CenhANCER: a comprehensive cancer enhancer database for primary tissues and cell lines.

Enhancers, which are key tumorigenic factors with wide applications for subtyping, diagnosis and treatment of cancer, are attracting increasing attention in the cancer research. However, systematic analysis of cancer enhancers poses a challenge due to the lack of integrative data resources, especially those from tumor primary tissues. To provide a comprehensive enhancer profile across cancer types, we developed a cancer enhancer database CenhANCER by curating public resources including all the public H3K27ac ChIP-Seq data from 805 primary tissue samples and 671 cell line samples across 41 cancer types. In total, 57 029 408 typical enhancers, 978 411 super-enhancers and 226 726 enriched transcription factors were identified. We annotated the super-enhancers with chromatin accessibility regions, cancer expression quantitative trait loci (eQTLs), genotype-tissue expression eQTLs and genome-wide association study risk single nucleotide polymorphisms (SNPs) for further functional analysis. The identified enhancers were highly consistent with accessible chromatin regions in the corresponding cancer types, and all the 10 super-enhancer regions identified from one colorectal cancer study were recapitulated in our CenhANCER, both of which testified the high quality of our data. CenhANCER with high-quality cancer enhancer candidates and transcription factors that are potential therapeutic targets across multiple cancer types provides a credible resource for single cancer analysis and for comparative studies of various cancer types. Database URL http://cenhancer.chenzxlab.cn/.

Two new meroterpenoids from the bark of Cinnamomum cassia and their antioxidant activity.

Two new (1 and 2) meroterpenoids were isolated from the bark of Cinnamomum cassia. Their structures were determined by spectroscopic analyses and chemical methods. Antioxidant activities of 1 and 2 were evaluated by the ORAC and DPPH radical scavenging assays, and the results revealed that compound 2 displayed oxygen radical absorbance capacity. The discovery of compounds 1 and 2 added new members of this kind of natural product.

[Clinical efficacy and time-effect relationship of dynamic qi acupuncture for acute lumbar sprain].

OBJECTIVE: To observe the clinical efficacy of dynamic qi acupuncture for acute lumbar sprain, and to explore the differences of different needle retention time on the improvement of pain, lumbar mobility and lumbar dysfunction. METHODS: A total of 160 patients with acute lumbar sprain were randomly divided into an observation group A (40 cases, 4 cases dropped off), an observation group B (40 cases, 2 cases dropped off), an observation group C (40 cases, 4 cases dropped off) and a medication group (40 cases, 6 cases dropped off). The patients in the observation group A, the observation group B and the observation group C were treated with acupuncture at "lumbago point" and Sanjian (LI 3) on the left side, and during the needles were kept for 10, 20 and 30 min respectively, the patients were required to take tolerable lumbar active activities, once a day; the patients in the medication group were treated with celecoxib capsules, 0.2 g each time, twice a day. All the patients were treated for 5 d. Before and after treatment, the scores of numerical rating scale-11 (NRS-11), lumbar range of motion (ROM) and modified Oswestry disability index (ODI) were observed, and the clinical efficacy of each group was evaluated. RESULTS: After treatment, the scores of NRS-11, ROM and ODI in each group were decreased compared before treatment (P<0.01). The decreased degree of NRS-11, ROM and ODI in each observation group was greater than that in the medication group (P<0.05), and the decreased degree of ROM and ODI in the observation group B and the observation group C was greater than that in the observation group A (P<0.05). The total effective rates were 94.4% (34/36) in the observation group A, 94.7% (36/38) in the observation group B and 97.2% (35/36) in the observation group C, respectively, which were higher than 79.4% (27/34) in the medication group (P<0.05). CONCLUSION: Dynamic qi acupuncture with needle retention for 10, 20 and 30 min all could effectively improve the pain, lumbar mobility and lumbar dysfunction in patients with acute lumbar sprain. If the lumbar dysfunction is severe, needle retention for 20 min or more is recommended.

[Protective effect and mechanism of electroacupuncture of "Biao-Ben" acupoints combination for mitochondrial dysfunction in diabetic nephropathy rats].

