The dosage-efficacy/toxicity relationship of the 50% alcohol extracts of Polygonum multiflorum was comparatively investigated on either normal or CCl4-induced chronic liver injury rats, by determining the general condition, serum biochemical indices and liver histopathology, coupled with the factor analysis. The dosages were 10 and 20 g raw materials per kg body weight. Compared with the normal control group, the normal high dose group showed significant increases of the serum alanine transaminase (ALT), total bilirubin (TBIL), high mobility group box 1 (HMGB-1) and interleukin-1β (IL-1β) (P < 0.05 or P < 0.01), as well the frequent incidences of inflammatory cell infiltration, hepatic sinus enlargement and fiber stripes formation in histopathological sections. Compared with the model control group, the model low dose group showed significant declines of serum ALT, aspartate transaminase (AST) and total bile acid (TBA) (P < 0.05), as well the alleviation of vacuoles of hepatocytes, but no amelioration of the inflammatory cell infiltration and fibrous tissue hyperplasia; moreover, the model high dose group showed significant degeneration declines of serum HMGB-1, tumor necrosis factor-α (TNF-α) and IL-1β (P < 0.05, P < 0.01), as well the evident alleviation of vacuoles degeneration of hepatocytes, inflammatory cells infiltration and fibrosis degree. The factor analysis showed that the low dosage treatment had almost neither injuring effect on the normal rats nor protective effect on the model rats; while the high dosage treatment showed observable injuring effect on the normal rats, expressed by the significant increases of the factor-1 (HMGB-1, TNF-α and IL-1β as the main contributors) and factor-2 (TBIL, ALT and TBA as the main contributors) relative to the normal control group. The liver protective effect of the high dosage treatment could be observed with the significant reduction of the factor-1, indicating the effective alleviation of the expression of inflammatory cytokines. In conclusion, it could illustrated the phenomenon of symptom-based prescription theory of Polygonum multiflorum on rat livers: the high dosage of the herb had either an injuring effect on normal rats, or a therapeutic effect on the rats with chronic liver injury.

The liver injury induced by Polygonum multiflorum Thunb. (PM) was investigated based on idiosyncratic hepatotoxicity model co-treated with lipopolysaccharide (LPS) at a non-hepatotoxic dose. Sprague-Dawley (SD) rats were intragastrically administered with three doses (18.9, 37.8, 75.6 g crude drug per kg body weight) of 50% alcohol extracts of PM alone or co-treated with non-toxic dose of LPS (2.8 mg·kg(-1)) via tail vein injection. The plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were assayed and the isolated livers were evaluated for histopathological changes. The dose-toxicity relationships of single treatment of PM or co-treatment of LPS were investigated comparatively to elucidate the idiosyncratic hepatotoxicity of PM. The results showed that no significant alterations of plasma ALT and AST activities were observed in the groups of solo-administration of LPS (2.8 mg·kg(-1), i.v.) or different dosage (18.9, 37.8 and 75.6 g·kg(-1), i.g.) of PM, compared to normal control group (P > 0.05); while significant elevations were observed in the co-administration groups of PM and LPS. Treatment with LPS alone caused slight infiltration of inflammatory cells in portal area but no evident hepatocytes injury. Co-treatment with LPS and PM (75.6 g·kg(-1), i.g.) caused hepatocyte focal necrosis, loss of central vein intima and a large number of inflammatory cell infiltration in portal areas. When further reduce the dosage of PM, significant increases of plasma ALT and AST activities (P < 0.05) were still observed in co-administration groups of LPS and PM (1.08 or 2.16 g·kg(-1)), but not in LPS or PM solo-administration groups. Nevertheless, the co-treatment of low dosage of PM (0.54 g·kg(-1)) with LPS did not induce any alteration of plasma ALT and AST. In conclusion, intragastric administration with 75.6 g·kg(-1) of PM did not induce liver injury in normal rats model; while the 2 folds of clinical equivalent dose of PM (1.08 g·kg(-1)) could result in liver injury in the LPS-based idiosyncratic hepatotoxicity model, which could be used to evaluate the idiosyncratic hepatotoxicity of PM.

