Prognostic Significance of LPCAT1 in Adult Acute Myeloid Leukemia Patients with FAB Subtype M2 / 中国实验血液学杂志

OBJECTIVE@#To study the prognostic value of LPCAT1 in acute myeloid leukemia (AML).@*METHODS@#TaqMan-based reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect relative expression of LPCAT1 in 214 newly diagnosed adult AML patients and 24 normal controls. Survival functions were estimated using the Kaplan-Meier method and were compared by the Log-rank test. A Cox proportional hazard regression model was used to identify prognostic factors.@*RESULTS@#The expression level of LPCAT1 in adult AML was 34.37%(1.83%-392.63%), which was significantly lower than 92.81%(2.60%-325.84%) of normal controls (P<0.001). The prognostic significance of LPCAT1 was evaluated in 171 non-acute promyelocytic leukemia patients with complete clinical information and prognostic data. Survival analysis showed that the expression level of LPCAT1 had no significant effect on the prognosis of the whole cohort. However, in AML patients with FAB subtype M2 (AML-M2), the 2-year relapse-free survival (RFS) rate of patients with low LPCAT1 expression was 35.4%(95%CI: 0.107-0.601), which was significantly lower than 79.2%(95%CI: 0.627-0.957) of patients with high LPCAT1 expression (P=0.012). Multivariate analysis showed that low expression of LPCAT1 was an independent risk factor for RFS of AML-M2 patients (HR=0.355, 95%CI: 0.126-0.966, P=0.049).@*CONCLUSION@#In adult AML patients LPCAT1 shows low expression. Low LPCAT1 expression is an independent risk factor for RFS in M2-AML patients.

Maackiain inhibits proliferation and promotes apoptosis of nasopharyngeal carcinoma cells by inhibiting the MAPK/Ras signaling pathway / 中国天然药物

Nasopharyngeal carcinoma (NPC) is the third most common malignancy with a high recurrence and metastasis rate in South China. Natural compounds extracted from traditional Chinese herbal medicines have been developed and utilized for the treatment of a variety of cancers with modest properties and slight side effects. Maackiain (MA) is a type of flavonoid that was first isolated from leguminous plants, and it has been reported to relieve various nervous system disorders and exert anti-allergic as well as anti-inflammatory effects. In this study, we demonstrated that MA inhibited proliferation, arrested cell cycle and induced apoptosis in nasopharyngeal carcinoma CNE1 and CNE2 cells in vitro and in vivo. The expression of the related proteins associated with these processes were consistent with the above effects. Moreover, transcriptome sequencing and subsequent Western blot experiments revealed that inhibition of the MAPK/Ras pathway may be responsible to the anti-tumor effect of MA on NPC cells. Therefore, the effects of MA and an activator of this pathway, tertiary butylhydroquinone (TBHQ), alone or combination, were investigated. The results showed TBHQ neutralized the inhibitory effects of MA. These data suggest that MA exerts its anti-tumor effect by inhibiting the MAPK/Ras signaling pathway and it has the potential to become a treatment for patients with NPC.

Comparison of safety and effectiveness of active migration technique and in situ lithotripsy technique in the treatment of 1-2 cm upper ureteral calculi by flexible ure-teroscopy / 北京大学学报(医学版)

OBJECTIVE@#To compare the safety and effectiveness of active migration technique and in situ lithotripsy technique in the treatment of 1-2 cm upper ureteral calculi by retrograde flexible ureteroscopy.@*METHODS@#A total of 90 patients with 1-2 cm upper ureteral calculi treated in the urology department of Beijing Friendship Hospital from August 2018 to August 2020 were selected as the subjects. The patients were divided into two groups using random number table: 45 patients in group A were treated with in situ lithotripsy and 45 patients in group B were treated with active migration technique. The active migration technique was to reposition the stones in the renal calyces convenient for lithotripsy with the help of body position change, water flow scouring, laser impact or basket displacement, and then conduct laser lithotripsy and stone extraction. The data of the patients before and after operation were collected and statistically analyzed.@*RESULTS@#The age of the patients in group A was (51.6±14.1) years, including 34 males and 11 females. The stone diameter was (1.48±0.24) cm, and the stone density was (897.8±175.9) Hu. The stones were located on the left in 26 cases and on the right in 19 cases. There were 8 cases with no hydronephrosis, 20 cases with grade Ⅰ hydronephrosis, 11 cases with grade Ⅱ hydronephrosis, and 6 cases with grade Ⅲ hydronephrosis. The age of the patients in group B was (51.8±13.7) years, including 30 males and 15 females. The stone diameter was (1.52±0.22) cm, and the stone density was (964.6±214.2) Hu. The stones were located on the left in 22 cases and on the right in 23 cases. There were 10 cases with no hydronephrosis, 23 cases with grade Ⅰ hydronephrosis, 8 cases with grade Ⅱ hydronephrosis, and 4 cases with grade Ⅲ hydronephrosis. There was no significant diffe-rence in general parameters and stone indexes between the two groups. The operation time of group A was (67.1±16.9) min and the lithotripsy time was (38.0±13.2) min. The operation time of group B was (72.2±14.8) min and the lithotripsy time was (40.6±12.6) min. There was no significant difference between the two groups. Four weeks after operation, the stone-free rate in group A was 86.7%, and in group B was 97.8%. There was no significant difference between the two groups. In terms of complications, 25 cases of hematuria, 16 cases of pain, 10 cases of bladder spasm and 4 cases of mild fever occurred in group A. There were 22 cases of hematuria, 13 cases of pain, 12 cases of bladder spasm and 2 cases of mild fever in group B. There was no significant difference between the two groups.@*CONCLUSION@#Active migration technique is safe and effective in the treatment of 1-2 cm upper ureteral calculi.