OBJECTIVE: To study the protective effect of electroacupuncture (EA) at "Biao"-acupoints, "Fenglong"(ST40) and "Zhongwan"(CV12), used for treating symptoms of the disease, and "Ben"-acupoints, "Zusanli"(ST36) and "Guanyuan"(CV4), for treating the root cause of the disease on oxidative stress injury of renal mitochondria through SIRT1/PGC-1α signal pathway in rats with diabetic nephropathy (DN). METHODS: A total of 33 male Wistar rats were randomized into normal (n=10), model (n=12) and EA (n=11) groups.The DN model was established by feeding the rats with high-sugar and high-fat diet for 6 weeks combined with streptozotocin (STZ, 35 mg/kg, i.p.). EA (4 Hz/60 Hz, 1 mA)was applied to ST36-ST40 and CV4-CV12 for 15 min, once every other day for 8 weeks. The rats' body weight was recorded, urine in 24 hours (24-h UP) was collected to measure the urine protein level, and the fasting blood glucose (FBG) level detected by using a glucometer. The levels of serum glycosylated hemoglobin (HbA1c), creatinine (Scr) and urea nitrogen (BUN) were assayed using immunoturbidi-metry, picric acid method and urease method, respectively, and those of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) detected using an automatic biochemical analyzer. The kidney tissue was collected for assaying the activity of superoxide dismutase (SOD) with xanthine oxidase method, glutathione (GSH) activity with dithio-dinitrobenzoic acid method, catalase （CAT） activity with ammonium molybdate spectrometric method, and malondialdehyde (MDA) content with thiobarbituric acid method. Histopathological changes of the kidney tissue were observed by microscope after hematoxylin-eosin staining (HE), periodate Schiff staining (PAS) and Masson staining, separately, and its subcellular structure was observed under transmission electron microscopy. The expression levels of renal SIRT1 and PGC-1α mRNAs and proteins were detected by quantitative real-time PCR and Western blot, and the immunoactivity of renal α-smooth muscle actin (α-SMA), and immunofluorescence density of renal collagen Ⅰ (Col Ⅰ), collagen Ⅳ(Col Ⅳ) and fibronec-tin (FN) detected by immunohistochemistry and immunofluorescence assay, respectively. RESULTS: Compared with the normal group, the levels of FBG, HbA1c, BUN, Scr, 24-h UP, TG, TC, LDL-C, MDA, α-SMA, Col Ⅰ, Col Ⅳ and FN proteins were significantly increased (P<0.01), and the levels of body weight, HDL-C, SOD, GSH, CAT, SIRT1 and PGC-1α mRNAs and proteins were decreased in the model group (P<0.01, P<0.05). In comparison with the model group, the levels of FBG, HbA1c, BUN, Scr, 24-h UP, TG, TC, LDL-C and MDA, and the expressions of α-SMA, Col Ⅰ, Col Ⅳ and FN proteins were markedly down-regulated (P<0.05, P<0.01), and those of body weight, HDL-C, SOD, GSH, CAT, and the expressions of SIRT1 and PGC-1α mRNAs and proteins significantly up-regulated (P<0.01, P<0.05) in the EA group. HE staining showed mesangial dilatation, glomerular hypertrophy and mesangial matrix accumulation; PAS staining showed an increase of the glomerular extracellular matrix deposition; and Masson staining displayed an enhancement of glomerular fibrosis and interstitial space expansion; and electron microscope revealed foot process fusion, basement membrane thickening and organelle injury in the rat's kidney of the model group, which were relatively milder in the EA group. CONCLUSION: EA of ST36-ST40 and CV4-CV12, "Biao-Ben" acupoints combination, can alleviate oxidative stress and mitochondrial dysfunction in DN rats, which may be associated with its functions in up-regulating SIRT1/PGC-1α signaling, and decreasing renal fibrosis.

[Electroacupuncture preconditioning alleviates renal injury and oxidative stress through Sirt3/MnSOD pathway in type 2 diabetic rats].