Objective:To analyze the selection of outcome indicators for randomized controlled trials (RCT) on exercise rehabilitation in patients with atrial fibrillation (AF), promote the construction of the core outcome set and provide reference for the research design of subsequent RCT.Methods:The RCT literature related to exercise rehabilitation of patients with atrial fibrillation was systematically searched from CNKI, Wanfang, VIP, PubMed, Web of Science, Embase and Cochrane Library databases, and the search period was from establishment of the databases until July 31, 2023. After literature screening, Cochrane Risk of Bias Assessment Tool was used for quality evaluation, information extraction, classification of outcome indicators, frequency of use statistics, analysis and extraction of current shortcomings in the selection of outcome indicators, and corresponding suggestions were proposed.Results:A total of 32 articles were included, and 19 RCT were evaluated twice for outcome measures. The number of outcome measures ranged from 2 to 17, with 10 RCT setting outcome measures according to primary and secondary criteria and 6 RCT setting safety outcome measures. A total of 96 outcome indicators were extracted in this study, total 266 frequency, which could be divided into 4 categories, such as safety evaluation (18 times), clinical response (75 times), patient-reported outcomes (68 times) and laboratory and other examination (105 times) .Conclusions:Existing RCT outcome indicators of exercise rehabilitation in patients with atrial fibrillation emphasize the changes in subjective feelings and objective indicators of individuals, covering four aspects such as the physical condition, exercise ability, quality of life and psychological status of individuals. However, there is a lack of uniform standards and the safety evaluation indicators are fewer. The categories of exercise rehabilitation indicators for atrial fibrillation patients extracted in this paper can provide a reference for the design of future RCT studies and promote the generation of higher quality evidence-based medical evidence.

Purpose To study the consistency of NTRK fu-sion gene in the thyroid carcinoma detected by four technology platforms:immunohistochemistry,DNA-based NGS,FISH and qRT-PCR.Methods NTRK fusion gene was detected by FISH,immunohistochemical(IHC),DNA-based NGS and qRT-PCR in a same group of 40 clinical cases(among them,31 cases were thyroid cancer samples).Results In a group of 31 thyroid cancer cases detected by four techniques,compared with FISH,the sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV)and total coincidence rate(TCR)of IHC was 100%(9/9),90.9%(20/22),81.8%(9/11),100%(20/20),93.5%(29/31),respectively.The PPV of IHC was poor.The sensitivity,specificity,PPV,NPV and TCR of DNA-based NGS was 44.4%(4/9),100%(22/22),100%(4/4),81.5%(22/27),83.9%(26/31),respectively,and the sensitivity was poor.The TCR of qRT-PCR was 100%(31/31).Compared with FISH,Kappa value of IHC,DNA-based NGS and qRT-PCR was 0.853,0.532 and 1.000,respectively.Of the 40 clinical cases,the concordance between qRT-PCR and FISH was observed for 39 samples,for the qRT-PCR assay did not cover the NTRK fusion type(LM-NA:exon4-NTRK1:exon10).Compared with FISH,the coinci-dence rate of qRT-PCR was highest.Conclusion The RNA-based assay of qRT-PCR does have the advantages of high sensi-tivity and high specificity,and may be an optimal scheme for routine clinical detection of NTRK fusion variation in thyroid cancer in pathology department.

