Research progress in immune-related liver injury caused by immune checkpoint inhibitors / 国际生物医学工程杂志

In recent years, immune checkpoint inhibitors (ICIs) have made great progress in the treatment of tumor patients, prolonging their survival. However, the expansion of immunity against tumors with ICIs may also cause an imbalance in immune tolerance, leading to immune-related adverse events (irAEs). Immune-mediated liver injury caused by ICIs (ILICI) is one of the more common types of irAEs. In this review paper, the definition, epidemiology, risk factors, pathogenesis, pathology, clinical manifestations, treatment, recurrence, and re-treatment of ILICI were summarized to provide a basis for clinical diagnosis and treatment.

Progress of the development of anti-COVID-19 drugs / 药学学报

Since the outbreak of the novel coronavirus (SARS-CoV-2) disease COVID-19 (also known as 2019-nCoV) caused by SARS-CoV-2 in the end of 2019, it has spread rapidly in worldwide. Besides developing effective vaccines, it is urgent to develop safe and effective anti-SARS-CoV-2 drugs to fight this disease. Paxlovid, molnupiravir, sotrovimab and bebtelovimab are urgently authorized by FDA have been proved to be effective against Omicron. This manuscript mainly reviews the recent progress of effective inhibitors against the virus in the world, including receptor inhibitors, antibodies, natural product inhibitors, synthetic inhibitors and broad-spectrum antiviral drugs that are effective against other RNA viruses.

Construction and Application of Liver Injury Risk Prediction Model of Chinese Medicinals based on Indirect Toxicity / 中医杂志

ObjectiveTo explore and establish the liver injury risk prediction model of indirect toxicity of Chinese medicinals under the condition of compound formulas， and provide new ideas and methods for the study of evaluation of liver injury of Chinese medicinals based on indirect toxicity. MethodsTaking Buguzhi （Fructus Psoraleae） pre-parations as model drug， the combined Chinese medicinals with Buguzhi （Fructus Psoraleae） of high frequency are screened out， and their components and action targets were obtained through TCMSP， TCMIP and PharmMapper databases. The association strength value and risk value of Chinese medicinals that acted on the nuclear factor κB （NF-κB） pathway were analyzed. For those having greater values than the median association strength value and risk value were regarded as indirect Chinese medicinals of liver injury risk. In this way， a prediction model of liver injury risk of Chinese medicinals was constructed based on immune activation-related indirect liver injury process （taking NF-κB pathway as an example）. And verification of the prediction model was performed using Heshouwu （Radix Polygoni Multiflori） preparations. ResultsThe prediction model of liver injury risk based on important immunoactivated pathway （taking NF-κB pathway as an example） found that Yinyanghuo （Herba Epimedii） （association strength value = 0.18， risk value = 0.25） was a Chinese medicinal with potential risk of indirect liver injury within Buguzhi （Fructus Psoraleae） prepartions， which may increase the risk of liver injury by positively regulating Bruton's tyrosine kinase （Btk） and protein kinase C theta （PKCθ） on NF-κB pathway. Further verification of prediction model by Heshouwu （Radix Polygoni Multiflori） preparations showed that Buguzhi （Fructus Psoraleae） （association strength value = 0.25， risk value = 0.33） and Tusizi （Semen Cuscutae） （Semen Cuscutae， association strength value = 0.34， risk value = 0.33） may increase the liver injury risk of Heshouzu. ConclusionThe liver injury risk prediction model of indirect toxicity of Chinese medicinals has been constructed in this study， providing metho-dological reference for the identification of Chinese medicinals of indirect liver injury risk under the condition of compound formulas.

Discrimination of quality markers of Shujin Huoxue Capsules based on five principles coupled with cobweb model / 中国中药杂志

The quality markers(Q-markers) of Shujin Huoxue Capsules were comprehensively discriminated based on the five principles of transfer and traceability, specificity, compatibility, effectiveness and measurability. The compounds that could be transferred from the original medicinal materials to the preparation were selected with the principle of transfer and traceability. The specific components in the prescription were screened by reviewing literature with the principle of specificity. According to the principle of compatibility, the attributes of compounds were evaluated by the sovereign, minister, assistant and guide combination rules of the original medicinal materials in the prescription. According to the principle of measurability, the measurable components were summarized by reference to the pharmacopoeia and literature combined with the content. The mechanism of Shujin Huoxue Capsules in the treatment of osteoporosis was studied through network pharmacology based on the principle of effectiveness, which was the evaluation index of effectiveness. The chemical components screened out above were regarded as candidate Q-markers, and the cobweb model was plotted to obtain the comprehensive score of Q-markers. Hydroxysafflor yellow A, trachelosid, eleutheroside B, α-cyperone, protocatechuic acid, protocatechualdehyde and 4-methoxy salicylaldehyde were discriminated as the Q-markers of Shujin Huoxue Capsules based on the five principles combined with cobweb model.