OBJECTIVE: To explore the protective effect and molecular mechanism of electroacupuncture (EA) preconditioning on renal injury in type 2 diabetic rats. METHODS: Fifty male Wistar rats were randomly divided into control, model, EA, EA+inhibitor, and inhibitor groups, with 10 rats in each group. Diabetes model was established by high fat and high glucose diet and intraperitoneal injection of streptozotocin (40 mg/kg). EA (2 Hz, 1 mA) preconditioning was applied to "Guanyuan" (CV4), "Zhongwan" (CV12), bilateral "Zusanli" (ST36) and "Fenglong" (ST40) for 15 min, once every other day for 8 weeks. Rats of the inhibitor and EA+inhibitor groups were given intraperitoneal injection of 3-TYP (50 mg/kg) once every other day for a total of 3 times. The body weight, kidney mass, and renal index were recorded. The contents of urine microalbumin (ALB), 24 h urine 8-hydroxydeoxyguanosine (8-OHdG) and activities of reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), glutathione glycine peroxidase (GSH-Px) in kidney were detected by ELISA. The activities of mitochondrial respiratory chain enzyme complex (RCCⅠ-RCCⅣ) in kidney were detected using spectrophotometric method. HE staining, Masson staining and transmission electron microscopy were used to observe the changes of renal structure. The protein and mRNA expressions of silent information regulator 3 (Sirt3), manganese superoxide dismutase (MnSOD) in kidney were detected by Western blot and quantitative real-time PCR, respectively. RESULTS: After modeling and compared with the control group, the contents of ALB, the renal index, activity of ROS and content of 8-OHdG, and the renal collagen volume fraction (CVF) were increased (P<0.01), while the activities of SOD, CAT and GSH-Px, RCCⅠ-RCCⅣ, and the mRNA and protein expressions of Sirt3 and MnSOD were decreased (P<0.01). After the treatment and compared with the model group, the contents of ALB, the renal index, ROS, 8-OHdG, and the CVF were decreased in the EA group(P<0.01, P<0.05), while the activities of SOD, CAT, GSH-Px, RCCⅠ-RCCⅣ, and Sirt3 and MnSOD expression levels were increased (P<0.01, P<0.05)；the RCCⅡ activity and the expression level of MnSOD mRNA were increased (P<0.05) in the EA+inhibitor group; the ALB and 8-OHdG contents and the CVF in the inhibitor group were increased (P<0.05), while the activity of SOD, and Sirt3 and MnSOD expression levels were decreased (P<0.05). In comparison with the EA group, the contents of ALB, the renal index, activities of ROS and 8-OHdG contents, and the CVF were increased (P<0.05, P<0.01), activities of SOD, CAT and GSH-Px and RCCⅠ and RCCⅡ, and the mRNA and protein expressions of Sirt3 and MnSOD were decreased (P<0.05, P<0.01) in both EA+inhibitor group and inhibitor group, whereas the activities of RCCⅢ and RCCⅣ were decreased in the inhibitor group (P<0.05). The therapeutic effect of inhibitor was notably inferior to that of EA+inhibitor in decreasing ALB and 8-OHdG contents, and CVF (P<0.01), and in up-regulating SOD and RCCⅡ activities, Sirt3 and MnSOD expression levels (P<0.01, P<0.05). CONCLUSION: EA preconditioning can increase the expressions of renal Sirt3 and MnSOD in type 2 diabetic rats, thereby reducing the oxidative stress response and protecting the kidneys.

Astramalabaricosides A-T, Highly Oxygenated Malabaricane Triterpenoids with Migratory Inhibitory Activity from Astragalus membranaceus var. mongholicus.

Twenty new malabaricane triterpenoids, astramalabaricosides A-T (1-20), were isolated from the roots of Astragalus membranaceus var. mongholicus (Astragali Radix). Their structures were determined by spectroscopic analysis, and the use of the circular dichroism exciton chirality method, quantum chemical calculations, and chemical methods. Malabaricane triterpenoids, an unusual group with the 6-6-5-tricyclic core, are distributed in plants (e.g., Simaroubaceae, Polypodiaceae, and Fabaceae), a marine sponge, and fungi, and their number obtained to date is limited. Compounds 1-20 were characterized as glycosides with a highly oxygenated side chain, and 13-20 were the first cyclic carbonate derivatives among the malabaricane triterpenoids. The stereocluster formed from the continuous hydroxylated chiral carbons in each highly oxygenated side chain and the 6-6-5-tricyclic core system were entirely segregated, and the independent identification of their stereoconfigurations required considerable effort. The migratory inhibitory and antiproliferative activities of 1-20 were evaluated by wound-healing and cell-viability assays, respectively. Most compounds showed significant migratory inhibitory activity, and a preliminary structure-activity relationship was developed. Malabaricane triterpenoids are being reported in the genus Astragalus for the first time.

[Clinical observation on filiform-fire needling of "Biaoben acupoint combination" for 33 cases of sequelae of coronavirus disease 2019 during recovery period].