Clinical Features and Prognosis of Multiple Myeloma Patients with Secondary Primary Malignancies / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical characteristics and prognosis of multiple myeloma(MM) patients with secondary primary malignancies.@*METHODS@#The clinical data of newly diagnosed MM patients admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to December 2019 were retrospectively analyzed. The patients with secondary primary malignancies were retrieved, and their clinical features and prognosis were evaluated.@*RESULTS@#A total of 1 935 patients with newly diagnosed MM were admitted in this period, with a median age of 62 (18-94) years old, of which 1 049 cases were hospitalized twice or more. There were eleven cases with secondary primary malignancies (the incidence rate was 1.05%), including three cases of hematological malignancies (2 cases of acute myelomonocytic leukemia and 1 case of acute promyelocytic leukemia) and eight cases of solid tumors (2 cases of lung adenocarcinoma, and 1 case each of endometrial cancer, esophageal squamous cell carcinoma, primary liver cancer, bladder cancer, cervical squamous cell carcinoma, and meningioma). The median age of onset was 57 years old. The median time between diagnosis of secondary primary malignancies and diagnosis of MM was 39.4 months. There were seven cases with primary or secondary plasma cell leukemia, the incidence rate was 0.67%, and the median age of onset was 52 years old. Compared with the randomized control group, the β2-microglobulin level in the secondary primary malignancies group was lower (P=0.028), and more patients were in stage I/II of ISS (P=0.029). Among the 11 patients with secondary primary malignancies, one survived, ten died, and the median survival time was 40 months. The median survival time of MM patients after the secondary primary malignancies was only seven months. All seven patients with primary or secondary plasma cell leukemia died, with a median survival time of 14 months. The median overall survival time of MM patients with secondary primary malignancies was longer than that of the patients with plasma cell leukemia (P=0.027).@*CONCLUSION@#The incidence rate of MM with secondary primary malignancies is 1.05%. MM patients with secondary primary malignancies have poor prognosis and short median survival time, but the median survival time is longer than that of patients with plasma cell leukemia.

TCM understanding and treatment strategy of hypertension complicated with sexual dysfunction / 中国中药杂志

Hypertension and its target organ damage have become a major public health problem. Sexual dysfunction is a new problem in the treatment of modern hypertension. Modern pathophysiological studies have shown that hypertension can lead to sexual dysfunction. In addition, three major hypotensive drugs represented by diuretics can also lead to sexual dysfunction. In traditional Chinese medicine(TCM), hypertension belongs to "vertigo" "headache" "head wind", etc. In the past, the understanding of the TCM pathogenesis of hypertension was mainly from the perspectives of "liver wind" and "Yang hyperactivity". However, based on the in-depth research on ancient and modern literature and medical records and many years of clinical practice, it has been identified that kidney deficiency was the key pathogenesis. Hypertension complicated with sexual dysfunction belongs to the category of kidney deficiency syndrome in TCM, especially the deficiency of kidney Yin. Previous studies by other research groups showed that Yin-enriching and kidney-tonifying method could effectively reduce blood pressure, improve sexual dysfunction, reverse risk factors, and protect target organs. This article systematically discussed the TCM understanding, modern pathophysiological mechanism, and the clinical treatment strategy of kidney-tonifying drugs(single drugs and compounds) in the treatment of hypertension complicated with sexual dysfunction in order to provide a scientific basis for kidney-tonifying method in the treatment of hypertension complicated with sexual dysfunction.