Comparison of the characteristics of NK cells after two different methods of expansion and observation of the clinical efficacy in patients who relapsed post allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To explore the differences in the biological effects of different expansion systems on natural killer (NK) cells, as well as the safety and preliminary clinical efficacy in the treatment of patients with recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Peripheral blood cells from healthy donors were stimulated with either CD3 combined with CD52 or K562 feeder cells loaded with IL-21/4-1BB to induce NK cell expansion. Changes in the NK cell phenotype, cytokine secretion, and cytotoxicity before and after expansion were detected. We also evaluated the safety and clinical efficacy of two different expansion strategies for patients received NK infusion. Results: Compared with the CD3/CD52 monoclonal antibody amplification system, the feeder cell expansion group had a higher purity of NK cells and higher expression ratios of NK cell surface activation receptors such as DNAM-1 and NKp30, while inhibitory receptor CTLA-4 expression was low and NKG2D/CD25/CD69/ Trail/PD-1/TIM-3/TIGIT had no statistically significant differences between the groups. Further functional results showed that the expression level of KI67 in NK cells after expansion in the two groups increased significantly, especially in the feeder cell expansion group. Simultaneously, the perforin and granzyme B levels of NK cells in the feeder cell expansion group were significantly higher than in the CD3/CD52 expansion group. A retrospective analysis of eight patients who received monoclonal antibody-expanded NK cell reinfusion and nine patients with trophoblast cell-expanded NK cell reinfusion was done. The disease characteristics of the two groups were comparable, NK cell reinfusion was safe, and there were no obvious adverse reactions. Clinical prognostic results showed that in the CD3/CD52 monoclonal antibody amplification group, the MRD conversion rate was 50% (2/4) , and the feeder cell expansion group was 50% (3/6) . After 5 years of follow-up from allo-HSCT, three patients in the monoclonal antibody expansion group had long-term survival without leukemia, and the remaining five patients had died; two patients died in the feeder cell expansion group, and the other six patients had long-term survival. Six cases had GVHD before NK cell reinfusion, and GVHD did not aggravate or even relieved after NK cell reinfusion. Conclusions: Preliminary results show that the biological characteristics of NK cells with diverse expansion strategies are significantly different, which may affect the clinical prognosis of patients with recurrence or persistent minimal residual disease after HSCT. The two groups of patients treated with NK cells from different expansion strategies had no obvious adverse reactions after NK cell infusion, but efficacy still needs to be further confirmed.

Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience / 中华血液学杂志

Objective: To explore the safety and short-term efficacy of venetoclax combined with azacitidine (Ven+AZA) in previously untreated patients unfit for standard chemotherapy and patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) in China. Methods: A retrospective study was conducted in 60 previously untreated patients unfit for standard chemotherapy and patients with R/R AML who received Ven+ AZA (venetoclax, 100 mg D1, 200 mg D2, 400 mg D3-28; azacitidine, 75 mg/m(2) D1- 7) at the Peking University Institute of Hematology from June 1, 2019 to May 31, 2021. The incidence of adverse events, complete remission (CR) /CR with incomplete hematological recovery (CRi) rate, objective remission rate (ORR) , and minimal residual disease (MRD) status in patients with different risk stratification and gene subtypes were analyzed. Results: The median age of the patients was 54 (18-77) years, 33 (55.0%) were males, and the median follow-up time was 4.8 (1.4-26.3) months. Among the 60 patients, 24 (40.0%) were previously untreated patients unfit for standard chemotherapy, and 36 (60.0%) were R/R patients. The median mumber cycles of Ven+AZA in the two groups were both 1 (1-5) . According to the prognostic risk stratification of the National Comprehensive Cancer Network, it was divided into 8 cases of favorable-risk, 2 cases of intermediate risk, and 14 cases of poor-risk. In previously untreated patients unfit for standard chemotherapy, after the first cycle of Ven+AZA, 17/24 (70.8%) cases achieved CR/CRi, 3/24 (12.5%) achieved partial remission (PR) , and the ORR was 83.3%. Among them, nine patients received a second cycle chemotherapy and two received a third cycle. Among CR/CRi patients, 8/17 (47.1%) achieved MRD negativity after two cycles of therapy. In the R/R group, after the first cycle of Ven+AZA, 21/36 (58.3%) cases achieved CR/CRi (7/21 achieved MRD negativity) , 3 achieved PR, and the ORR was 66.7%. Among R/R patients, 12 were treated for more than two cycles. There were no new CR/CRi patients after the second treatment cycle, and 14 cases (66.7%) achieved MRD negativity. According to the time from CR to hematological recurrence, the R/R group was divided into 12 cases in the favorable-risk group (CR to hematological recurrence ≥18 months) and 24 in the poor-risk group (CR to hematological recurrence<18 months, no remission after one cycle of therapy, and no remission after two or more cycles of therapy) . Eleven of 24 (45.8%) cases achieved CR/CRi after one cycle of Ven+AZA in the poor-risk R/R group, and 10 of 12 (83.3%) achieved CR/CRi in the favorable-risk R/R group, which was significantly superior to the poor-risk group (P=0.031) . After one cycle of treatment, 13 patients with IDH1/2 mutations and 4 that were TP53-positive all achieved CR/CRi. The CR/CRi rate of 18 patients with NPM1 mutations was 77.8%. Five patients with RUNX1-RUNX1T1 combined with KIT D816 mutation (two initial diagnoses and three recurrences) had no remission. Ven+ AZA was tolerable for AML patients. Conclusion: Ven+AZA has acceptable safety in previously untreated patients unfit for standard chemotherapy, patients with R/R AML can achieve a high response rate, and some patients can achieve MRD negativity. It is also effective in NPM1-, IDH1/IDH2-, and TP53-positive patients. The long-term efficacy remains to be observed.

A risk score system for stratifying the risk of relapse in B cell acute lymphocytic leukemia patients after allogenic stem cell transplantation / 中华医学杂志(英文版)

BACKGROUND@#For patients with B cell acute lymphocytic leukemia (B-ALL) who underwent allogeneic stem cell transplantation (allo-SCT), many variables have been demonstrated to be associated with leukemia relapse. In this study, we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT.@*METHODS@#A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People's Hospital from December 2010 to December 2015 were enrolled in this retrospective study. We aimed to evaluate the factors associated with transplant outcomes after allo-SCT, and establish a risk score to identify patients with different probabilities of relapse. The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables.@*RESULTS@#All patients achieved neutrophil engraftment, and 95.4% of patients achieved platelet engraftment. The 5-year cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), and non-relapse mortality were 20.7%, 70.4%, 65.6%, and 13.9%, respectively. Multivariate analysis showed that patients with positive post-transplantation minimal residual disease (MRD), transplanted beyond the first complete remission (≥CR2), and without chronic graft-versus-host disease (cGVHD) had higher CIR (P  < 0.001, P = 0.004, and P  < 0.001, respectively) and worse LFS (P  < 0.001, P = 0.017, and P  < 0.001, respectively), and OS (P  < 0.001, P = 0.009, and P  < 0.001, respectively) than patients without MRD after transplantation, transplanted in CR1, and with cGVHD. A risk score for predicting relapse was formulated with the three above variables. The 5-year relapse rates were 6.3%, 16.6%, 55.9%, and 81.8% for patients with scores of 0, 1, 2, and 3 (P  < 0.001), respectively, while the 5-year LFS and OS values decreased with increasing risk score.@*CONCLUSION@#This new risk score system might stratify patients with different risks of relapse, which could guide treatment.