Objective:To investigate the clinicopathological characteristics, immunophenotype, molecular genetic characteristics and prognosis of the metaplastic thymoma (MT).Methods:The clinicopathological and follow-up data of five MT cases were collected at Fujian Provincial Hospital from 2008 to 2019. Immunohistochemical staining and MAML2 gene detection were performed, and the relevant literature was reviewed.Results:There were 2 males and 3 females, aged 36-64 years (mean age 52 years). The tumors ranged 3.2-7.3 cm in the greatest diameter (average 5.1 cm).Microscopically, the tumor showed a biphasic pattern with epithelial cells merging gradually with the spindle cell component. The two areas transited to each other or had obvious boundary. Both components showed mild atypia. No mitosis was observed in either area, and a small number of lymphocytes were observed in the stroma. Immunohistochemical staining showed that epithelioid cells were positive for CKpan, p63 and E-cadherin. Spindle cells were positive for vimentin and EMA, while the Ki-67 index was less than 5%, and lymphocytes were negative for TdT. MAML2 gene apart signal was detected in two of the cases (2/4) that were tested by FISH.Conclusions:MT is a low-grade malignant epithelioid thymic tumor. Its diagnosis and differential diagnosis are dependent on the morphological characteristics, immunohistochemical staining and MAML2 gene detection. The primary treatment option is surgical resection, with an overall good prognosis.

Objective:To investigate the genetic abnormality and protein expression of C-MYC and PD-L1 in the patients with ALK-negative anaplastic large cell lymphoma (ALK －ALCL), and to explore their roles in the pathogenesis of ALK －ALCL and their relationship with clinicopathological characteristics. Methods:Thirty-seven cases of ALK －ALCL diagnosed at Fujian Provincial Hospital from January 2003 to January 2017 were selected. Fluorescence in situ hybridization (FISH) was used to detect the genetic abnormality of C-MYC and PD-L1. The expression of C-MYC and PD-L1 proteins was detected by immunohistochemistry. The relationship between C-MYC and PD-L1 genes′ abnormalities and protein expression was analyzed, as well as their associations with various clinicopathological parameters. Results:Among the 37 ALK －ALCL patients, 17 (45.9%) were positive for C-MYC protein, and 14 (37.8%) were positive for PD-L1 protein. There was a significant correlation between C-MYC protein and PD-L1 protein ( r=0.990, P=0.014). The protein expression of C-MYC and PD-L1 (versus negative) was associated with the clinical stage of ALK －ALCL, respectively. The international prognosis index (IPI) in high-risk group was higher than that in the low-risk group ( P<0.05). FISH test showed that 9 (24.3%) of the 37 cases had amplification of C-MYC gene, and no translocation of C-MYC gene was found in any of the cases. Amplification of PD-L1 gene was found in only 2 cases (5.4%). The 3-year overall survival rate of the C-MYC or PD-L1 immunohistochemistry-positive cases was significantly lower than those of the C-MYC or PD-L1 negative cases ( P<0.01 and P<0.05), respectively. Conclusion:The expression of C-MYC and PD-L1 proteins are related to the clinical stage, IPI and overall survival rate of ALK －ALCL. Thus, it can be used to assess the disease′s aggressiveness and to predict the prognosis of ALK －ALCL. The expression of PD-L1 in ALK －ALCL may be regulated by C-MYC, thus suggesting a possible design of combined C-MYC targeted therapy and immune checkpoint blocking for some ALK －ALCL patients.

Objective: To investigate the effect of lipiodol as embolization agents in liver, after transcatheter arterial chemoembolization, on dose calculation under the carbon ion treatment plan. Methods: The actual relative linear stopping powers(RLSP)in pure lipiodol, pure gel and lipiodol-gel mixture, together with the correctd RLSPs from their CT images, were compared.In seven typical cases with lipiodol deposition area, carbon ion treatment plan was performed for the original lipiodol images.Successively on the basis of analysis that has made, the RLSP in lipiodol deposition area was corrected to be as in normal liver tissue, for which the carbon ion treatment plan was again performed.A comparison was made of differences in water equivalent depth (WED) and dose distribution on different CT images. Results: The RLSP value corrected according to CT image HU value, lipiodol, and lipiodol-gel mixture may increase by 4.6%-139.0% compared with the measured value. In seven typical cases, deposited lipiodol can cause WED to increase by (0.89±0.41) cm along the field track and RBE by(3.83±1.71)Gy within the 1 cm of distal area of target. Conclusions In order to improve the accuracy of dose distribution calculation, the HU value and/or RLSP in deposited lipiodol area in liver after transcatheter arterial chemoembolization should being corrected to be as in the normal liver tissue.

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts' discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.
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