Research ideas of core formulas-syndromes based on disease-syndrome-treatment combination / 中国中药杂志

The relationship between disease and syndrome is a research focus in integrated traditional Chinese and western medicine. Depending on the focus, the disease-syndrome combination for treatment is manifested as the different treatment methods for the same disease and the same treatment method for different diseases based on the syndrome, and different treatment methods for the same syndrome and the same treatment method for different syndromes based on the disease. The mainstream model is the combination of di-sease identification in modern medicine with syndrome identification and core pathogenesis in traditional Chinese medicine. However, current research on the combination of disease and syndrome and core pathogenesis tends to focus on the heterogeneity between disease and syndrome and the separation of syndrome and treatment. Therefore, the study proposed the research idea and model of core formulas-syndromes(CFS). According to the theory of formula-syndrome correspondence, the research idea of CFS deepens the research on core pathogenesis, which aims to summarize the core formulas and syndromes for diseases. The research fields include diagnostic criteria for the indications of formulas, distribution patterns of formulas and syndromes for diseases, the evolution of medicinal-syndrome based on formulas-syndromes, formula combination law based on formulas-syndromes, and the dynamic evolution of formulas-syndromes. Through the summary of ancient classics, clinical experience, and medical records, and with the methods of expert consultation, factor analysis, and clustering analysis, research on the diagnostic criteria for the indications of formulas aims to explore the diagnosis information such as the diseases, symptoms, signs, and pathophysiology. The research on the distribution patterns of formulas and syndromes for diseases tends to summarize the specific types of formulas and syndromes for the diseases through literature research and clinical cross-sectional studies based on the establishment of diagnostic criteria for the indications of formulas. The research on the evolution of medicinal-syndrome aims to clarify the medicinal-syndrome law through literature and clinical research. The formula combination law refers to the fact that the core prescriptions for a disease often appear in combination with other prescriptions on a regular basis. The dynamic evolution of formulas-syndromes refers to the continuous transformation and change of formulas and syndromes in the process of disease development with changes in time and space. The CFS is conducive to the unification of disease, syndrome and treatment and to the deepening of the research model of disease and syndrome integration.

Clinical application of Chaihu Jia Longgu Muli Decoction based on modern pathophysiology mechanism / 中国中药杂志

Chaihu Jia Longgu Muli Decoction was firstly recorded in Treatise on Cold Damage(ZHANG Zhong-jing, Eastern Han dynasty). According to this medical classic, it is originally used in the treatment of the Shaoyang and Yangming syndrome. Based on the modern pathophysiological mechanism, this study interpreted the classic provisions of Chaihu Jia Longgu Muli Decoction. Original records of "chest fullness" "annoyance" "shock" "difficult urination" "delirium" "heavy body and failing to turn over" all have profound pathophysiological basis, involving disorders in cardiovascular, respiratory, nervous, and mental systems. This formula is widely used, which can be applied to treat epilepsy, cerebral arteriosclerosis, cerebral infarction, and other cerebrovascular diseases, hypertension, arrhythmia, and other cardiovascular diseases, insomnia, constipation, anxiety, depression, cardiac neurosis and other acute and chronic diseases as well as diseases in psychosomatic medicine. The clinical indications include Bupleuri Radix-targeted syndrome such as fullness and discomfort in chest and hypochondrium, bitter taste mouth, dry throat, and dizziness, the insomnia, anxiety, depression, susceptibility to fright, upset, dreamfulness and other psychiatric symptoms, red tongue, thick and yellow tongue coating, and wiry hard and powerful pulse. This formula was found to be used in combination with other formulas, such as Gualou Xiebai Decoction, Wendan Decoction, Zhizhu Pills, Juzhijiang Decoction, Suanzaoren Decoction, and Banxia Baizhu Tianma Decoction.

Arrhythmia:innovative understanding from traditional Chinese medicine and treatment by classic herbal formulas / 中国中药杂志

