and MPN unclassifiable. Patients who progressed from PMF had higher lactate dehydrogenase (LDH) levels than those who progressed from other MPNs (925.95 vs. 576.2 U/L, P=0.011) , and there were higher proportions of patients who progressed from PMF with splenomegaly (81.4% vs. 57.9% , P=0.05) , a myelofibrosis grade of ≥2 (93.6% vs. 63.2% , P=0.004) , and a shorter duration from diagnosis to the transformation to AP/BP (28.7 vs. 81 months, P=0.001) . ② JAK2V617F, CALR, and MPLW515 were detected in 41 (61.2% ) , 13 (19.4% ) , and 3 (4.5% ) patients, respectively, whereas 10 (14.9% ) patients did not have any driver mutations (triple-negative) . Other than driver mutations, the most frequently mutated genes were ASXL1 (42.2% , n=27) , SRSF2 (25% , n=16) , SETBP1 (22.6% , n=15) , TET2 (20.3% , n=13) , RUNX1 (20.3% , n=13) , and TP53 (17.2% , n=11) . The ASXL1 mutation was more enriched (51.1% vs. 21.1% , P=0.03) , and the median variant allele fraction (VAF) of the SRSF2 mutation (median VAF, 48.8% vs. 39.6% ; P=0.008) was higher in patients who progressed from PMF than those who progressed from other MPNs. ③ In the multivariate analysis, the complex karyotype (hazard ratio, 2.53; 95% confidence interval, 1.06-6.05; P=0.036) was independently associated with worse overall survival (OS) . Patients who received allogeneic stem cell transplantation (allo-HSCT) (median OS, 21.3 vs. 3 months; P=0.05) or acute myeloid leukemia-like (AML-like) therapy (median OS, 13 vs. 3 months; P=0.011) had significantly better OS than those who received supportive therapy. Conclusion: The proportions of patients with PMF-AP/BP with splenomegaly, myelofibrosis grade ≥2, a higher LDH level, and a shorter duration from diagnosis to the transformation to AP/BP were higher than those of patients with other Philadelphia-negative MPN-AP/BP. The complex karyotype was an independent prognostic factor for OS. Compared with supportive therapy, AML-like therapy and allo-HSCT could prolong the OS of patients with MPN-AP/BP.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Blast Crisis/drug therapy* ; Primary Myelofibrosis/genetics* ; Prognosis ; Splenomegaly ; Retrospective Studies ; Myeloproliferative Disorders/genetics* ; Mutation ; Leukemia, Myeloid, Acute ; Janus Kinase 2/genetics*

Objective: To explore the molecular features of chronic myelomonocytic leukemia (CMML) . Methods: According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Results: Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (OR=4.129, 95% CI 1.481-11.510, Q=0.007) and TET2 (OR=5.276, 95% CI 1.979-14.065, Q=0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (OR=0.174, 95% CI 0.038-0.791, Q=0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old vs 47 years old, P<0.001), white blood cell count (15.9×10(9)/L vs 4.4×10(9)/L, P<0.001), proportion of monocytes (21.5% vs 15%, P=0.001), and hemoglobin level (86 g/L vs 74 g/L, P=0.014). TET2 mutations (P=0.021) and SRSF2 mutations (P=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (P<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. Conclusion: According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.
Humans ; Aged ; Middle Aged ; Leukemia, Myelomonocytic, Chronic/genetics* ; Prognosis ; Splicing Factor U2AF/genetics* ; Mutation ; Myelodysplastic Syndromes/genetics* ; Leukemia, Myeloid, Acute/genetics*

The pharmaceutical manufacturing model is gradually changing from intermittent manufacturing to continuous manufacturing and intelligent manufacturing. This paper briefly reviewed the supervision and research progress in continuous pharmaceutical manufacturing in China and abroad and described the definition and advantages of continuous pharmaceutical manufacturing. The continuous manufacturing of traditional Chinese medicine(TCM) at the current stage was summarized in the following three terms: the enhancement of the continuity of intermittent manufacturing operations, the integration of continuous equipment to improve physical continuity between units, and the application of advanced process control strategies to improve process continuity. To achieve continuous manufacturing of TCM, the corresponding key technologies, such as material property characterization, process modeling and simulation, process analysis technology, and system integration, were analyzed from the process and equipment, respectively. It was proposed that the continuous manufacturing equipment system should have the characteristics of high speed, high response, and high reliability, "three high(H~3)" for short. Considering the characteristics and current situation of TCM manufacturing, based on the two dimensions of product quality control and production efficiency, a maturity assessment model for continuous manufacturing of TCM, consisting of operation continuity, equipment continuity, process continuity, and quality control continuity, was proposed to provide references for the application of continuous manufacturing technology for TCM. The implementation of continuous manufacturing or the application of key continuous manufacturing technologies in TCM can help to systematically integrate advanced pharmaceutical technology elements and promote the uniformity of TCM quality and the improvement of production efficiency.
Medicine, Chinese Traditional ; Reproducibility of Results ; China ; Quality Control ; Pharmaceutical Preparations

