OBJECTIVE To analyze the potential adverse drug interactions （pADIs） of clarithromycin， and establish refined prescription pre-review rules. METHODS Outpatient prescriptions of clarithromycin in combination with other drugs were collected from January 1， 2024 to June 30， 2024 through hospital information system of the Third People’s Hospital of Bengbu. pADIs were identified and their risk severities were graded according to Lexicomp and Micromedex databases. Then， refined prescription pre- review rules for clarithromycin pADIs-related drugs were established according to the identification and risk level results. RESULTS Among 3 046 clarithromycin combined drug prescriptions， 946 cases of pADIs occurred in 812 prescriptions. There were 6， 415 and 525 cases classified as “contraindicated”，“ major” and “moderate”， respectively. The combination drugs with “contraindicated” levels were tamsulosin， rupatadine， domperidone and ticagrelor， while those with “major” levels were mainly theophylline， dexamethasone and amlodipine. Accordingly， 26 refined rules were established， including 4 items of “warning information→prescription interception”， 11 items of “warning information→prescription double signature” and 11 items of “attention information→prescription approval”. CONCLUSIONS There are “contraindicated” and “major” risks associated with clarithromycin and its combination drugs in the hospital， and refined prescription pre-review rules for clarithromycin combined drug prescription have been established successfully.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Humans ; Adolescent ; Fractures, Avulsion ; Fractures, Bone ; Fracture Fixation, Internal ; Ischium/surgery*

Elemene, derived from Curcuma wenyujin, one of the "8 famous genuine medicinal materials of Zhejiang province," exhibits remarkable antitumor activity. It has gained wide recognition in clinical practice for effectiveness on tumors. Dr. XIE Tian, introduced the innovative concept of "molecular compatibility theory" by combining Chinese medicine principles, specifically the "monarch, minister, assistant, and envoy" theory, with modern biomedical technology. This groundbreaking approach, along with a systematic analysis of Chinese medicine and modern biomedical knowledge, led to the development of elemene nanoliposome formulations. These novel formulations offer numerous advantages, including low toxicity, well-defined composition, synergistic effects on multiple targets, and excellent biocompatibility. Following the principles of the "molecular compatibility theory", further exploration of cancer treatment strategies and methods based on elemene was undertaken. This comprehensive review consolidates the current understanding of elemene's potential antitumor mechanisms, recent clinical investigations, advancements in drug delivery systems, and structural modifications. The ultimate goal of this review is to establish a solid theoretical foundation for researchers, empowering them to develop more effective antitumor drugs based on the principles of "molecular compatibility theory".
Humans ; Retrospective Studies ; Antineoplastic Agents/therapeutic use* ; Neoplasms/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Sesquiterpenes/therapeutic use*

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

Objective To evaluate the safety and efficacy of transcatheter arterial chemoembolization(TACE)combined with lenvatinib and camrelizumab in the treatment of advanced hepatocellular carcinoma(HCC).Methods The clinical data of a total of 63 patients with advanced HCC,who received TACE combined with lenvatinib and camrelizumab(triple therapy)or TACE combined with lenvatinib(dual therapy)at the Jingmen Municipal People's Hospital of China between April 2020 and December 2021,were retrospectively analyzed.Triple therapy group had 30 patients,and dual therapy group had 33 patients.The post-treatment tumor response,disease progression-free survival(PFS),overall survival(OS),and the incidence of adverse drug reactions were recorded.Results The median follow-up period of the two groups was 14 months(range of 4-26 months).Compared with the dual therapy group,in the triple therapy group the objective response rate(ORR)was remarkably higher(83.3%vs.57.6%,P=0.026),the disease control rate(DCR)was obviously higher(93.3%vs.69.7%,P=0.039),the median PFS was significantly longer(8.0 months vs.5.0 months,P＜0.01),and the median OS was strikingly longer(24.0 months vs.12.0 months,P=0.004).No statistically significant difference in the incidence of adverse drug reactions existed between the two groups(P＞0.05).Conclusion For the treatment of advanced HCC,TACE combined with lenvatinib and camrelizumab is clinically safe and effective.(J Intervent Radiol,2024,32:57-62)

Objective To compare the effects of two arc(TA)and dual arc(DA)techniques on the dose distribution to the planning target volume(PTV)and organs at risk(OAR)in volumetric modulated arc therapy(VMAT)for lower mid-thoracic esophageal cancer.Methods Ten patients with lower mid-thoracic esophageal cancer who received radiation therapy at some hospital from July 2020 to June 2022 were selected retrospectively.A TA radiation therapy plan and a DA radiation therapy plan were developed for each patient using the Ray Arc module of RayStation 4.7.5.4 planning system,and the two kinds of radiation plans were compared in terms of dosimetric parameters including D2,D5,D50,D95,D98,homogeneity index(HI),conformity index(CI),beam-on time and total monitor unit for PTV and lung V5,V10,V20,V30 and Dmean and heartV30,V40 and Dmean and spine cord Dmax for OAR.SPSS 22.0 was used for statistical analysis.Results TA and DA radiation therapy plans had no significant differences in PTV CI,HI,D2,D5,D50,D95 and beam-on time(P＞0.05),and DA plan had D98 and total monitor unit higher obviously than those of TA plan(P＜0.05).In terms of OARs protection,DA plan had heart V30,V40 and Dmean slightly lower than those of TA plan with non-significantly differences(P＞0.05),while lung V5,V30 and Dmean and spine cordDmax significantly lower(P＜0.05).Conclusion DA technique gains advantages over TA technique in PTV dose distribution and dose to OAR,and the involvement of DA technique in preparing the VMAT plan for esophageal cancer contributes to enhancing the treatment efficacy.[Chinese Medical Equipment Journal,2024,45(1):62-66]

Objective:To investigate the effect of circ_DCAF6 on the proliferation,migration and apoptosis of colorectal cancer cells resistant to cisplatin(DDP)and its possible mechanism.Methods:SW480 and DDP-resistant cells SW480/DDP were cultured in vitro.The expression of circ_DCAF6 and miR-485-3p in the cells was detected by RT-qPCR,and the expression of FOXK1 protein was detected by Western blotting.After si-NC,si-circ_DCAF6,miR-NC,or miR-485-3p was transfected into SW480/DDP cells,or si-circ_DCAF6 and anti-miR-485-3p were co-trans-fected into SW480/DDP cells,respectively,CCK-8 method was used to detect the effect of DDP at different concentrations(0,0.156,0.625,2.5,10,40,160 p g/mL)on the 24 h survival rate of trans-fected cells,and the half inhibitory concentration(IC50 value)was calculated;Cell migration and apoptosis were detected and the regulatory relationship between circ_DCAF6,miR-485-3p and FOXK1 was verified.Results:Compared with SW480 cells,circ_DCAF6 and FOXK1 protein ex-pressions were increased in SW480/DDP cells,while miR-485-3p expression was decreased(P＜0.05).Silencing circ_DCAF6 or overexpression of miR-485-3p inhibited the proliferation and mi-gration of SW480/DDP cells and the expression of FOXK1 protein,increased the sensitivity of SW480/DDP cells to DDP,and promoted cell apoptosis(P＜0.05).Knockdown of miR-485-3p atten-uated the effects of circ_DCAF6 silencing on the malignant phenotype of SW480/DDP cells.circ_DCAF6 could target miR-485-3p;FOXK1 was the target gene of miR-485-3p.Conclusion:Silencing circ_DCAF6 could inhibit the proliferation and migration of SW480/DDP cells and promote cell apoptosis.Its mechanism of action is related to the regulation of miR-485-3p/FOXK1 axis.