Clinical and immunological characteristics of myositis complicated with thromboembolism / 北京大学学报(医学版)

OBJECTIVE@#To investigate and analyse the clinical and immunological features of patients with myositis complicated with thromboembolism.@*METHODS@#We identified a cohort of 390 myositis patients diagnosed with myositis admitted to People's Hospital of Peking University from 2003 to 2019. The patients were retrospectively enrolled in this investigation. According to the outcome of the color Doppler ultrasound, CT pulmonary angiography, pulmonary ventilation and perfusion scan patients were divided into myositis with and without thromboembolism group. Demographic, clinical (heliotrope rash, Gottron's sign/papules, periungual erythema, skin ulceration, subcutaneous calcinosis, Mechanic's hands, myalgia, interstitial lung disease, pulmonary arterial hypertension), laboratory, immunological [anti-autoantibodies including melanoma differentiation associated gene 5 (anti-MDA5), anti-Mi-2, anti-transcription intermediary factor-1γ (anti-TIF-1γ, anti-nuclear matrix protein 2 (anti-NXP2), anti-small ubiquitin-like modifier activating enzyme (anti-SAE), anti-synthetase], imaging and therapeutic status data of the patients at the diagnosis of myositis with and without thromboembolism were collected and the differences in these data were analyzed. Logistic regressive analysis was used to identify the risk factors of thromboembolism.@*RESULTS@#In the retrospective study, 390 myositis patients were investigated. The mean age of onset was (49.6±13.4) years, male to female ratio was 0.31 :1. Thromboembolism was identified in 4.62% (18/390) of the myositis patients, which was lower than the published reports. Out of 18 patients with thromboembolism, 55.6% (10/18) of them were deep venous thrombosis, followed by cerebral infarction (22.2%, 4/18), pulmonary embolism (11.1%, 2/18), renal artery embolism (5.6%, 1/18) and embolism of upper extremity (5.6%, 1/18). Fifty percent of thromboembolism events occurred 6 months after the diagnosis of myositis, 38.9% of thromboembolism events occurred 6 months within the diagnosis of myositis, 11.1% of thromboembolism events occurred 6 months before the diagnosis of myositis. As compared with the myositis patients without thromboembolism, the myositis patients complicated with thromboembolism were older [(58.3±11.7) years vs. (49.3±13.4) years, P=0.006]. C-reaction protein (CRP) (12.2 mg/L vs. 4.1 mg/L, P < 0.001), ferritin (20 085.5 μg/L vs. 216.6 μg/L, P < 0.001) and D-dimer (529.0 μg/L vs. 268.0 μg/L, P=0.002) were significantly higher in thromboembolism group. Diabetes (44.4% vs. 16.4%, P=0.006), coronary heart disease (22.2% vs. 3.0%, P=0.003) and surgery (16.7% vs. 3.5%, P=0.032) were observed more common in thromboembolism group than those without thromboembolism. Activated partial thromboplastin time (APTT) (26.9 s vs. 28.7 s, P=0.049) and albumin (32.4 g/L vs. 36.5 g/L, P=0.002) was lower in thromboembolism group. The risk factors of thromboembolism in the myositis patients were low level of albumin (OR=0.831, 95%CI: 0.736-0.939, P=0.003), diabetes (OR=4.468, 95%CI: 1.382-14.448, P=0.012), and coronary heart disease (OR=22.079, 95%CI: 3.589-135.837, P=0.001) were independent significant risk factors for thromboembolism in the patients with myositis. There was no significant difference in clinical manifestations, myositis-specific antibodies or myositis-associated antibodies between the two groups.@*CONCLUSION@#Thromboembolism is a complication of myositis. Lower levels of albumin, diabetes, and coronary heart disease might be risk factors of thromboembolism in myositis patients.

Discovery of phthalides with vasodilating activity in stems and leaves of Ligusticum chuanxiong / 中草药

Objective: To study the phthalides with vasodilating activity of alcohol extracts from stems and leaves of Ligusticum chuanxiong. Methods: Compounds were isolated by extensive chromatographic techniques including MCI, silica gel, Sephadex LH-20, ODS, and semi-preparative HPLC. The vasodilating effect of phthalide and dimer phthalide on thoracic aortic ring in vitro was investigated. Results: Ten phthalides were isolated and identified, and their structures were elucidated as Z-3-butylidenephthalide (1), senkyunolide-E (2), Z-senkyunolide-H (3), (3Z,7β)-3-butenyl-7-hydroxy-4,5,6,7-tetrahydrophthalide (4), neoligustilide (5); Z,Z’-3.3’a,7.7’a-diligustilide (6), 3Z,3Z’-6,8’,7,3’-diligustilide (7), Z-tokinolide A (8), (3’Z)-(3S,8R,3a’S,6’R)-4,5-dehydro-3.3’a,8.6’-diligustilide (9), and (3Z)-(3aR,6S,3’R,8’S)-3a.8’,6.3’-diligustilide (10). Compound 1, 6-9 significantly reduced the strain of thoracic aortic ring in KCl preconstricted rats. The diastolic rate of compounds 6-8 were 60%, 52% and 70% at the highest concentrations (12 μmol/L), respectively. The EC50 was 9.46, 11.86 and 8.73 μmol/L, respectively. Firstly isolated from the stems and leaves of L. chuanxiong. Compounds 6, 8 are firstly isolated from L. chuanxiong. The test compounds could dilate blood vessels, and the activity of dimer phthalide was better than that of phthalide.