Arrhythmia, a common and frequently occurring cardiovascular disease, causes a heavy burden on the public health of China. Approximately 20 million patients are suffering from this disease in China and treated by pharmacological and surgical therapies. However, antiarrhythmic drugs can cause arrhythmia and surgical treatment has the risks of failure and recurrence. Therefore, the clinical outcome of arrhythmia remains to be improved. According to the traditional Chinese medicine(TCM) theory, arrhythmia is a disease of palpitation induced by 7 conditions: liver depression and Qi stagnation, accumulation of turbid phlegm, fluid retention attacking the heart, fire-heat disturbing the heart, stasis obstruction of heart vessel, cold congealing in heart vessel, and the deficiency of Qi, blood, Yin, and Yang. Therefore, this study concisely proposed 7 TCM syndromes of arrhythmia, including the palpitation due to depression, phlegm, fluid retention, fire, blood stasis, cold, and deficiency. The corresponding treatment strategies were recommended as follows: Chaihu Longgu Muli Decoction for the palpitation due to depression, Wendan Decoction for the palpitation due to phlegm, Linggui Zhugan Decoction for the palpitation due to fluid retention, Sanhuang Xiexin Decoction for the palpitation due to fire, Xuefu Zhuyu Decoction for the palpitation due to blood stasis, and Mahuang Fuzi Xixin Decoction for the palpitation due to cold, and Guizhi Gancao Decoction, Guizhi Gancao Longgu Muli Decoction, Huanglian Ejiao Decoction, Zhigancao Decoction, and Guipi Decoction for the palpitation due to the deficiency of Qi, blood, Yin, and Yang. Multiple formulas should be combined if the patient presents several TCM syndromes simultaneously. According to the principles of the correspondence between formula and syndrome and the treatment with consideration to both pathogenesis and pathology and both herbal nature and pharmacology, this study proposed an integrated treatment model of "pathogenesis-pathology-nature-pharmacology" to enhance the clinical efficacy of classic herbal formulas in the treatment of arrhythmia.

Connotation of Xiao Chaihu Decoction combined with Maxing Shigan Decoction based on severe cases and modern pathophysiological mechanism and application for severe pulmonary infection and acute exacerbation of chronic obstructive pulmonary disease in critical care medicine / 中国中药杂志

Xiao Chaihu Decoction combined with Maxing Shigan Decoction is a classic herbal formula. All of them are derived from Treatise on Cold Damage(Shang Han Lun) by ZHANG Zhong-jing. This combination has the effects of harmonizing lesser yang, relieving exterior syndrome, clearing lung heat, and relieving panting. It is mainly used for treating the disease involving the triple-Yang combination of diseases and accumulation of pathogenic heat in the lung. Xiao Chaihu Decoction combined with Maxing Shigan Decoction is a classic combination for the treatment of exogenous diseases involving the triple-Yang combination. They are commonly used in exogenous diseases, especially in the north of China. This combination is also the main treatment strategy for coronavirus disease 2019(COVID-19) accompanied by fever and cough. Maxing Shigan Decoction is a classical herbal formula for treating the syndrome of phlegm-heat obstructing the lung. "Dyspnea after sweating" suggests the accumulation of pathogenic heat in the lung. Patients with mild symptoms may develop cough and asthma along with forehead sweating, and those in critical severe may develop whole-body sweating, especially the front chest. Modern medicine believes that the above situation is related to lung infection. "Mild fever" refers to syndromes rather than pathogenesis. It does not mean that the heat syndrome is not heavy, instead, it suggests that severe heat and inflammation have occurred. The indications of Xiao Chaihu Decoction combined with Maxing Shigan Decoction are as follows.(1) In terms of diseases, it is suitable for the treatment of viral pneumonia, bronchopneumonia, lobar pneumonia, mycoplasma pneumonia, COVID-19 infection, measles with pneumonia, severe acute respiratory syndrome(SARS), avian influenza, H1N1 influenza, chronic obstructive pulmonary disease with acute exacerbation, pertussis, and other influenza and pneumonia.(2) In terms of syndromes, it can be used for the syndromes of bitter mouth, dry pharynx, vertigo, loss of appetite, vexation, vomiting, and fullness and discomfort in the chest and hypochondrium. It can also be used to treat alternate attacks of chill and fever and different degrees of fever, as well as chest tightness, cough, asthma, expectoration, dry mouth, wanting cold drinks, feeling agitated, sweating, yellow urine, dry stool, red tongue, yellow or white fur, and floating, smooth, and powerful pulse, especially the right wrist pulse.

Zhenwu Decoction:connotation interpretation based on severe cases and modern pathophysiological mechanisms and application in treatment of heart failure in critical care unit / 中国中药杂志

