1.Autophagy and beyond: Unraveling the complexity of UNC-51-like kinase 1 (ULK1) from biological functions to therapeutic implications.
Ling ZOU ; Minru LIAO ; Yongqi ZHEN ; Shiou ZHU ; Xiya CHEN ; Jin ZHANG ; Yue HAO ; Bo LIU
Acta Pharmaceutica Sinica B 2022;12(10):3743-3782
UNC-51-like kinase 1 (ULK1), as a serine/threonine kinase, is an autophagic initiator in mammals and a homologous protein of autophagy related protein (Atg) 1 in yeast and of UNC-51 in Caenorhabditis elegans. ULK1 is well-known for autophagy activation, which is evolutionarily conserved in protein transport and indispensable to maintain cell homeostasis. As the direct target of energy and nutrition-sensing kinase, ULK1 may contribute to the distribution and utilization of cellular resources in response to metabolism and is closely associated with multiple pathophysiological processes. Moreover, ULK1 has been widely reported to play a crucial role in human diseases, including cancer, neurodegenerative diseases, cardiovascular disease, and infections, and subsequently targeted small-molecule inhibitors or activators are also demonstrated. Interestingly, the non-autophagy function of ULK1 has been emerging, indicating that non-autophagy-relevant ULK1 signaling network is also linked with diseases under some specific contexts. Therefore, in this review, we summarized the structure and functions of ULK1 as an autophagic initiator, with a focus on some new approaches, and further elucidated the key roles of ULK1 in autophagy and non-autophagy. Additionally, we also discussed the relationships between ULK1 and human diseases, as well as illustrated a rapid progress for better understanding of the discovery of more candidate small-molecule drugs targeting ULK1, which will provide a clue on novel ULK1-targeted therapeutics in the future.
2.Application value of phase contrast MR angiography in assessment of the functional posterior communicating artery in patients with posterior circulation ischemia
Wei ZHOU ; Zhengjie CHEN ; Minru LU ; Jun LI ; Feng CHEN ; Jiali ZHANG
Chinese Journal of Radiology 2020;54(4):332-337
Objective:To investigate the application value of phase contrast MR angiography (PC MRA) in quantitative assessment for the hemodynamic features of functional posterior communicating artery (F-PCoA) in the patients with posterior circulation ischemia (PCI).Methods:Data of PC MRA in our Hospital from April 2015 to March 2017 were collected retrospectively. Twenty-six patients (PCI group) were diagnosed as PCI with F-PCoA, and other 25 patients were defined as non-PCI group including 10 patients with F-PCoA (non-PCI group 1) and 15 patients without F-PCoA (non-PCI group 2). The cross-sectional area, mean flux, mean velocity, minimum flux, maximum flux, minimum velocity, and maximum velocity were recorded, and the peak height of flux (maximum flux-minimum flux) and peak height of velocity (maximum velocity - minimum velocity) of basilar artery (BA) were calculated. The subtype, cross-sectional area, mean flux, mean velocity, blood flow direction, and absolute flux of F-PCoA in anterior-posterior direction(sum of both sides)were recorded and analyzed statistically.Results:The F-PCoA of 36 cases in PCI group and non-PCI group 1 were divided into three types: type A: the F-PCoA was consistent with anatomical posterior communicating artery (A-PCoA), accounting for 83.3%(30/36 cases); type B: the F-PCoA was not consistent with A-PCoA, accounting for 13.9%(5/36 cases);and type C: a mixed type with the F-PCoA was consistent with A-PCoA in only one side, accounting for 2.8%(1/36 cases). There were no significant differences in the composition of F-PCoA subtype (χ 2=0.609, P=0.737) and the absolute flux of F-PCoA in anterior-posterior direction( t=-0.576, P=0.568) between PCI group and non PCI group 1. It could be unidirectional or bidirectional blood flow forasingle F-PCoA during a cardiac cycle. The blood flow direction of bilateral F-PCoA was similar or not in one single case. The obviously main wave peak of the absolute flux curve of F-PCoA in anterior-posterior direction in PCI group were observed. There was a significant difference in the cross-sectional area of BA between non PCI group 1 and 2( t=-2.856, P=0.009), however no significant differences were found in the genders, mean flux, mean velocity, minimum flux, maximum flux, peak height of flux, minimum velocity, maximum velocity, and peak height of velocity of BA. Conclusions:PC MRA can be used to quantificationally assess the hemodynamic characteristics of F-PCoA such as flow direction, velocity and flux direction, absolute flux in anterior-posterior direction and morphological changes of F-PCoA, which may provide more information for the PCI diagnosis and treatment.