OBJECTIVE: To observe the clinical therapeutic effect of filiform-fire needling of "Biaoben acupoint combination" on the sequelae of patients with coronavirus disease 2019 (COVID-19) during the recovery period. METHODS: A total of 33 patients with COVID-19 during the recovery period were treated with filiform-fire needling at the acupoints of Mingmen (GV 4), Shenzhu (GV 12), Gaohuang (BL 43), Zusanli (ST 36) and Shangjuxu (ST 37), etc., once every other day, 3 times a week, and 3 times was one course of treatment and totally 2 courses of treatment were required. The TCM symptom, Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) scores, pulmonary function indexes (forced vital capacity [FVC], forced expiratory volume in one second [FEV1], peak expiratory flow [PEF]) and chest CT imaging change were observed before and after treatment, and the therapeutic effect was evaluated. RESULTS: After treatment, the scores of TCM symptom, HAMA and HAMD were decreased compared with those before treatment (P<0.05), and the levels of FVC, FEV1 and PEF were increased compared with those before treatment (P<0.05), and the recovery rate of 22 patients with pulmonary ventilation dysfunction was 86.4% (19/22). After treatment, the lung shadow area was smaller than that before treatment (P<0.05). The effective rate of 25 patients with lung CT abnormalities was 84.0% (21/25). After treatment, 23 cases were cured, 5 cases were markedly effective, 4 cases were effective, 1 case was ineffective, the cured and markedly effective rate was 84.8%. CONCLUSION: The filiform-fire needling of "Biaoben acupoint combination" could significantly reduce the sequelae of cough, fatigue, chest tightness, etc. and mental symptoms such as anxiety and depression in patients with COVID-19 during the recovery period, and promote inflammatory exudation absorption of pulmonary lesion and improve lung ventilation function.

DSEATM: drug set enrichment analysis uncovering disease mechanisms by biomedical text mining.

Disease pathogenesis is always a major topic in biomedical research. With the exponential growth of biomedical information, drug effect analysis for specific phenotypes has shown great promise in uncovering disease-associated pathways. However, this method has only been applied to a limited number of drugs. Here, we extracted the data of 4634 diseases, 3671 drugs, 112 809 disease-drug associations and 81 527 drug-gene associations by text mining of 29 168 919 publications. On this basis, we proposed a 'Drug Set Enrichment Analysis by Text Mining (DSEATM)' pipeline and applied it to 3250 diseases, which outperformed the state-of-the-art method. Furthermore, diseases pathways enriched by DSEATM were similar to those obtained using the TCGA cancer RNA-seq differentially expressed genes. In addition, the drug number, which showed a remarkable positive correlation of 0.73 with the AUC, plays a determining role in the performance of DSEATM. Taken together, DSEATM is an auspicious and accurate disease research tool that offers fresh insights.

Bioactive pterocarpans from the root of Astragalus membranaceus var. mongholicus.

Eleven undescribed and three known pterocarpans were isolated and identified from the traditional Chinese medicine "Huang-qi", Astragali Radix (the root of Astragalus membranaceus var. mongholicus (Bunge) P.K.Hsiao). The structures of these pterocarpans were determined using spectroscopic, X-ray crystallographic, quantum chemical calculation, and chemical methods. Pterocarpans, almost exclusively distributed in the family of Leguminosae, are the second largest subgroup of isoflavanoids. However, pterocarpan glycoside number is limited, most of which are glucosides, and only one pterocarpan apioside was isolated from nature. Notably, nine rare apiosyl-containing pterocarpan glycosides were isolated and identified. The hypoglycemic activities of all these compounds were evaluated using α-glucosidase and DPP-IV inhibitory assays respectively, and some isolates displayed the α-glucosidase inhibitory function. The antioxidant activities of all compounds were evaluated using the ORAC and DPPH radical scavenging assays, respectively. All compounds exhibited varying degrees of oxygen radical absorbance capacity, and some compounds displayed DPPH radical scavenging ability.