Zhenwu Decoction is recorded in Treatise on Febrile Diseases by an outstanding physician ZHANG Zhong-jing in the Han dynasty. With effect of warming yang, transforming Qi, and promoting urination, Zhenwu Decoction is mainly used to treat edema due to yang deficiency. The studies of the severe and critical cases and the pathophysiological mechanisms have demonstrated that the record of Zhenwu Decoction in Treatise on Febrile Diseases describes the clinical symptoms and therapeutic regimen of acute heart failure. The syndrome treated by this formula may be related to the misdiagnosis and wrong treatment. Due to the difficult distinguishing between cardiogenic dyspnea and pulmonary dyspnea, high doses of Ephedrae Herba may be misused for inducing sweating, which may finally lead to the acute aggravation of heart failure, electrolyte disorder, and pulmonary infection. The syndrome treated by Zhenwu Decoction can illustrate the lack of experience of ancient physicians in treating acute heart failure. The description of "trembling and shivering" may be the clinical manifestation of heart failure, which is an upgraded version of "trembling and shaking" treated by Linggui Zhugan Decoction.(1)In terms of diseases, Zhenwu Decoction is suitable for the treatment of acute or chronic heart failure, cardiorenal syndrome, and diuretic resistance. The decoction is especially suitable for treating whole heart failure, acute heart failure, heart failure with reduced ejection fraction, and heart failure with the syndrome of sold and dampness. In addition, it can be used to treat both type Ⅱ and type Ⅳ cardiorenal syndrome.(2)In terms of symptoms, Zhenwu Decoction can be used for treating chest tightness, palpitations, lower limb edema, difficult urination or increased urine output, fear of cold, pale fat tongue with teeth marks, white and slippery tongue fur, and deep or slow pulse.(3)In terms of the pharmacological mechanism, Zhenwu Decoction treats heart failure following the principle of promoting urination, expanding blood vessels, and invigorating heart in modern medicine. Aconiti Lateralis Radix Praparata is the sovereign herb in the formula, with the recommended dosage of 30-60 g. However, arrhythmia may be caused by high doses of Aconiti Lateralis Radix Praparata, which should be used with concern. In addition to Zhenwu Decoction, Shenqi Pills, Renshen Decoction, Wuling Powder, and Fangji Huangqi Decoction with the effect of invigorating spleen, replenishing Qi, warming Yang, and promoting urination can be used in the recovery stage. The therapy of reinforcing Yang was the last choice for critical cases due to the lack of medical conditions, unclear clinical diagnosis in history, which should be treated objectively now.

Connotation of distal bleeding based on modern pathophysiological mechanism and application of Huangtu Decoction for acute coronary syndrome complicated with acute upper gastrointestinal hemorrhage in critical care medicine / 中国中药杂志

Huangtu Decoction, first recorded in Essentials from the Golden Cabinet(Jin Kui Yao Lue) from ZHANG Zhong-jing in Han dynasty, is used to treat distal bleeding. It is mainly treated for the syndrome of failing to control blood with spleen-yang deficiency. The connotation of distal bleeding is more extensive, including not only upper gastrointestinal bleeding in the traditional sense such as peptic ulcer bleeding, gastrointestinal tumors, gastric mucosal lesions, vascular dysplasia, esophagogastric variceal bleeding, and pancreatic and biliary tract injury, but also other anorectal diseases such as part colon and rectal cancer swelling or polyps, hemorrhoids, and anal fissure and other parts of bleeding such as epistaxis, thrombocytopenia, functional uterine bleeding, threatened abortion, and unexplained hematuria. Distal bleeding also involves syndromes of failing to keep part deficient and cold fluids in interior, such as nocturia, enuresis, clear nose, sweating, cold tears, and leucorrhea, and excessive gastrointestinal bleeding caused by anti-plate and anticoagulant drugs, unexplained positive in the fecal occult blood test, and other modern clinical new problems. The indications of Huangtu Decoction include not only lower blood, defecation before blood, distant blood, hematemesis, epistaxis, and other diseases in traditional Chinese medicine, but also three types of clinical manifestations including bleeding, deficiency syndrome, and stagnant heat syndrome. In the clinic, Huangtu Decoction can be used to treat acute upper gastrointestinal bleeding, acute coronary syndrome complicated with acute upper gastrointestinal bleeding, bleeding events caused by excessive antiplatelet and anticoagulant drugs, unexplained positive in the fecal occult blood test, gastrointestinal tumor with bleeding, thrombocytopenia, and other acute and critical diseases. The dosage of Cooking Stove Earthkey, Rehmanniae Radix, and Asini Corii Colla in Huangtu Decoction is the key to hemostasis.

Connotation of Shenqi Pills based on severe cases in cardiovascular care unit and modern pathophysiological mechanism and application of Shenqi Pills for heart failure, renal failure, cardiorenal syndrome, and diuretic resistance in critical care medicine / 中国中药杂志

Shenqi Pills, first recorded in Essentials from the Golden Cabinet(Jin Kui Yao Lue) from ZHANG Zhong-jing in Han dynasty, have the effect of warming and tonifying the kidney Qi and are mainly used for the treatment of insufficiency of kidney Qi and kidney Yang. According to modern medicine, kidney Qi involves heart function, kidney function, immune function, and so on. The clinical indications of Shenqi Pills include kidney deficiency, abnormal fluid, and abnormal urination, and the last one is classified into little urine, much urine, and dysuria. In clinical settings, Shenqi Pills can be applied for the treatment of heart failure, renal failure, cardiorenal syndrome, and diuretic resistance, as well as endocrine, urological, orthopedic, and other chronic degenerative diseases. Shenqi Pills are ideal prescriptions for the weak constitution and emergency treatment. It is of great value and significance to carry out in-depth research on the connotation of the classic articles by integrating TCM and western medicine based on "pathogenesis combined with pathology and drug properties combined with pharmacology".