Predictive factors for the clinical effect of PD-1/PD-L1 checkpoint inhibitors in treatment of hepatocellular carcinoma / 临床肝胆病杂志

At present, there is still a lack of uniform treatment strategies for hepatocellular carcinoma (HCC). Immunotherapy, especially PD-1/PD-L1 checkpoint inhibitors, is a novel therapy for HCC and can bring survival benefits to patients with advanced HCC. However, research data show that only a small number of HCC patients can benefit from this treatment regimen. To date, few biomarkers have been reported to predict the clinical effect of PD-1/PD-L1 checkpoint inhibitors in HCC patients. This article reviews the biomarkers studied for HCC and other tumors and explores the possible predictive factors for the clinical effect of PD-1/PD-L1 checkpoint inhibitors in HCC, in order to optimize the selection of treatment population and improve the clinical effect of PD-1/PD-L1 checkpoint inhibitors in the treatment of HCC.

Role of NRF2 signaling pathway in trichloroethylene-induced oxidative stress in HepG2 cells / 中国职业医学

OBJECTIVE: To investigate the role of nuclear factor erythroid-2-related factor 2(NRF2) signaling pathway in trichloroethylene(TCE) induced oxidative stress in human liver cancer HepG2 cells. METHODS: HepG2 cells in the exponential growth phase were randomly divided into control group and low-, medium-and high-dose groups, and the cells were stimulated with TCE at the final concentrations of 0, 2, 4 or 8 mmol/L respectively for 24 hours. After TCE exposure, the cells were collected. The activity of superoxide dismutase(SOD) was measured by 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulphenyl)-2 h-tetrazole monosodium salt method.The activities of catalase(CAT) and glutathione peroxidase(GSH-Px) were detected by enzymatic method. The level of malondialdehyde(MDA) was detected by thiobarbituric acid method. The level of 8-hydroxydeoxyguanosine(8-OHDG) was detected by enzyme-linked immunosorbent assay. The mRNA expression of NRF2, heme oxygenase(HO1), glutamate-cysteine ligase catalytic subunit(GCLC), NAD(P) quinone oxidoreductase 1(NQO1) were detected by real-time polymerase chain reaction and the protein expression of NRF2, HO1, GCLC, NQO1 were detected by Western blotting. RESULTS: The activity of CAT in HepG2 cells decreased in the 3 doses drug exposure groups(all P<0.05). The activity of GSH-Px increased(all P<0.05), while the level of MDA in HepG2 cells decreased in low-dose group compared with the control group(P<0.05). There was no statistical significance in SOD activity and 8-OHDG level of HepG2 cells among these 4 groups(all P>0.05). The mRNA and protein relative expression of NRF2 and GCLC in HepG2 cells decreased in the low-and medium-dose groups(all P<0.05) compared with the control group. The mRNA relative expression of HO1 decreased(all P<0.05). The HO1 protein relative expression of HepG2 cells increased in low-dose group compared with the control group(P<0.05). The mRNA and protein relative expression of NQO1 in low-dose group increased(both P<0.05). The protein relative expression of HO1 in HepG2 cells in medium-dose group was lower than that in control group(P<0.05).The mRNA and protein relative expression levels of NRF2 and NQO1 increased in HepG2 cells of high-dose group(all P<0.05) and the mRNA relative expression of HO1 increased in HepG2 cells of high-dose group(all P<0.05) compared with the other 3 groups. CONCLUSION: The low and medium dose TCE stimulation can cause oxidative stress in HepG2 cells and decrease the antioxidant enzyme activity. The high dose TCE stimulation to HepG2 cells can activate NRF2 signaling pathway, thus upregulating the expression of downstream antioxidant enzymes HO1, GCLC and NQO1, and relieving the oxidative damage caused by TCE.