[Electroacupuncture of "Biaoben acupoints" relieves kidney injury by suppressing oxidative stress in diabetic nephropathy rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of combined "Biao"- and "Ben"-acupoint (for treating symptoms and root causes of the disease, respectively) on the expression of kidney forkhead box O1 (FoxO1) and peroxi-some proliferator-activated receptor-γ coactivator-1α (PGC-1α) in diabetic nephropathy (DN) rats, so as to explore its potential mechanisms underlying improvement of DN. METHODS: Wistar rats were randomly divided into normal control (n=10), DN model (n=12), EA (n=11), EA+inhibitor (AS1842856 targeting FoxO1, n=11) and inhibitor (n=11) groups. The DN model was established by high fat and high glucose diet for 6 weeks and intraperitoneal injection of streptozotocin (55 mg/kg). EA (2 Hz, 1 mA) was applied to bilateral "Zusanli"(ST36), "Guanyuan"(CV4), "Fenglong" (ST40) and "Zhongwan"(CV12) for 15 min, once every other day for 8 weeks. The body mass was recorded, and blood glucose detected. The serum was sampled for detecting creatinine (Scr) content with Jaffe's assay, urea nitrogen (BUN) content with urease method. Urine albumin (ALB) and renal reactive oxygen species (ROS) contents were detected with ELISA, renal superoxide dismutase (SOD) activity with xanthine oxidase method, and renal malondialdehyde (MDA) content with thiobarbituric acid method. The renal subcellular structure was observed under transmission electron microscopy, and the expression levels of PGC-1α and FoxO1 proteins in the kidney tissue were detected using Western blot. RESULTS: Compared with the normal control group, the levels of body mass, SOD activity, and FoxO1 and PGC-1α protein expression were significantly reduced (P<0.01), while the contents of blood glucose, and serum Scr and BUN, urine ALB, renal MDA and ROS levels significantly increased in the model group (P<0.01). In comparison with the model group, the levels of body mass, SOD activity, and FoxO1 and PGC-1α expression were significantly increased in the three treatment groups except SOD, expression of FoxO1 and PGC-1α in the inhibitor group (P<0.01, P<0.05), and the contents of blood glucose, Scr, BUN, ALB, MDA and ROS were obviously decreased in the three treatment groups except ALB and ROS in the inhibitor group (P<0.01, P<0.05). The therapeutic effect of EA was notably superior to that of EA+inhibitor and inhibitor in increasing body mass, SOD activity, and FoxO1 and PGC-1α expression levels (P<0.05, P<0.01), and in down-regulating blood glucose, BUN, ALB and ROS levels (P<0.05, P<0.01), suggesting a reduction of the therapeutic effect of EA after administration of the inhibitor AS1842856 of FoxO1. Results of electron microscopy showed diffusely thickened and vague basement membrane, increased mesangial matrix, fused foot process, and reduced volume of endothelial cells with pykno-tic nucleus of the kidney tissue in the model group, which was obviously milder in both EA and EA+inhibitor groups particularly in the EA group. CONCLUSION: EA increases the expression of FoxO1 and PGC-1α in the kidneys of DN rats, thereby reducing the oxidative stress response and protecting the kidneys.

Hepatoprotective Effect of Oplopanax elatus Nakai Adventitious Roots Extract by Regulating CYP450 and PPAR Signaling Pathway.

O. elatus Nakai is a traditional medicine that has been confirmed to exert effective antioxidant and anti-inflammatory functions, and is used for the treatment of different disorders. However, its potential beneficial effects on drug induced hepatotoxicity and relevant molecular mechanisms remain unclear. This study investigated the protective effect and further elucidated the mechanisms of action of O. elatus on liver protection. O. elatus chlorogenic acids-enriched fraction (OEB), which included chlorogenic acid and isochlorogenic acid A, were identified by HPLC-MS/MS. OEB was administrated orally daily for seven consecutive days, followed by a single intraperitoneal injection of an overdose of APAP after the final OEB administration. The effects of OEB on immune cells in mice liver were analyzed using flow cytometry. APAP metabolite content in serum was detected using HPLC-MS/MS in order to investigate whether OEB affects CYP450 activities. The intestinal content samples were processed for 16 s microbiota sequencing. Results demonstrated that OEB decreased alanine aminotransferase, aspartate aminotransferase contents, affected the metabolism of APAP, and decreased the concentrates of APAP, APAP-CYS and APAP-NAC by inhibiting CYP2E1 and CYP3A11 activity. Furthermore, OEB pretreatment regulated lipid metabolism by affecting the peroxisome proliferator-activated receptors (PPAR) signaling pathway in mice and also increased the abundance of Akkermansia and Parabacteroides. This study indicated that OEB is a potential drug candidate for treating hepatotoxicity because of its ability to affect drug metabolism and regulate lipid metabolism.

[Thumb-tack needles based on "Biaoben acupoint compatibility" for sequela of COVID-19 during recovery period].