3.Introduction of 169 Single-flavored Drugs Included in The Ayurvedic Pharmacopoeia of Indian
Ming SUN ; Minru JIA ; Zhang WANG ; Tingting KUANG ; Yi ZHANG ; Yong ZENG
China Pharmacy 2019;30(15):2075-2091
OBJECTIVE: To analyze the characteristics of 169 single-flavored drugs in The Ayurvedic Pharmacopoeia of Indian, and to provide reference for China to expand new drug sources and study new indications. METHODS: Sanskrit drug names, botanical names (family names), Chinese medicine names, medicinal parts, therapeutic uses in Ayurveda, distributions in India, distributions or cultivations (introductions) in other countries and regions, the main treatments of other countries and regions were introduced comprehensively, so as to analyze the distribution, family names characteristics, medicinal part and indication characteristics of 169 single-flavored drugs. RESULTS: Totally 169 single-flavored drugs were mostly distributed in tropical and subtropical regions. There were 116 single-flavored drugs distributed throughout India (including introduction or cultivation) and medicinal; while 51 single-flavored drugs were only distributed in India; 21 single-flavored drugs were distributed and used in China; 10 single-flavored drugs have a distribution in China but have not been used; only one single-flavored drug had been used in China but had no distribution. Yunnan, Guangdong, Guangxi, Fujian were provinces (districs) where Ayurveda single-flavored drug was planted and used more frequently. Sri Lanka, Vietnam and Malaysia were countries where Ayurveda single-flavored drug was planted and used more frequently. The original plants of the 169 single-flavored drugs were derived from Euphorbiaceae and Dipterocarpaceae, Umbelliferae and Morus, etc. More roots and rhizomes were used. The types of commonly treatment diseases were digestive diseases, respiratory diseases, “symptoms, signs, and clinical and laboratory abnormalities, which cannot be classified elsewhere”, skin and subcutaneous tissue diseases, genitourinary system diseases, blood diseases, etc. The diseases with characteristic diagnosis and treatment were caused by imbalance of body wind, intermittent heat, imbalance of mucin and imbalances of three diseases. CONCLUSIONS: 169 single-flavored drugs in this paper are distributed in tropical and subtropical regions, and are often used to treat digestive diseases. This study can provide reference for the introduction and cultivation of Ayurveda single-flavored drug and for the development of new drug sources and new uses in China.
