[Materia medica illustrations related to the regional names in Shandong province in Ben Cao Tu Jing].

Ben Cao Tu Jing had 48 materia medica illustrations related to the regional names in Shandong province. It was found that 42 of them were plant medicinal materials, distributed in seven areas in Shandong province. This study examined these illustration of plant medicinal materials and found that 26 species of these illustration of plant medicinal materials were identified with three genera and 11 illustrations were unverified. Most materia medica illustrations relating to the regional names in Shandong province were found mainly in Yanzhou, Qizhou and Zizhou. This indicated that materia medica were widely used in these areas in the Northern Song Dynasty. The haustorium of Cuscuta Chinensis were depicted in the "Shanzhou Tu Si Zi" and the habitat of wild poriacocos was described. This showed that the illustrators of Ben Cao Tu Jing might have conducted fieldwork and reflected on the main principles about how to identify materia medica in Ben Cao Tu Jing Zou Chi. Inconsistencies were found between the illustrations and the expressions of plant medicinal materials in some illustrations, such as Gui Jiu, Ginsen and Shan Zhu Yu. This suggested that in the Northern Song Dynasty Stemmacantha Uniflora, Belamcanda chinensis might have been mixed up with Dysosma and Pinellia Pedatisecta might have been mixed up with Pinellia Ternata. This was in line with the compiling theories of Su Song that they could be recorded together when the illustrations and literature were inconsistent with each other.

[Comparison of the efficacy of IA and HAD induction regimens in the treatment of patients with newly diagnosed acute myeloid leukemia: a single-center study].

Objective: To compare the efficacy of two induction regimens, namely, idarubicin combined with cytarabine (IA) versus the combination of homoharringtonine, daunorubicin, and cytarabine (HAD) , in adult patients with newly diagnosed de novo acute myeloid leukemia (AML) . Methods: From May 2014 to November 2019, 199 patients diagnosed with AML receiving either the IA or HAD regimens were assessed for overall survival (OS) , relapse-free survival (RFS) , as well as the CR rate and the MRD negative rate after induction therapy. The differences in prognosis between the two induction therapy groups was assessed according to factors, including age, white blood cell (WBC) count, NPM1 mutation, FLT3-ITD mutation, 2017 ELN risk stratification, CR(1) transplantation, and the use of high-dose cytarabine during consolidation therapy, etc. Results: Among the 199 patients, there were 104 males and 95 females, with a median age of 37 (15-61) years. Ninety patients received the IA regimen, and 109 received the HAD regimen. Comparing the efficacy of the IA and HAD regimens, the CR rates after the first induction therapy were 71.1% and 63.3%, respectively (P=0.245) , and the MRD negative rates after the first induction therapy were 53.3% and 48.6%, respectively (P=0.509) . One patient in the IA group and two in the HAD group died within 60 days after induction. The two-year OS was 61.5% and 70.6%, respectively (P=0.835) , and the two-year RFS was 51.6% and 57.8%, respectively (P=0.291) . There were no statistically significant differences between the two groups. Multivariate analysis showed that the ELN risk stratification was an independent risk factor in both induction groups; CR(1) HSCT was an independent prognostic factor for OS and RFS in the IA patients and for RFS in the HAD patients but not for OS in the HAD patients. Age, WBC level, NPM1 mutation, and FLT3-ITD mutation had no independent prognostic significance. Conclusion: The IA and HAD regimens were both effective induction regimens for AML patients.

[Efficacy and safety of IAC regimen for relapse/refractory acute myeloid leukemia: a prospective randomized controlled study].

Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.

[Dasatinib combined with multi-agent chemotherapy regimen in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a prospective study from a single center].

Objective: This study evaluates the efficacy and safety of dasatinib combined with a multi-agent chemotherapy regimen of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) patients. Methods: This prospective, single-arm, and open clinical study enrolled 30 adult Ph(+) ALL patients who were newly diagnosed and treated from January 2016 to April 2018 in the center of this study. Standard induction chemotherapy was given for 4 weeks. However, dasatinib (100 mg/d) was continuously administered from day 8 until the end of the whole therapy in the induction therapy. Patients who are available for allogeneic or autologous stem cell transplantation (SCT) received transplantation when the disease was evaluated as complete remission. Results: All 30 patients achieved hematological complete remission (HCR) after the induction chemotherapy, and 70.0% (21/30) of them achieved the accumulated molecular complete remission (MCR) . The patients were followed up with a median follow-up time of 37.8 months (32.0-46.6) . The 3 year overall survival (OS) and 3 year hematological relapse-free survival (HRFS) were 68.1% and 61.6%, respectively. Moreover, 63.3% and 43.3% of the patients achieved molecular major remission and MCR, respectively. Consequently, 60.0% of the patients achieved MCR until 6 months. The patients who achieved MCR within 6 months had superior OS (P=0.004) , HRFS (P=0.049) , and event-free survival (EFS; P=0.001) . Fifteen patients (50.0%) received SCT at the first HCR. However, HRFS (P=0.030) and EFS (P=0.010) in the SCT group were better than those in the chemotherapy group. Conclusions: The regimen of dasatinib combined with a multi-agent chemotherapy was proven safe and effective in the treatment of newly diagnosed adult Ph(+) ALL patients. Clinical trial registration: ClinicalTrials.gov, NCT02523976.