Effect of lyciumbarbarum polysaccharide on sex hormone and ovarian estrogen receptor in rats exposed to n-hexane / 中国职业医学

OBJECTIVE: To investigate the effect of n-hexane on the level of sex hormones and expression of estrogen receptor(ER) in rats and the protective effect of Lyciumbarbarum polysaccharide(LBP) on n-hexane-induced reproductive toxicity. METHODS: Based on factorial design model of 4×2, specific pathogen free adult female SD rats were divided into control group and low-, medium-and high-n-hexane exposure groups, and each group was divided into non-LBP intervention and LBP intervention sub-group. There were 8 subgroups with 6 rats in each group. On the first day, the rats in the 4 groups were given intraperitoneal injection of n-hexane at 0, 675, 1 350 and 2 700 mg/kg body weight, respectively. On day 2-4, the rats in the non-LBP intervention subgroup were given intragastric administration of 0.9% sodium chloride solution, and the rats in the LBP intervention subgroup were given intragastric administration of LBP at 50 mg/kg body weight once a day. On the fifth day, all animals were sacrificed, and the levels of follicle stimulating hormone(FSH), luteinizing hormone(LH), estradiol, progesterone were detected by enzyme linked immunosorbent assay. The mRNA expression of Erα, Erβ and G protein coupled estrogen receptor 1(Gper1) was detected by real time fluorescence polymerase chain reaction, and the expression of ERα, ERβ and GPER1 protein was detected by Western blotting. RESULTS: i) In the absence of LBP intervention(i.e. simple n-hexane exposure), there was no significant difference in the level of serum FSH, LH, estradiol and progesterone in the 4 groups(P>0.05). The relative expression of Erβ mRNA in ovary of low dose group decreased, while the relative expression of proteins of ERα and GPER1 increased(P<0.05) when compared with the control group. The relative expression of Erα mRNA and GPER1 protein in the ovary of medium-and high-dose groups increased(P<0.05), while the relative expression of Erβ, Gper1 mRNA and ERβ protein decreased(P<0.05). The relative expression of ERα protein in ovary of high-dose group increased(P<0.05). ii) At the same dose of n-hexane exposure, the relative expression of Erα mRNA in ovary of rats in low dose group increased(P<0.05), while the relative expression of ERβ and GPER1 protein decreased in LBP intervention group compared with the no LBP intervention group(P<0.05). The relative expression of ERα and GPER1 protein in ovary of medium dose group increased(P<0.05), while the relative expression of Gper1 mRNA and GPER1 protein in ovary of high dose group decreased in LBP intervention group compared with the no LBP intervention group(P<0.05). CONCLUSION: n-Hexane can up-regulate the expression of ERα and GPER1 in rat ovary, but has no significant effect on female endocrine system. LBP may play a protective role in female reproductive system by up-regulating the expression of ERα and GPER1.

Value of capsule endoscopy in children with small intestinal diseases with hematochezia as the chief complaint / 中国当代儿科杂志

OBJECTIVE@#To evaluate the value of capsule endoscopy in children with small intestinal diseases with hematochezia as the chief complaint.@*METHODS@#A retrospective analysis was performed on the clinical data and capsule endoscopy findings of 93 children with hematochezia who were admitted to Children's Hospital of Fudan University from May 2015 to January 2019 and underwent capsule endoscopy. According to the capsule endoscopy findings of the jejunum and the ileum, they were divided into a positive lesion group with 39 patients and a negative lesion group with 54 patients. Related clinical data and the features of lesion on capsule endoscopy were analyzed for the two groups.@*RESULTS@#There were no significant differences in age, sex, duration of capsule endoscopy, gastric transit time, and small intestinal transit time between the positive lesion and negative lesion groups (P>0.05). The positive lesion group had a significantly lower level of hemoglobin than the negative lesion group (P<0.05). Hemoglobin level was negatively correlated with the rate of positive lesions on capsule endoscopy (r=-0.342, P=0.001). Among the 39 patients with positive lesions on capsule endoscopy, the detection of Meckel's diverticulum was the highest (41%), followed by inflammatory bowel disease (21%).@*CONCLUSIONS@#Capsule endoscopy has a certain value in detecting small intestinal diseases, especially diseases in the jejunum and the ileum, in children with lower gastrointestinal hemorrhage.