4.Study on Varieties,Indications and Usage Features of Tibetan Medicine Preparations Based on Drug Stan-dards
Tingting KUANG ; Ming SUN ; Zhang WANG ; Xiaoqi ZHU ; Yanhong TANG ; Mengdie CAO ; Yong ZENG ; Minru JIA ; Yi ZHANG ; Daofeng JIANG
China Pharmacy 2017;28(16):2231-2234
OBJECTIVE:To study varieties,indications and usage features of Tibetan medicine preparations,and provide refer-ence for the clinical treatment and new drug development for Tibetan medicine. METHODS:Tibetan medicine preparations in offi-cial standards were collected,variety features(formula scale,license number,pharmaceutical enterprise,name and dosage form, herbal medicine number),action features(indication name,clinical application)and medicine features(category and quantity,me-dicinal part,commonly used drug,frequency,three fruitsuse feature) were summarized. RESULTS:Totally 458 preparations were included,including 18 recorded in Chinese Pharmacopoeia (part 1,2015 edition),200 recorded in Pharmaceutical Stan-dards of the Ministry of Health of China(Tibetan medicine,1995 edition),240 recorded in Tibetan Medicine Standards(six prov-inces). 129 had obtained 430 license numbers,from 52 pharmaceutical companies;the prearations were mainly named byherbal medicine+principal medicine+dosage formprincipal medicine+dosage formandindication+dosage form. Dosage forms had powder,pill,cream,oil,syrup and wine; the number of herbal medicine was(13.81±13.28). The Tibetan preparations were com-monly used in the clinical treatment of diseases of the digestive system,respiratory system,genitourinary system,circulatory sys-tem,infectious and parasitic diseases,etc. 442 medicines had been used,including 297 herbal medicines,70 animal medicines, 47 mineral medicines and other 28 medicines. The common medicinal parts were seed or fruit,root or rhizome,whole grass,flow-er,stem,over-ground part,tuber or bulb,etc. The top 10 frequency of medicines were as follows as Terminalia chebula,Cartha-mus tinctorius,Aucklandia lappa,Amomum kravanh,Phyllanthus emblica,Piper longum,Inula racemosa,Punica granatum, Moschus berezovskii,Adhatoda vasica;and 19% preparations contained three fruits(T. chebula,P. emblica,Terminalia bellirica). CONCLUSIONS:Tibetan medicine preparations have rich varieties,reasonable herbal medicines,more solid preparations,widely clinic application,contain more herbal drugs and commonly usethree fruits,while fewer preparations have obtained license number.
5.Species and Use of Current Chinese Minority Medicine
Minru JIA ; Yi ZHANG ; Zhuyun YAN ; Yuying MA ; Xianrong LAI ; Zhang WANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2015;(7):1546-1550
This article was aimed to survey the use of Chinese minority medicine, in order to provide differences and similarities among different Chinese minority medicine, and to analyze the relations among species resources, using range, functions and indications. It provided a basic scientific platform for the development, research and use of minority medicine. The books and journals published since the late 1970s (the country after the reform and opening up) had been collected, classified. And reference books on current Chinese minority medicine had been compiled. The results showed that the first draft of the book had been completed and delivered to the press. The dictionary had cited 53 traditional medicine used by minority groups. The total number of minority medicine was 7 734. The total characters amount in the book was 1 700 000 words. It was concluded that the species of minority medicine were various. There was rich information on their harvest, medicinal parts, functions and indications with prominent features. The existing major problems were to clarify the standard of the species as well as their major functions and indications.
6.Long-term follow-up and outcome of patients who survived more than 7 years after liver transplantation:a single-center analysis
Binsheng FU ; Minru LI ; Tong ZHANG ; Shuguang ZHU ; Hua LI ; Shuhong YI ; Genshu WANG ; Jian ZHANG ; Nan JIANG ; Chi XU ; Yang YANG ; Guihua CHEN
Chinese Journal of Organ Transplantation 2012;33(9):552-555
Objective To investigate the occurrence and prevention measures of long term complications in long term survival recipients after liver transplantation.Methods In the recipients undergoing liver transplantation from Sept. 2003 to Dec. 2004,by Nov. 30,2011,there were 62 cases with the survival time more than seven years.The clinical data and follow up examination results of these 62 cases were retrospectively,including weight,blood pressure,blood sugar,blood lipids,and liver and kidney functions. The incidence of long-term complications was statistically tested.Results Postoperative metabolic complications including overweight or obese occurred in 21 cases (33.9%), new onset diabetes in18 patients (29%), hyperlipidemia in 17 cases (27.4%),hypertension in 9 cases ( 14.5 % ),and kidney dysfunction in 12 patients ( 19.4% ).The incidence of diabetes and hyperlipidemia in the patients with overweight and diabetes (respectively 52.4% and 42.9%) was significantly higher than in the normal weight group (respectively 17.1 % and 19.5 %)(P<0.05).In 58 recipients with primary diseases of hepatitis B-related liver diseases,one case had hepatitis B virus reinfection. In 17 recipients with primary disease of primary liver cancer,tumor recurrence occurred in 2 cases.During the follow up period,4 patients received liver re-transplantation due to hepatic artery stenosis (1 case) or biliary complications-induced loss of the transplanted liver function (3 cases).Conclusion The major complications of the long term survival recipients after liver transplantation are metabolic complications and primary disease relapse. Postoperative long-term follow up and monitoring of recipients is recommended to prevent and treat a variety of long-term complications.