[Effect of genetic polymorphism of TPMT and NUDT15 on the tolerance of 6-mercaptopurine therapy in adult acute lymphoblastic leukemia].

Objective: To investigate the effect of genetic polymorphisms of TPMT*2 rs1800462, TPMT*3B rs1800460, TPMT*3C rs1142345, and NUDT15 rs116855232 on the tolerance of 6-mercaptopurine (6-MP) therapy in adult acute lymphoblastic leukemia (ALL) . Methods: A total of 216 adult patients who were diagnosed with ALL and treated with cyclophosphamide, cytarabine, and 6-MP [complementary and alternative medicine (CAM) regimen] from September 2015 to December 2019 were included. Polymorphisms were detected by TaqMan SNP Genotyping Assay. Combined with clinical data, the influence of genetic polymorphism on the tolerance of 6-MP in the treatment of ALL was analyzed. Results: Among the 216 patients, 185 (85.65%) patients had B-ALL and 31 (14.35%) patients had T-ALL. 216 (100%) patients had CC genotype for both TPMT*2 rs1800462 and TPMT*3B rs1800460. The number of TT and TC genotypes for TPMT*3C rs1142345 was 209 (96.76%) and 7 (3.24%) , respectively. The allele frequency was 1.62% for TPMT*3C rs1142345. The number of CC, CT, and TT genotypes for NUDT15 rs116855232 was 166 (76.85%) , 48 (22.22%) , and 2 (0.93%) , respectively. The allele frequency was 12.04% for NUDT15 rs116855232. The TPMT*3C rs1142345 mutant group (TC+CC genotype) had less transfusion volume of packed red blood cell than the wild group (CC genotype) (P=0.036) , and the mutant group (TC+CC genotype) had a higher risk to develop hepatotoxicity (increased aspartate aminotransferase) than the wild group (CC genotype) (OR=9.559, 95% CI 1.135-80.475, P=0.038) . The durations of white blood cells (WBC) <1×10(9)/L and absolute neutrophil count (ANC) <0.5×10(9)/L in the NUDT15 rs116855232 mutation group (CT+TT genotype) were longer than that in the wild group (CC genotype) (P=0.005, P=0.007) , and the transfusion volume of apheresis-derived platelets in the mutant group (CT+TT type) was greater than that in the wild group (CC genotype) (P=0.014) . Conclusion: Genetic polymorphism of TMPT and NUDT15 has an effect on the tolerance of 6-MP in the treatment of adult ALL. Detecting genotypes of patients with ALL before treatment helps to optimize the dosage of 6-MP, which may help shorten the bone marrow suppression duration and reduce blood transfusion volume.

Lnc-RNA BLACAT1 regulates differentiation of bone marrow stromal stem cells by targeting miR-142-5p in osteoarthritis.

OBJECTIVE: Osteogenic differentiation of bone marrow stromal stem cells (BMSCs) is beneficial to the treatment of osteoarthritis (OA). Lnc-RNA BLACAT1 involves in occurrence and development of various diseases. However, the role of Lnc-RNA BLACAT1 in BMSCs differentiation under inflammation remains unclear. MATERIALS AND METHODS: Rat BMSCs were isolated and randomly divided into control group and inflammation group (addition of IL-6). The inflammation group was further divided into BLACAT1 siRNA group and BLACAT1 siRNA+miR-142-5p inhibitor group, followed by analysis of Lnc-RNA BLACAT1 expression by real time PCR, BMSCs proliferation, Caspase 3 activity, ALP activity, expression of Runx2, OC and PPARγ2 by real time PCR, and secretion of TNF-α and IL-1ß by enzyme-linked immunosorbent assay (ELISA). The bioinformatics software and the Luciferase reporter system analyze the targeted relationship between BLACAT1 and miR-142-5p. RESULTS: In inflammation group, Lnc-BLACAT1 expression was increased, along with inhibited BMSCs proliferation, increased Caspase 3 activity, decreased ALP activity, and expression of Runx2 and OC, increased PPARγ2 expression and secretion of TNF-α and IL-1ß. The difference was statistically significant compared with control group (p<0.05). MiR-142-5p is the target miRNA of Lnc-RNA BLACAT1. BLACAT1 siRNA down-regulated BLACAT1 expression, promoted cell proliferation, inhibited Caspase 3 activity, increased ALP activity and Runx2 and OC expression, decreased PPARγ2 expression and TNF-α and IL-1ß secretion. Compared with inflammation group, the difference was statistically significant (p<0.05). Of note, BLACAT1 siRNA+miR-142-5p inhibitor group reversed the effect of siRNA-mediated knockdown of BLACAT1. CONCLUSIONS: Lnc-RNA BLACAT1 expression was increased in inflammatory BMSCs, and knockdown of BLACAT1 promoted proliferation and osteogenic differentiation of BMSCs targeting miR-142-5p.