A review of multimodal neuroimaging fusion methods and their clinical applications to brain diseases / 国际生物医学工程杂志

With the rapid development of neuroimaging technology and related data processing methods, multimodal neuroimaging has been widely used in research fields such as neuroscience and clinical diseases. In this paper, the current development of multimodal neuroimaging fusion algorithm and its application in the diagnosis and treatment of brain diseases were reviewed. The definitions, applications, and advantages of the three levels of multimodal neuroimaging fusion, i.e. early fusion, late fusion, and intermediate fusion, were introduced and analyzed. The commonly used multi-modal neuroimaging algorithm basing on signal source separation method and deep multi-modal learning was introduced. The application of multimodal neuroimaging technology in the diagnosis and treatment of severe brain diseases such as schizophrenia and Alzheimer's disease was further discussed. Finally, the existing challenges and future research directions of multimodal neuroimaging methods and applications were summarized.

Effect of mood stabilizer on gray matter volume in patients with bipolar disorder Ⅰ / 中华行为医学与脑科学杂志

Objective To investigate the abnormal change of gray matter volume in patients with euthymic bipolar disorder Ⅰ (BD-Ⅰ),and to elucidate the relationship between the use of different mood stabilizers and brain structure variations.Methods Voxel-based morphometry (VBM) was used to analyze the volume of local gray matter in 35 patients with BD-Ⅰ and 30 healthy controls(HC).The patients were divided into BD-Ⅰ with lithium group and BD-Ⅰ with valproate group according to different mood stabilizers.The volume differences of gray matter of the three groups were compared by one-way ANOVA.Results Compared with HC,BD-Ⅰ patients showed significantly reduced gray matter volume in the medial frontal cortex (MNI (x,y,z):2,34,-18),orbital frontal cortex (MNI(x,y,z):-32,22,-4),frontal operculum (MNI(x,y,z):38,18,4) and insula cortex (MNI(x,y,z):-32,22,-4) (P＜0.05).There was no significant difference in thevolume of gray matter between BD-Ⅰ with lithium group and BD-Ⅰ with valproate group(P＞0.05).Conclusion Emotional disturbance in patients with BD-Ⅰ may be associated with reduced gray matter volume in the medial frontal cortex,orbital frontal cortex,frontal operculum and insula cortex.There are not significant difference about the effects of lithium carbonate and valproate on cerebral gray matter volume in patients with BD-Ⅰ.

Association of Persistent Minimal Residual Disease with Poor Outcomes of Patients with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation / 中华医学杂志(英文版)

Background@#Several studies have shown that detection of minimal residual disease (MRD) in acute myeloid leukemia (AML) is an independent prognostic factor. This study aimed to evaluate the significance of dynamic MRD pretransplantation on outcome of AML patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*Methods@#We retrospectively analyzed 145 consecutive AML patients undergoing allo-HSCT in complete remission status between June 2013 and June 2016. MRD was determined with multiparameter flow cytometry after the first and second courses of chemotherapy and pre-HSCT.@*Results@#In matched sibling donor transplantation (MSDT) settings, patients with positive MRD had higher cumulative incidence of relapse (CIR) than those without MRD after the first (32.3 ± 9.7% vs. 7.7 ± 3.1%, χ = 3.661, P = 0.055) or second course of chemotherapy (57.1 ± 3.6% vs. 12.5 ± 2.7%, χ = 8.759, P = 0.003) or pre-HSCT (50.0 ± 9.7% vs. 23.0 ± 3.2%, χ = 5.547, P = 0.019). In haploidentical SCT (haplo-SCT) settings, the MRD status at those timepoints had no significant impact on clinical outcomes. However, patients with persistent positive MRD from chemotherapy to pre-HSCT had higher CIR than those without persistent positive MRD both in MSDT and haplo-SCT settings. Patients with persistent positive MRD underwent MSDT had the highest relapse incidence, followed by those with persistent positive MRD underwent haplo-SCT, those without persistent MRD underwent haplo-SCT, and those without persistent MRD underwent MSDT (66.7 ± 9.2% vs. 38.5 ± 6.0% vs. 18.8 ± 8.7% vs. 12.0 ± 1.0%, χ = 20.763, P < 0.001). Multivariate analysis showed that persistent positive MRD before transplantation was associated with higher CIR (hazard ratio [HR] = 1.69, 95% confidence interval [CI]: 1.200-2.382, P = 0.003), worse leukemia-free survival (HR = 1.812, 95% CI: 1.168-2.812, P = 0.008), and overall survival (HR = 2.354, 95% CI: 1.528-3.627, P < 0.001).@*Conclusion@#Our results suggest that persistent positive MRD before transplantation, rather than positive MRD at single timepoint, could predict poor outcome both in MSDT and haplo-SCT settings.