OBJECTIVE: To observe the effect of thumb-tack needles based on "Biaoben acupoint compatibility" on sequela symptoms, mental state and pulmonary ventilation function in patients with coronavirus disease 2019 (COVID-19) during recovery period. METHODS: Fifty cases of COVID-19 during recovery period were randomly divided into an observation group and a control group, 25 cases in each group. The patients in the observation group were treated with thumb-tack needles at Guanyuan (CV 4), Zusanli (ST 36) and Taiyuan (LU 9). The patients in the control group were treated with sham thumb-tack needles at identical acupoints as the observation group. The treatment in the two groups was given once a day, 7-day treatment was taken as a course of treatment, and totally two courses of treatment were given. The TCM symptom score, Hamilton anxiety scale (HAMA) score, Hamilton depression scale (HAMD) score, pulmonary function (forced vital capacity [FVC], forced expiratory volume in the first second [FEV1], peak expiratory flow [PEF]), the severity of pulmonary ventilation dysfunction and pulmonary imaging changes in the two groups were compared before and after treatment. RESULTS: Compared before treatment, the total scores and each item scores of TCM symptom scale, HAMA scores and HAMD scores in the two groups were reduced after treatment (P<0.05). Except for the symptom scores of dry throat and dry stool, the total score and each item score of TCM symptom scale, HAMA score and HAMD score in the observation group were lower than those in the control group (P<0.05). Compared before treatment, FVC, FEV1 and PEF in the two groups were increased after treatment (P<0.05), and those in the observation group were higher than the control group (P<0.05). The severity of pulmonary ventilation dysfunction in the two groups was reduced after treatment (P<0.05), and the severity in the observation group was better than that in the control group (P<0.05). After treatment, the lung shadow area in the two groups was decreased (P<0.05), and that in the observation group was smaller than the control group (P<0.05). The improvement of imaging change in the observation group was better than that in the control group (P<0.05). CONCLUSION: The thumb-tack needles based on "Biaoben acupoint compatibility" could significantly reduce the sequela symptoms, anxiety and depression in patients with COVID-19 during recovery stage, and improve the pulmonary ventilation function.

[Effect of electroacupuncture of "Biao-Ben" acupoints on renal function and hemorheology and eNOS level in patients with early diabetic nephropathy].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Biao-Ben acupoints" (Biao indicates pathogenic factors of disease; Ben refers to body constitution) on renal function, hemorheology and endothelial nitric oxide synthase (eNOS) level in patients with early diabetic kidney disease (DKD), so as to explore its mechanism underlying relieving early DKD. METHODS: A total of 120 patients with early DKD were selected and randomized into 3 groups: medication, conventional acupoints, and "Biao-Ben"acupoints groups by stratified randomization method, with 40 cases in each group. Patients of the me-dication group were treated by routine symptomatic supportive treatment (gleziquantel tablets or subcutaneous injection of insulin \[for hyperglycemia\], candesartan tablet \[hypertension\], simvastatin tablets \[hyperlipidemia\], etc.).Based on the medication group, patients of the conventional acupoint group were treated by EA of bilateral Feishu (BL13), Weiwanxiashu (EX-B3), Weishu (BL21), Shenshu (BL23), Sanyinjiao (SP6), Taixi (KI3) (main acupoints), etc., and those of the Biao-Ben acupoint group treated by EA of main acupoints Zhongwan (CV12), Fenglong (ST40), Xuehai (SP10) and Taichong (LR3) (Biao acupoints), and Guanyuan (CV4) and Zusanli (ST36) (Ben acupoints). The EA treatment was conducted one daily, 5 days a week for 8 weeks. The urine microprotein level in 24 h was detected using an automatic specific protein analyzer, followed by calcula-ting the urine albumin excretion rate (UAER). The serum creatinine (Scr), urea nitrogen (BUN) and cystatin (CysC) contents were detected by using an automatic biochemical analyzer, and the whole blood low-cut viscosity (ηbL), whole blood mid-cut viscosity (ηbM), whole blood high-cut viscosity (ηbH), plasma viscosity (ηp) and fibrinogen (FIB) levels were detected using an automatic hemorheology tester, and the serum eNOS and nitric oxide (NO) levels assayed using enzyme linked immunosorbent assay. The total clinical effective rates were compared and the adverse reactions of the treatment were recorded. RESULTS: Compared with the values before the treatment in each group, the levels of UAER, Scr, BUN, CysC, ηbL, ηbM, ηbH, ηp and FIB were all significantly decreased (P<0.01), while serum eNOS and NO levels significantly increased in the three groups after the treatment (P<0.01). Compared with the medication group, the levels of UAER, Scr, BUN, CysC, ηbL, ηbM, ηbH, ηp and FIB were notably lower (P<0.01, P<0.05), and serum eNOS and NO contents obviously higher in both the conventional acupoint and "Biao-Ben" acupoint groups (P<0.01). Comparison between the two EA groups showed that the levels of UAER, BUN, ηbL, ηbM, ηbH and ηp were lower (P<0.05), whereas the serum eNOS and NO contents were considerably higher (P<0.05) in the "Biao-Ben" acupoint group than in the conventional acupoint group. After the treatment, the total clinical effective rate of the "Biao-Ben" acupoint group was 89.74%(35/39), being significantly higher than those of both the conventional acupoint group (71.05%, 27/38,P<0.05) and medication group (64.10%, 25/39, P<0.05). CONCLUSION: EA of "Biao-Ben" acupoints can improve renal function and reduce microcirculation disorders in patients with early DKD, which may be related to its function in up-regulating the levels of serum eNOS and NO.