7.Effects of early developed sepsis on postoperative immune status in patients undergoing liver transplantation
Minru LI ; Genshu WANG ; Qi ZHANG ; Huimin YI ; Guihua CHEN
Chinese Journal of General Surgery 2012;27(6):467-470
Objective To investigate immune status changes in liver transplant patients suffering from early developed sepsis.Methods In this study 19 patients undergoing liver transplantation for severe hepatitis from Oct 2008 to Jul 2009 were enrolled.Immune status was compared between patients of severe hepatitis and 20 healthy volunteers.According to whether early sepsis developed or not,patients were divided into sepsis group (HSS) and non-sepsis group (HSNS).T lymphocyte subgroups of the peripheral blood were compared between post-transplant and pre-transplant in these two groups on different stages.Results Comparing to volunteers,T% and IFN-γ/IL-4 of severe hepatitis patients significantly decreased,CD4 + CD25 + Foxp3 + Treg( % ),Foxp3 mRNA and IL-10 significantly increased.Early sepsis developed in 9 patients.Compared with pre-transplant levels,T% in both groups significantly decreased on the first day post transplant.T% in HSNS group increased to the level of pretransplant while T% of HSS group remained at the low level.Treg% ( t =3.265,P =0.004 ) and Foxp3 mRNA ( t =2.750,P =0.013 ) of HSNS group on day 14 decreased significantly lower than that before transplantation.Those two parameters of HSS group even increased slightly.IFN-γ/IL-4 in HSNS group increased significantly on day 3 (t =2.261,P =0.036),while there was no change in HSS group.The concentration of IL-10 in both groups significantly decreased,and the level in HSNS group remained at a low level,while that in HSS group increased on day 14.Conclusions Patients with severe hepatitis have weakened immune status.The imbalance of immune status recovers gradually since 7-14 days after transplantation in patients uncomplicated with sepsis.However,the immune status of receipients complicated with sepsis fails to improve.
8.Clinical outcomes in the use of mycophenolate mofeil in liver transplant patients with chronic renal dysfunction
Yuling AN ; Changjie CAI ; Tingting ZHANG ; Minru LI ; Huimin YI ; Guihua CHEN
Chinese Journal of Hepatobiliary Surgery 2011;17(11):894-897
ObjectiveTo evaluate the effect of mycophenolate mofeil (MMF) combined with dose-decreased calcineurin inhibitors (CNIs) in patients who received liver transplanation with chronic kidney malfunction.Methods28 liver transplant patients with chronic kidney malfunction were prospectively included in this study.MMF was initiated and the dose of the original immunosuppressive drug CNIs decreased.The change in renal function and adverse events were evaluated.ResultsOne patient was discontinued with MMF treatment because of serious myelosuppression.The other 27 patients were treated with MMF with a median of 30.8 months.The basal creatinine values and the basal creatinine clearance were ( 134.26 ± 27.25) μmol/1 and (57.70 ± 16.93) ml/min,respectively.The basal glomerular filtration rate was (53.91±11.63) ml/min.The creatinine values at 1,3,6,12,24 and 36 months were 124.30±28.27 (P=0.006),130.19±29.29 (P=0.174),125.49±38.18 (P=0.194),119.71±31.36 (P=0.010),137.43±42.55 (P=0.804),and (139.04±39.80) μmol/L (P=0.916).And the creatinine clearance values at 1,3,6,12,24 and 36 months were 62.57±19.29 (P=0.008),61.18± 19.70 (P=0.086),64.27±22.82 (P=0.018),67.48±22.59 (P=0.002),57.18±19.55 (P=0.405),and (54.56±23.48) ml/minute (P=0.708),respectively.The glomerular filtration rate at 1,3,6,12,24 and 36 months were 59.20 ± 14.05 (P=0.006),56.61±14.01 (P=0.04),60.47±17.33 (P=0.016),63.59±17.66 (P=0.002),53.75±13.60 (P=0.369),and (51.70±16.07) ml/min (P=0.703).One patient (3.7%) had mild acute rejection.5 patients (18.5 % ) had mild abdominal distention or diarrhea.2 patients (7.4%) had ischemic cholangitis.No patient had cytomegalo virus infection or tumor recurrence.ConclusionIn liver transplant recipients with chronic renal dysfunction,MMF allowed CNIs dose reduction or discontinuation,improved or stabilized renal function in most patients and it had only mild adverse events.