Progress on treatment of uveal melanoma / 国际眼科杂志(Guoji Yanke Zazhi)

@#Uveal melanoma(UM)is the most common primary intraocular malignant tumor of adult. The traditional treatment is enucleation, but it cannot completely avoid metastasis, and on the contrary, it stimulates to distant metastasis of tumor cells to some extent. According to the statistic of latest 30a, survival rates of UM patients with metastasis is still very low. Recently, many researches devoted to targeted therapy, immune therapy and radiotherapy, which have achieved gratifying results. We summarized these relative researches in this paper.

Comparative analysis on industrial standardization degree of Chinese and Korean ginseng / 中国中药杂志

Panax ginseng is a well-known medicinal plant all over the world. It has high nutritional value and medicinal value. China and South Korea are the major countries in the world for ginseng cultivation, production and exportation. China's ginseng production accounts for more than half of the world, but the output value is less than that of Korea. The standardization process of ginseng industry plays an important role. This paper makes a detailed analysis of the Chinese and Korean ginseng national standards and the standardization process, and makes a detailed comparative analysis of the categories, standard contents, index selection, age, implementation and promotion status of the Chinese and Korean ginseng standards. The development disadvantages of ginseng industry standardization were displayed. And we give our advises on the standard revision, implementation of China's ginseng industry standardization, hoping to enhance the competitiveness of China's ginseng industry.

Therapeutical effect of Allicin for colitis mice induced by DSS and its possible mechanisms / 中国免疫学杂志

Objective:To analyze the therapeutical effect of Allicin for colitis mice induced by DSS and its possible mechanisms. Methods:A total of 24 male mice were randomly divided into Control group,DSS group(2. 5% DSS,7 days) and Allicin group [DSS treatment and Allicin,10 mg/(kg·d),7 d]. Disease activity index,inflammatory score,TUNEL and Western bolt were performed to analyze the effect of Allicin on colitis induced by DSS. Results: With DSS group, the Allicin group had lower disease activity score and inflammatory score(P<0. 05). Allicin group had a lower number of intestinal epithelial cell apoptosis than that of DSS group,the difference was statistically significant(P<0. 05). Western bolt analysis shown that Allicin treatment significantly depressed the expression of p-JAK2 and p-STAT3 in intestinal mucosa when compared with these of DSS group ( P<0. 05 ) . Conclusion:Conclusion Allicin has significantly therapeutic effect on mice colitis induced by DSS, the possible mechanisms including anti-inflammatory effects,protected of the intestinal epithelial cells and inhibition of the JAK2/STAT3 signaling pathways.

CT imaging features for 2 cases of retroperitoneal solitary fibrous tumor / 中南大学学报(医学版)

OBJECTIVE@#To determine the CT imaging features for retroperitoneal solitary fibrous tumor (SFT).
@*METHODS@#The imaging features of CT for 2 SFT cases, confirmed by pathological examination, were retrospectively analyzed and compared with pathological results.
@*RESULTS@#The results of CT showed that retroperitoneal SFTs were large, well-defined and consisted of solid components with different density (equal or low). In the scan of contrast enhancement, tumors were strongly enhanced, and the multiple vascular shadows were seen in the tumor at arterial phase. There was progressive enhancement from the arterial to venous phase, and capsule of tumor was displayed. Histologically, the tumors were composed of spindle cells within a background of collagen stroma, and showed a wide range of growth patterns, alternating hypercellular (tumor cell-rich) and hypocellular (collagen-rich) areas. The diagnosis was confirmed by positive immunohistochemical staining for CD34 and bcl-2.
@*CONCLUSION@#The retroperitoneal SFT possesses a definite characteristic in CT imaging features, and the diagnosis can be confirmed by histopathology and immunohistochemistry.