Interpretation of Expert Consensus on Diagnosis and Treatment of Hypertension with Traditional Chinese Medicine / 中国实验方剂学杂志

In the "major preventable diseases and health problems in China in the next 20 years" released by the Chinese Academy of Engineering， hypertension takes the second place. As a metabolic disease， hypertension has become a major global public health problem. In recent years， owing to the multiple targets， multiple components， and holistic regulation， traditional Chinese medicine （TCM） has attracted the interest of scholars in the treatment of hypertension. Especially for young patients and patients with early-onset hypertension， it is expected to achieve the purpose of stopping or reducing western medicine and decreasing adverse reactions by syndrome differentiation and treatment. Through literature review and expert consultation， the Society of Cardiovascular Diseases of China Association of Chinese Medicine has organized experts to formulate comprehensive intervention strategies of TCM for hypertension and finally developed the Expert Consensus on Diagnosis and Treatment of Hypertension with Traditional Chinese Medicine （hereinafter referred to as the Consensus）. It was demonstrated and approved at the annual meeting of the Society of Cardiovascular Diseases of China Association of Chinese Medicine in December 2018 and officially published in August 2019. Combined with literature research and clinical antihypertensive practice of TCM， this paper aims to make a detailed interpretation of the key pathogenesis， syndromes， classical prescriptions， and syndrome differentiation-based medication in the Consensus， which is expected to promote the clinical popularization and application of the Consensus. The conclusions are as follows. The pathogenesis of hypertension can be classified into fire syndrome， fluid-retention syndrome， and deficiency syndrome. In terms of syndrome characteristics， hypertension is mainly divided into three major syndromes： ascendant hyperactivity of liver Yang， stagnation of phlegm-fluid， and deficiency of kidney Yin. Moreover， it details the key points in the treatment of hypertension with the recommended classical prescriptions and the medication rules. As for the non-drug therapy， Taiji， Baduanjin， Qigong， yoga， acupuncture， moxibustion， massage， pricking collaterals， cupping， and foot bathing are also recommended to relieve clinical symptoms and control blood pressure. In terms of health care， it is emphasized to pay attention to "uncontrollable factors of blood pressure" such as exogenous factors， emotional disorders， insomnia， and constipation.

Gene Mutation and Overexpression of Newly Diagnosed Multiple Myeloma Patients / 中国实验血液学杂志

OBJECTIVE@#To analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients.@*METHODS@#Bone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH).@*RESULTS@#Gene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression.@*CONCLUSION@#There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.

Discovery of a small-molecule inhibitor of carbamoyl phosphate synthase 1 and its anti-colorectal cancer mechanism / 药学学报

The carbamoyl phosphate synthase 1 (CPS1) enzyme is involved in the first phase of the urea cycle, providing a prerequisite molecule for pyrimidine synthesis, as well as promoting tumor cell proliferation and growth. Studies have found that CPS1 is highly expressed in a variety of tumors, including colorectal cancer, lung cancer, etc. and its overexpression is related to the poor prognosis of tumors. Thus, small molecules targeted to inhibit the function of CPS1 in tumors may provide therapeutic benefits for cancer patients who overexpress CPS1. In this study, the function of CPS1 was investigated in vitro, and we found that overexpression of CPS1 can enhance the migration ability of colorectal cancer cells HCT15. Here, based upon the existing crystal structure, combined with high-throughput virtual screening, we obtained 8 candidate small molecule compounds. In vitro activity evaluation, we found that compound 3 has good anti-HCT15, HCT116 cell proliferation activity (HCT15, IC50, 7.69 ± 1.10 μmol‧L-1, HCT116, IC50, 13.53 ± 0.46 μmol‧L-1). Subsequently, molecular docking and molecular dynamics (MD) simulation analysis showed that, compound 3 could target and inhibit the activity of CPS1. In vitro studies showed that compound 3 could inhibit the migration of HCT15 cells, as well as induced cell cycle arrest and apoptosis. Taken together, this study found that compound 3 is a potential small molecule inhibitor that targets CPS1, which provides the experimental basis and theoretical basis for the development of targeted intervention small molecule therapeutic drugs. Based upon the chemical structure of compound 3, we will shed new light on further optimizing its activity and therapeutic potential, which may provide a therapeutic benefit to the patients with CPS1-related tumors.