9.Effect of different anesthetic techniques on perioperative changes in T-lymphocyte subsets in patients with cardia cancer
Xiaojia ZHANG ; Qinqing HU ; Hongqing LI ; Minru DENG
Chinese Journal of Postgraduates of Medicine 2010;33(30):14-16
Objective To observe the effects of different anesthetic techniques on T-lymphocyte subsets in patients with cardia cancer. Methods Thirty-two patients undergoing elective radical operation for cardia cancer who had been average assigned into two groups by random digits table, group Ⅰ :general anesthesia;group Ⅱ :epidural anesthesia combined with general anesthesia (16 cases in each group).Peripheral blood T-lymphocyte subsets were measured before induction, after anesthesia, end of operation, 1d,3 d after operation. Results CD3,CD4,CD8 and CD4/CD8 all decreased in two groups after anesthesia,end of operation and 1 d after operation than before induction (P < 0.05). The index almost returned to the baseline values at 3 d after operation in group Ⅱ [ (60.75 ± 4.22 )%, (39.65 ± 3.64)%, (25.90 ± 1.17 )%,1.57 ±0.15](P >0.05),while in group Ⅰ still lower [(55.83 ±5.20)%, (35.15 ±5.65)%, (23.00 ±1.03 )%, 1.47 ± 0.35 ](P< 0.05 ). The two groups ontrast had significant deviation at 3 d after operation (P<0.05). Conclusion Epidural anesthesia combined with general anesthesia can reduce depression of Tlymphocyte subsets induced by surgical trauma and anesthesia.
10.Effects of different anesthetic techniques on perioperative changes in T-lymphocyte subsets in patients with esophageal carcinoma
Qinqing HU ; Hongqing LI ; Xiaojia ZHANG ; Minru DENG ; Qinquan JI ; Lijuan WU
Chinese Journal of Primary Medicine and Pharmacy 2008;15(4):538-539
Objective To determine the effects of different anesthetic techniques on T-lymphocyte subsets in patients with esophageal carcinoma. Methods Forty patients were randomly assigned into general anesthesia group (group Ⅰ),or combined generae anesthesia with epidural anesthesia group(group Ⅱ). Peripheral blood CD3, CD4,CD8 were measured before induction ( T1 ), after anesthesia ( T2 ), end of operation ( T3 ), 1d ( T4 ), 3d ( T5 ) after surgery. Resolts CD3,CD4,CD8,CD4/CD8 decreased at T2 in the two groups. In group Ⅱ ,CD3,CD4,CD8,CD4/CD8 ratio almost returned to the baseline values at T4 ,while group Ⅰ did not. Conclusion Epidural anesthesia combined with general anesthesia can reduce depression of T-lymphocyte subsets induced by surgical trauma and anesthesia, and is the anesthetic tecnique of choice for cancer patients undergoing major operation.

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