[Thumb-tack needle based on Biaoben Genjie theory for dry eye: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy of thumb-tack needle and sodium hyaluronate eye drops for dry eye. METHODS: A total of 60 patients with dry eye were randomly divided into a thumb-tack needle group and a western medication group, 30 cases in each group. Based on Biaoben Genjie theory, thumb-tack needle was applied at Zhiyin (BL 67), Lidui (ST 45), Fuyang (BL 59), Yanglao (SI 6), Jingming (BL 1) and Cuanzhu (BL 2) in the thumb-tack needle group, 2 times a week. In the western medication group, 0.1% sodium hyaluronate eye drops were applied, 3 times a day. Both groups were treated for 4 weeks. Before and after treatment, TCM symptom score, tear film break-up time (BUT), SchirmerⅠtest (SⅠT), corneal fluorescein sodium staining (FL) score and 36-item short form health survey (SF-36) score were observed, and the clinical efficacy was evaluated in the two groups. RESULTS: After treatment, the total scores and each item score of TCM symptom in the two groups were decreased compared with before treatment (P<0.05); except for score of visual fatigue and photophobia, the total score and each item score of TCM symptom in the thumb-tack needle group were lower than the western medication group (P<0.05). After treatment, the BUT, SⅠT and SF-36 scores were increased and the FL scores were decreased in the two groups (P<0.05); the BUT, SⅠT and SF-36 score were higher than the western medication group (P<0.05), and the FL score was lower than the western medication group (P<0.05) in the thumb-tack needle group. The total effective rate in the thumb-tack needle group was 93.3% (28/30), which was higher than 80.0% (24/30) in the western medication group (P<0.05). CONCLUSION: Thumb-tack needle based on Biaoben Genjie theory could effectively relieve clinical symptoms of dry eye patients, prolong tear film break-up time, increase tear secretion, improve tear film function and quality of life, and its curative effect is better than sodium hyaluronate eye drops.

GenOrigin: A comprehensive protein-coding gene origination database on the evolutionary timescale of life.

The origination of new genes contributes to the biological diversity of life. New genes may quickly build their network, exert important functions, and generate novel phenotypes. Dating gene age and inferring the origination mechanisms of new genes, like primate-specific genes, is the basis for the functional study of the genes. However, no comprehensive resource of gene age estimates across species is available. Here, we systematically date the age of 9,102,113 protein-coding genes from 565 species in the Ensembl and Ensembl Genomes databases, including 82 bacteria, 57 protists, 134 fungi, 58 plants, 56 metazoa, and 178 vertebrates, using a protein-family-based pipeline with Wagner parsimony algorithm. We also collect gene age estimate data from other studies and uniformly distribute the gene age estimates to time ranges in a million years for comparison across studies. All the data are cataloged into GenOrigin (http://genorigin.chenzxlab.cn/), a user-friendly new database of gene age estimates, where users can browse gene age estimates by species, age, and gene ontology. In GenOrigin, the information such as gene age estimates, annotation, gene ontology, ortholog, and paralog, as well as detailed gene presence/absence views for gene age inference based on the species tree with evolutionary timescale, is provided to researchers for exploring gene functions.

Bioactive phenylpropanoid derivatives from the fruits of Lycium ruthenicum Murr.

Eight new (1-7 and 15) and 18 known (8-14 and 16-26) phenylpropanoid derivatives were isolated from the fruits of Lycium ruthenicum Murr. (black wolfberry). Their structures were determined by comprehensive spectroscopic analyses, chemical methods, and comparisons of spectroscopic data. Four known compounds (16, 17, 24, and 26) were firstly isolated from the genus Lycium. Interestingly, compounds 1/2 and 4/5 were isolated as two pairs of inseparable anomers owing to the tautomerism of the free hemiacetal at C-1'' in solution. The antioxidant, α-glucosidase inhibitory, and acetylcholinesterase (AChE) inhibitory activities of compounds 1-26 were evaluated. Some compounds possessed DPPH radical scavenging activity, and all compounds (1-26) exhibited different levels of oxygen radical absorbance capacity (ORAC). One compound displayed α-glucosidase inhibitory activity with potency close to that of the positive control (acarbose).