Sleep-improving mechanism of Chaiqin Ningshen Granules in insomnia rats: based on hippocampal metabonomics / 中国中药杂志

With the ultra high performance liquid chromatography-quadruple-electrostatic field orbitrap high resolution mass spectrometry(UHPLC-Q Exactive Orbitrap-MS)-based metabonomics technology, this study aims to analyze the effect of Chaiqin Ningshen Granules(CNG) on endogenous metabolites in insomnia rats of liver depression syndrome and explore the sleep-improving mechanism of this prescription. Parachlorophenylalanine(PCPA, ip) and chronic stimulation were combined to induce insomnia of liver depression pattern in rats, and the effect of CNG on the macroscopic signs, hemorheology, and neurotransmitters in the hippocampus of insomnia rats of liver depression syndrome was observed. After the administration, rat hippocampus was collected for liquid chromatography-mass spectrometry(LC-MS) analysis of the metabolomics. Principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were employed for analyzing the metabolites in rat hippocampus and screening potential biomarkers. MetPA was used to yield the related metabolic pathways and metabolic networks. The results show that the drugs can significantly improve the mental state, liver depression, and blood stasis of rats, significantly increase the content of 5-hydroxytryptamine(5-HT) and gamma aminobutyric acid(GABA) in hippocampus(except low-dose CNG), and significantly reduce the content of glucose(Glu)(except low-dose CNG). Among them, estazolam and high-dose CNG had better effect than others. Metabolomics analysis yielded 27 potential biomarkers related to insomnia. MetPA analysis showed 4 metabolic pathways of estazolam in intervening insomnia and 3 metabolic pathways of high-dose CNG in intervening insomnia, involving purine metabolism, glycerophospholipid metabolism, histidine metabolism, and caffeine metabolism. CNG can alleviate insomnia by regulating endogenous differential metabolites and further related metabolic pathways. The result lays a basis for further elucidating the mechanism of CNG in improving sleep.

Effect of wheat-grain moxibustion on the expression of Beclin-1/GRP78 in spinal dorsal horn in rats with cervical spondylotic radiculopathy / 中国针灸

OBJECTIVE@#To observe the effect of wheat-grain moxibustion at "Dazhui" (GV 14) on the expressions of Beclin-1 and GRP78 in spinal dorsal horn in rats with cervical spondylotic radiculopathy (CSR), and to explore the possible analgesic mechanism of wheat-grain moxibustion for CSR.@*METHODS@#A total of 48 SD rats were randomly divided into a sham operation group, a model group, a wheat-grain moxibustion group and a wheat-grain moxibustion+3-MA group, 12 rats in each group. The CSR model was prepared by spinal cord insertion method. Three days after modeling, the rats in the model group were intraperitoneally injected with 1 mL of 0.9% sodium chloride solution; the rats in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14, 6 cones per time) on the basis of the model group; the rats in the wheat-grain moxibustion+3-MA group were intraperitoneally injected with 3-MA solution and wheat-grain moxibustion at "Dazhui" (GV 14, 6 cones per time). The three groups were intervened for 7 days, once a day. The gait score and mechanical pain threshold were observed before treatment and 7 days into treatment; after the treatment, the expressions of mRNA and protein of Beclin-1 in spinal dorsal horn were detected by real-time fluorescence quantitative PCR and immunohistochemistry; the expression of GRP78 protein in spinal dorsal horn was detected by Western blot method; the autophagosomes and ultrastructure in spinal dorsal horn neurons were observed by electron microscope.@*RESULTS@#After the treatment, compared with the sham operation group, in the model group, the gait score was increased and the mechanical pain threshold was decreased (P<0.01), and the expression of GRP78 protein in spinal dorsal horn was increased (P<0.01). Compared with the model group and the wheat-grain moxibustion+3-MA group, in the wheat-grain moxibustion group, the gait score was decreased and mechanical pain threshold was increased (P<0.01), and the expression of GRP78 protein in spinal dorsal horn was decreased, and the expressions of mRNA and protein of Beclin-1 were increased (P<0.01). Under electron microscope, the ultrastructure of spinal dorsal horn neurons in the wheat-grain moxibustion group was not significantly damaged, and its structure was basically close to normal, and the number of autophagosomes was more than the other three groups.@*CONCLUSION@#Wheat-grain moxibustion at "Dazhui" (GV 14) has analgesic effect on CSR rats. The mechanism may be related to moderately up-regulate the expression of Beclin-1, enhance autophagy and reduce endoplasmic reticulum stress.