MiRNA-20a-5p accelerates the proliferation and invasion of non-small cell lung cancer by targeting and downregulating KLF9.

OBJECTIVE: To uncover the role of microRNA-20a-5p (miRNA-20a-5p) in the progression of Non-small cell lung cancer (NSCLC) and the underlying mechanism. PATIENTS AND METHODS: MiRNA-20a-5p level in NSCLC tissues and cell lines was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Its level in NSCLC patients with larger or smaller tumor size, and either with lymphatic metastasis or not was examined as well. Regulatory effects of miRNA-20a-5p on viability, cell cycle, and invasiveness of A549 and PC9 cells were assessed. The interaction between miRNA-20a-5p and KLF9 was explored by Dual-Luciferase Reporter Gene Assay and Spearman correlation test. At last, the role of miRNA-20a-5p/KLF9 axis in influencing the progression of NSCLC was determined. RESULTS: MiRNA-20a-5p was upregulated in NSCLC tissues and cell lines. Its level was much pronounced in NSCLC patients with larger tumor size or accompanied with lymphatic metastasis. Overexpression of miRNA-20a-5p in A549 cells enhanced viability, cell ratio in S phase, and invasiveness, while the knockdown of miRNA-20a-5p in PC9 cells achieved the opposite trends. KLF9 was confirmed to be the direct target of miRNA-20a-5p. There was a negative correlation between the expression levels of miRNA-20a-5p and KLF9 in NSCLC tissues. In addition, KLF9 overexpression could reverse the promotive effects of upregulated miRNA-20a-5p on the proliferation and invasiveness of A549 cells. On the contrary, the knockdown of KLF9 reversed the inhibitory effects of downregulated miRNA-20a-5p on cellular behaviors of PC9 cells. CONCLUSIONS: MiRNA-20a-5p stimulates NSCLC to proliferate and invade by targeting KLF9.

[Factors influencing the quality of Peucedanum Praeruptorum Dunn and "assessment of quality based on its features"].

The factors influencing the evaluation of the quality of Peucedanum praeruptorum Dunn, called "Qianhu" in Chinese, include the botanical origin, places of production, harvesting time and its nature of "Ci Xiong" (bolting and unbolting) etc. The orthodox products are derived from Peucedanum praeruptorum Dunn in successive dynasties, especially the unbolting one produced in Anhui and Zhejiang Provinces picked up during the Beginning of Winter. The "assessment of quality based on its features" includes the "Earthworm head" , "black skin of the root" , "gold inlaid with white jade" , "soft texture like sweet rice" and "strong fragrant smell" . Therefore, the "assessment of quality based on its features" is the summary of all its properties, including the morphology, color, flavor, and property, and it's also the background for evaluating its quality and embodying the wisdom of distinguishing experiences of ancient herbologists.

[Spectrum of somatic mutations and their prognostic significance in adult patients with B cell acute lymphoblastic leukemia].

Objective: To investigate the spectrum of gene mutations in adult patients with B-acute lymphoblastic leukemia (B-ALL), and to analyze the influences of different gene mutations on prognosis. Methods: DNA samples from 113 adult B-ALL patients who administered from June 2009 to September 2015 were collected. Target-specific next generation sequencing (NGS) approach was used to analyze the mutations of 112 genes (focused on the specific mutational hotspots) and all putative mutations were compared against multiple databases to calculate the frequency spectrum. The impact of gene mutation on the patients' overall survival (OS) and recurrence free survival (RFS) was analyzed by the putative mutations through Kaplan-Meier, and Cox regression methods. Results: Of the 113 patients, 103 (92.0%) harbored at least one mutation and 29 (25.6%) harbored more than 3 genes mutation. The five most frequently mutated genes in B-ALL are SF1, FAT1, MPL, PTPN11 and NRAS. Gene mutations are different between Ph+ B-ALL and Ph- B-ALL patients. Ph- B-ALL patients with JAK-STAT signal pathway related gene mutation, such as JAK1/JAK2 mutation showed a poor prognosis compared to the patients without mutation (OS: P=0.011, 0.001; RFS: P=0.014,<0.001). Patients with PTPN11 mutation showed better survival than those without mutation, but the difference was not statistically significant (P value > 0.05). Besides, in Ph+ B-ALL patients whose epigenetic modifications related signaling pathway genes were affected, they had a worse prognosis (OS: P=0.038; RFS: P=0.047). Conclusion: Gene mutations are common in adult ALL patients, a variety of signaling pathways are involved. The frequency and spectrum are varied in different types of B-ALL. JAK family gene mutation usually indicates poor prognosis. The co-occurrence of somatic mutations in adult B-ALL patients indicate the genetic complex and instability of adult B-ALL patients.