OBJECTIVE: To analyze the effects of ozone (O₃) concentrations measured with different approaches across different seasons on the total number of childhood asthma-related clinical visits, as well as the differentiation of such effects across different groups of patients. METHODS: The outpatient data of three grade A tertiary hospitals in Lanzhou City spanning from 1 January 2014 to 31 December 2017, as well as air pollution and meteorological data during the same period were collected. Considering the nonlinear relationship between O₃ concentrations and the total number of childhood asthma-related clinical visits and meteorological factors, a generalized additive temporal sequence model was employed to analyze the short-term association between changes in O₃ concentrations and the total number of childhood asthma-related clinical visits. Taking into account of the variations in O₃ concentrations within 1 day, this study adopted different measurement approaches to address the three types of O₃ exposures, namely, the maximum 1 h daily concentration (O₃max1h), the maximum 8 h daily concentration (O₃8h) and the mean 24 h daily concentration (O₃24h) as the short term exposure indicators to O₃, followed by a model-based analysis. RESULTS: The increase in short-term exposure levels to O₃ in summer had a significant effect on the increase in the total number of childhood asthma-related clinical visits. With lag0 for the current day, every 10 μg/m³ increase in atmospheric concentration of O₃max1h was associated with an increase in the total number of childhood asthma-related clinical visits by 3.351% (95%CI: 1.231%-5.516%); for every 10 μg/m³ increase in O₃8h concentration, the total number of childhood asthma-related clinical visits increased by 3.320% (95%CI: 0.197%-3.829%); for every 10 μg/m³increase in O₃24h concentration, the total number of childhood asthma-related clinical visits in summer increased by 6.600% (95%CI: 0.914%-12.607%); moreover, an increase in exposure to O₃max1h also led to a significant rise in the total number of childhood asthma-related clinical visits among the males. CONCLUSION The increase in short-term exposure levels to O₃ in summer in Lanzhou City has a significant effect on the increase in the total number of childhood asthma-related clinical visits; O₃max1h is more closely correlated with the increase in the total number of childhood asthma-related clinical visits.
Air Pollutants/analysis* ; Air Pollution/analysis* ; Asthma/etiology* ; China/epidemiology* ; Humans ; Male ; Outpatients ; Ozone/analysis* ; Particulate Matter ; Seasons ; Tertiary Care Centers

Objective: To compare clinical and laboratory features between JAK2 exon12 and JAK2 V617F mutated polycythemia vera (PV) . Method: We collected data from 570 consecutive newly-diagnosed subjects with PV and JAK2 mutation, and compared clinical and laboratory features between patients with JAK2 exon12 and JAK2 V617F mutation. Results: 543 (95.3%) subjects harboured JAK2 V617F mutation (JAK2 V617F cohort) , 24 (4.2%) harboured JAK2 exon12 mutations (JAK2 exon12 cohort) , and 3 (0.5%) harboured JAK2 exon12 and JAK2 V617F mutations. The mutations in JAK2 exon12 including deletion (n=10, 37.0%) , deletion accompanied insertion (n=10, 37.0%) , and missense mutations (n=7, 25.9%) . Comparing with JAK2 V617F cohort, subjects in JAK2 exon12 cohort were younger [median age 50 (20-73) years versus 59 (25-91) years, P=0.040], had higher RBC counts [8.19 (5.88-10.94) ×10(12)/L versus 7.14 (4.11-10.64) ×10(12)/L, P<0.001] and hematocrit [64.1% (53.7-79.0%) versus 59.6% (47.2%-77.1%) , P=0.001], but lower WBC counts [8.29 (3.2-18.99) ×10(9)/L versus 12.91 (3.24-38.3) ×10(9)/L, P<0.001], platelet counts [313 (83-1433) ×10(9)/L versus 470 (61-2169) ×10(9)/L, P<0.001] and epoetin [0.70 (0.06-3.27) versus 1.14 (0.01-10.16) IU/L, P=0.002] levels. We reviewed bone marrow histology at diagnosis in 20 subjects with each type of mutation matched for age and sex. Subjects with JAK2 exon12 mutations had fewer loose megakaryocyte cluster (40% versus 80%, P=0.022) compared with subjects with JAK2 V617F. The median follow-ups were 30 months (range 4-83) and 37 months (range 1-84) for cohorts with JAK2 V617F and JAK2 exon12, respectively. There was no difference in overall survival (P=0.422) and thrombosis-free survival (P=0.900) . Conclusions: Compared with patients with JAK2 V617F mutation, patients with JAK2 exon12 mutation were younger, and had more obvious erythrocytosis and less loose cluster of megakaryocytes.
Adult ; Aged ; Aged, 80 and over ; Bone Marrow/pathology* ; Exons ; Humans ; Janus Kinase 2/genetics* ; Middle Aged ; Mutation ; Mutation, Missense ; Polycythemia Vera/genetics* ; Young Adult

Patrinia villosa, regarding its functions in clearing heat and detoxification and eliminating carbuncles and pus, is widely used as a traditional medicinal herb that contains rich nutrition and substances such as various amino acids, vitamins, and soluble su-gar, and it is also an edible wild herb in Chinese folk tradition for 2 000 years. In 1973, Japanese scholars firstly separated three iridoids from Japanese P. villosa, and by 2021, chemical components such as flavonoids, iridoids, organic acids, triterpenoids, phenylpropanoids, and steroids have been found, which have multiple pharmacological effects, including antioxidant, antitumor, anti-diarrhea, antibacterial, sedative, and liver protection capabilities. Studies indicate that flavonoids, saponins, phenylpropanoids, and triterpenoids in P. villosa are vital substances for its pharmacological activities. However, the quality of this medicinal material cannot be controlled due to the unclear records in ancient books in the past dynasties and different drug use habits in different places, and thus its circulation is chaotic. At present, researchers have used flavonoids, organic acids, phenylpropanoids, triterpenoid saponins, and other compounds to conduct studies in this regard. Therefore, on the basis of the existing literature resources, we comprehensively summarize the chemical constituents, pharmacological activities, and quality control of P. villosa to further provide a reference for the safety and effectiveness of clinical drug use and lay a foundation for the follow-up experimental research.
Patrinia/chemistry* ; Flavonoids/pharmacology* ; Saponins ; Triterpenes/pharmacology* ; Iridoids ; Quality Control