High Expression of Bone Marrow VEGF in Patients with Acute Leukemia and Its Correlation with Prognosis / 中国实验血液学杂志

OBJECTIVE@#To detect the level of vascular endothelial growth factor (VEGF) in bone marrow of patients with non-M3 acute leukemia (AL), and estimate its relationship with prognosis.@*METHODS@#From January 2016 to December 2019, 114 patients with AL in department of Hematology, Wuwei People's Hospital were selected as study group, and 25 healthy volunteers were enrolled as control group. The concentration of VEGF in bone marrow was detected by ELISA. The patients were divided into high and low concentration group according to the level of VEGF. The overall survival (OS) and event-free survival (EFS) were compared among different groups.@*RESULTS@#The level of VEGF in patients with AL was significantly higher than that in the control group. The median OS and EFS in the low concentration group was 34.5 and 32 months, respectively, while, in the high concentration group was 30 and 26 months, respectively. The differences between the two groups were statistically significant (P=0.010). There were significant differences in OS rate (P=0.035) and EFS rate (P=0.026) between low and high concentration group. Multivariate analysis showed that high VEGF concentration was an independent risk factor affecting OS (HR=2.619, 95%CI 1.070-6.406, P=0.035) and EFS (HR=2.221, 95%CI 1.074-4.552, P=0.031) in AL patients.@*CONCLUSION@#VEGF highly expresses in the bone marrow of patients with AL at initial diagnosis and relapse, and shows adverse effects on the prognosis.

Regulation Effect of Myeloid Leukemia No.1 Chinese Herb Medicine Prescription Combined with Chemotherapy on Th17 Cells in Bone Marrow of Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the regulation effect of myeloid leukemia No.1 Chinese herb medicine prescription combined with chemotherapy on Th17 cells in bone marrow fluid of AML patients, so as to provide guidance for improving AML treatment effect and patients' long-term survival.@*METHODS@#Seventy patients with AML who were hospitalized in Department of Hematology, Wuwei People's Hospital from April 2017 to August 2019 were selected and enrolled in AML group, 25 healthy volunteers were selected and enrolled in control group; then according to therapeutic regimen, AML patients were divided into 2 groups: combined therapy group (myeloid leukemia NO.1 Chinese herb medicine prescription combined with chemotherapy) and non-combined therapy group (chemotherapy alone). Flow cytometry was used to detect the ratio of CD3@*RESULTS@#The ratio of CD3@*CONCLUSION@#Th17 cells expression in bone marrow of newly diagnoses and relapsed AML patients significantly increase, and decrease significantly after treatment. Myeloid leukemia No.1 Chinese herb prescription combined with chemotherapy can significantly increase the CR rate and reduce the RL rate for AML.

Huanglian Ejiao Decoction formula syndrome and its application for refractory insomnia / 中国中药杂志

Huanglian Ejiao Decoction,firstly recorded in Treatise on Febrile Diseases,could be used to treat heat-conversion syndrome of Shaoyin. It has been identified that,the indications of Huanglian Ejiao Decoction include:(1)in modern medicine,it can be used to treat insomnia,arrhythmia,oral ulcer,Xiali,blood syndrome and other diseases;(2)in terms of symptoms and signs,it is mainly used for restlessness,ritability,insomnia,extremely difficult to fall asleep,palpitation,atrial premature beat,ventricular premature beat and other arrhythmias,stomach distension and stuffiness,stomach pain,vomiting,abdominal pain,cramps,lower edge,constipation,blush,red lips,easy bleeding,red tongue,thin or no coating,dry tongue surface,or light red tongue,or dark red,thin white tongue coating,and rapid pulse. It has been also identified that,(1)although the original statement of Huanglian Ejiao Decoction is very simple,it can not only be used according to irritability and insomnia;(2)tongue image is not the key to syndrome differentiation of this prescription;(3)the essence of Shaoyin syndrome is not completely heart kidney Yang deficiency,which is closest to shock in modern medicine,including septic shock,hypovolemic shock and cardiogenic shock;(4)the essential difference between Shaoyin cold and heat conversion syndrome of Shaoyin lies in the different types of shock,in which cardiogenic shock is the main cold type,while septic shock is the main heat shock;(5)heat-conversion syndrome of Shaoyin is more common in the late stage of septic shock,and part of it can be seen in the stage of heart failure combined with sympathetic activation;(6)Dioscoreae Rhizoma and Rehmanniae Radix are often used to replace egg yolk;(7)Huanglian Ejiao Decoction takes effect quickly and the course of treatment is short.