[Screening of adult Ph-like acute lymphoblastic leukemia by multiplex real-time quantitative PCR].

Objective: To investigate the feasibility of multiplex real-time RT-PCR with fluorescent probes in early screening of Ph-like acute lymphoblastic leukemia (ALL) and analyze the clinical feature and prognos. Method: A total of 118 adult B-ALL patients diagnosed between October 2010 and March 2016 were enrolled in this study. Multiplex RT-PCR was used to detect the Ph-like ALL related fusion gene and CRLF2 expression in 58 BCR-ABL and MLL rearrangement negative patients. The clinical features, treatment response and prognosis were analyzed in Ph-like fusion gene positive and/or CRLF2 over-expression patients. Result: Among 58 patients, 9 patients (9/58, 15.5%) showed Ph-like ALL related fusion genes positive and 10 patients (10/58, 17.2%) showed CRLF2 over-expression. There were statistical differences in age, WBC count, immunophenotypes, cytogenetics and risk stratification among Ph-like fusion gene positive or CRLF2 over-expression patients, Ph(+) patients, MLL(+) patients and B-other patients. The 2-year overall survival rates were 65%, 47%, 64% and 74% respectively among these four groups (P=0.043) . The 2-year relapse free survival rates were 51%, 39%, 62% and 70% respectively among these four groups (P=0.010) . Conclusion: Routine screening of Ph-like ALL by multiplex RTPCR is feasible.

One novel and two recurrent mutations in the keratin 5 gene identified in Chinese patients with epidermolysis bullosa simplex.

Epidermolysis bullosa simplex (EBS) is a group of inherited skin diseases, characterized by the formation of intraepidermal blisters. We performed genetic analysis of the keratin 5 (KRT5) gene in two Chinese pedigrees. One novel missense mutation was identified in a patient with sporadic EBS (general, non-Dowling-Meara). Sequence analysis showed a heterozygous T > A transition at nucleotide 1730 of KRT5, changing phenylalanine (Phe) to tyrosine (Tyr) at position 577 of the keratin 5 (K5). In addition, two recurrent mutations c.1649delG (p.Gly550AlafsX77) and c.508G > (p.Glu170Lys) in KRT5 were identified in Chinese patients with mottled pigmentation EBS and localized EBS, respectively. None of the mutations were found in any unaffected family members or in an additional 100 unrelated control samples. These results suggest that these mutations are pathogenic and might be one of the potential causes of EBS in these Chinese patients.

A novel frameshift mutation of the EDA1 gene in a Chinese Han family with X-linked hypohidrotic ectodermal dysplasia.

Hypohidrotic ectodermal dysplasia (HED) is a rare skin disease characterized by hypotrichosis, hypodontia and hypohidrosis. HED can be autosomal dominant, autosomal recessive or X-linked. However, X-linked HED (XLHED; OMIM 305100) is the most common form. Mutations within the EDA1 gene, which encodes ectodysplasin-A, are responsible for XLHED. In this study, we investigated the EDA1 gene in a Chinese Han family with XLHED, and found a novel 1-bp deletion mutation (c.952delG) in exon 9 of the EDA1 gene, which results in a frameshift and premature termination codon. This result suggests that the c.952delG mutation of the EDA1 gene is likely to be the disease-causing mutation for XLHED in this family. Our study adds new data to the worldwide knowledge of the molecular basis of XLHED.

Local changes in aluminium, calcium and phosphorus content of bone caused by alumina implant.

Thirty rabbits were divided equally into 5 groups randomly. A hole, 6 mm in diameter and 2 mm deep, was bored on each iliac crest. Two pieces of alumina were implanted into the hole of one side, while the opposite side served as control. These rabbits were killed on 10, 20, 40, 60 and 90 days after operation. Calcium, phosphorus and aluminium contents of iliac bone on both sides were determined by Inductively Coupled Plasma--Atomic Emission Spectrometry. The results showed that the aluminium content of the implanted side in each group was higher than that of the control and difference was significant in 10, 40 and 60 day groups (P < 0.05). This shows that the implant releases aluminium into the bone. Moreover, the calcium and phosphorus contents were significantly lower on the implanted side than on the control side in 10 and 20 day groups (P < 0.05-0.001). Apparently, the aluminium released from the implant in the early stage can interfere with the local calcium and phosphorus metabolism and delay the mineralization of the bone.