Cycloartane-type triterpenoids from the root of Astragalus membranaceus var. mongholicus.

Three new (1-3) and 11 known (4-14) cycloartane-type triterpenoids were isolated from the root of Astragalus membranaceus var. mongholicus. Their structures were determined by spectroscopic analyses and chemical methods. Cycloartane-type triterpenoids are a class of major bioactive constituents in the root of A. membranaceus var. mongholicus, and the discovery of compounds 1-3 added new members of this kind of natural product. [Formula: see text].

pyMeSHSim: an integrative python package for biomedical named entity recognition, normalization, and comparison of MeSH terms.

BACKGROUND: Many disease causing genes have been identified through different methods, but there have been no uniform annotations of biomedical named entity (bio-NE) of the disease phenotypes of these genes yet. Furthermore, semantic similarity comparison between two bio-NE annotations has become important for data integration or system genetics analysis. RESULTS: The package pyMeSHSim recognizes bio-NEs by using MetaMap which produces Unified Medical Language System (UMLS) concepts in natural language process. To map the UMLS concepts to Medical Subject Headings (MeSH), pyMeSHSim is embedded with a house-made dataset containing the main headings (MHs), supplementary concept records (SCRs), and their relations in MeSH. Based on the dataset, pyMeSHSim implemented four information content (IC)-based algorithms and one graph-based algorithm to measure the semantic similarity between two MeSH terms. To evaluate its performance, we used pyMeSHSim to parse OMIM and GWAS phenotypes. The pyMeSHSim introduced SCRs and the curation strategy of non-MeSH-synonymous UMLS concepts, which improved the performance of pyMeSHSim in the recognition of OMIM phenotypes. In the curation of 461 GWAS phenotypes, pyMeSHSim showed recall > 0.94, precision > 0.56, and F1 > 0.70, demonstrating better performance than the state-of-the-art tools DNorm and TaggerOne in recognizing MeSH terms from short biomedical phrases. The semantic similarity in MeSH terms recognized by pyMeSHSim and the previous manual work was calculated by pyMeSHSim and another semantic analysis tool meshes, respectively. The result indicated that the correlation of semantic similarity analysed by two tools reached as high as 0.89-0.99. CONCLUSIONS: The integrative MeSH tool pyMeSHSim embedded with the MeSH MHs and SCRs realized the bio-NE recognition, normalization, and comparison in biomedical text-mining.

Anti-masculinization induced by aromatase inhibitors in adult female zebrafish.

BACKGROUND: Early sex differentiation genes of zebrafish remain an unsolved mystery due to the difficulty to distinguish the sex of juvenile zebrafish. However, aromatase inhibitors (AIs) could direct juvenile zebrafish sex differentiation to male and even induce ovary-to-testis reversal in adult zebrafish. RESULTS: In order to determine the transcriptomic changes of sex differentiation in juvenile zebrafish and early sex-reversal in adult zebrafish, we sequenced the transcriptomes of juvenile and adult zebrafish treated with AI exemestane (EM) for 32 days, when juvenile zebrafish sex differentiation finished. EM treatment in females up-regulated the expression of genes involved in estrogen metabolic process, female gamete generation and oogenesis, including gsdf, macf1a and paqr5a, while down-regulated the expression of vitellogenin (vtg) genes, including vtg6, vtg2, vtg4, and vtg7 due to the lower level of Estradiol (E2). Furthermore, EM-juveniles showed up-regulation in genes related to cell death and apoptosis, such as bcl2l16 and anax1c, while the control-juveniles exhibited up-regulation of genes involved in positive regulation of reproductive process and oocyte differentiation such as zar1 and zpcx. Moreover, EM-females showed higher enrichment than control females in genes involved in VEGF signaling pathway, glycosaminoglycan degradation, hedgehog signaling pathway, GnRH signaling pathway and steroid hormone biosynthesis. CONCLUSIONS: Our study shows anti-masculinization in EM-treated adult females but not in EM-treated juveniles. This may be responsible for the lower sex plasticity in adults than juveniles.

A new diterpenoid alkaloid from Aconitum hemsleyanum.

A new C19-diterpenoid alkaloid named hemsleyaline (1), along with fourteen known alkaloids (2-15), were isolated from the roots of Aconitum hemsleyanum Pritz. (Ranunculaceae), a herbal medicine in southwest China. Their structures were established on the basis of extensive spectroscopic analyses. Compound 1 showed mild cholinesterase inhibitory effect with IC50 value of 471 ± 9 µM.