Aim To identify the molecular target of gabapentin in the treatment of postherpetic neuralgia(PHN). Methods The molecular target of gabapentin for PHN was analyzed by network pharmacology and molecular docking and confirmed by coprecipitation test. Rats were randomly divided into control group, model group, model+50 mg·kg-1 gabapentin group, model+100 mg·kg-1 gabapentin group, and model+200 mg·kg-1 gabapentin group, with nine rats in each group. The pain-related behaviors of the rats were measured at different time points. The mRNA and protein expressions of CACNA2D1, Bax, and Bcl-2 in rat spinal cord were determined by immunofluorescence, Western blot, and qPCR. Results CACNA2D1 was the target gene of gabapentin that determined via network pharmacology, molecular docking, and co-precipitation tests. After modeling, mechanical pain threshold and thermal pain threshold significantly decreased, and the number of apoptotic GABA cells significantly increased. However, after intraperitoneal injection of 50, 100, and 200 mg·kg-1 gabapentin, mechanical pain threshold and thermal pain threshold significantly increased(P<0.05), and the number of apoptotic GABA cells significantly decreased(P<0.01). Immunofluorescence and Western blot results showed that compared with the model group, with the increase of gabapentin concentration, the positive expression rate of Bax significantly decreased, and the positive expression rate of Bcl-2 and CACNA2D1 significantly increased. The mRNA expression levels of Bax, Bcl-2 and CACNA2D1 detected by qPCR were consistent with the results of immunofluorescence and Western blot. Conclusions Gabapentin up-regulates the expression of target protein CACNA2D1, inhibits the proapoptotic protein Bax, and promotes the expression of apoptotic inhibitor Bcl-2.

Objective To explore the potential targets of triclosan in the treatment of nonalcoholic fatty liver disease(NAFLD) and to provide new clues for the future research on the application of triclosan. Methods The targets of triclosan and NAFLD were obtained via network pharmacology.The protein-protein interaction network was constructed with the common targets shared by triclosan and NAFLD.The affinity of triclosan to targets was verified through molecular docking.Gene ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were carried out to analyze the key targets and the potential mechanism of action.NAFLD model was established by feeding male C57BL/6J mice with high-fat diet for 12 weeks.The mice were randomly assigned into a model group and a triclosan group [400 mg/(kg·d),gavage once a day for 8 weeks].The hematoxylin-eosin(HE) staining was used for observation of the pathological changes and oil red O staining for observation of fat deposition in mouse liver.Western blotting was employed to detect the protein level of peroxisome proliferator-activated receptor alpha(PPARα) in the liver tissue. Results Triclosan and NAFLD had 34 common targets,19 of which may be the potential targets for the treatment,including albumin(ALB),PPARα,mitogen-activated protein kinase 8(MAPK8),and fatty acid synthase.Molecular docking predicted that ALB,PPARα,and MAPK8 had good binding ability to triclosan.KEGG pathway enrichment showcased that the targets were mainly enriched in peroxisome proliferator-activated receptor signaling pathway,in which ALB and MAPK8 were not involved.Triclosan alleviated the balloon-like change and lipid droplet vacuole,decreased the lipid droplet area,and up-regulated the expression level of PPARα in mouse liver tissue. Conclusion PPARα is a key target of triclosan in the treatment of NAFLD,which may be involved in fatty acid oxidation through the peroxisome proliferator activated receptor signaling pathway.
Animals ; Liver/pathology* ; Male ; Mice ; Mice, Inbred C57BL ; Molecular Docking Simulation ; Network Pharmacology ; Non-alcoholic Fatty Liver Disease/drug therapy* ; PPAR alpha/therapeutic use* ; Triclosan/therapeutic use*

Objective: To investigate the distribution of HIV-1 genetic subtypes and pretreatment drug resistance (PDR) among men who have sex with men (MSM) from 19 cities of 6 provinces in China. Methods: From April to November 2019, 574 plasma samples of ART-naive HIV-1 infected MSM were collected from 19 cities in Hebei, Shandong, Jiangsu, Zhejiang, Fujian, and Guangdong provinces, total ribonucleic acid (RNA) was extracted and amplified the HIV-1 pol gene region by nested polymerase chain reaction (PCR) after reverse transcription. Then sequences were used to construct a phylogenetic tree to determine genetic subtypes and submitted to the Stanford drug resistance database for drug resistance analysis. Results: A total of 479 samples were successfully amplified by PCR. The HIV-1 genetic subtypes included CRF01_AE, CRF07_BC, B, CRF55_01B, CRF59_01B, CRF65_cpx, CRF103_01B, CRF67_01B, CRF68_01B and unrecognized subtype, which accounted for 43.4%, 36.3%, 6.3%, 5.9%, 0.8%, 0.8%, 0.4%, 0.4%, 0.2% and 5.5%, respectively. The distribution of genetic subtypes among provinces is statistically different (χ²=44.141, P<0.001). The overall PDR rate was 4.6% (22/479), the drug resistance rate of non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors were 3.5% (17/479), 0.8% (4/479) and 0.2% (1/479), respectively. The PDR rate of recent infections was significantly higher than that of long-term infections (χ²=4.634, P=0.031). Conclusions: The HIV-1 genetic subtypes among MSM infected with HIV-1 from 19 cities of 6 provinces in China are diverse, and the distribution of subtypes is different among provinces. The overall PDR rate is low, while the PDR rate of recent infections was significantly higher than that of long-term infections, suggesting the surveillance of PDR in recent infections should be strengthened.
China/epidemiology* ; Cities ; Drug Resistance ; Drug Resistance, Viral/genetics* ; Female ; Genotype ; HIV Infections/epidemiology* ; HIV Seropositivity/drug therapy* ; HIV-1/genetics* ; Homosexuality, Male ; Humans ; Male ; Phylogeny ; Reverse Transcriptase Inhibitors/therapeutic use* ; Sexual and Gender Minorities

Antibodies, Viral ; blood ; Betacoronavirus ; Coronavirus ; immunology ; Coronavirus Infections ; immunology ; Humans ; Immunoglobulin G ; blood ; Pandemics ; Pneumonia, Viral ; immunology

Objective: To reveal the related factors of inhibitors and differences ofhemorrhage and joint disease before and after the production of inhibitors in children with hemophilia A (HA) . Methods: Retrospective analyses of the clinical data of 381 children with HA under the age of 16 registered in the Registration Management Center of Hemophilia in Henan Provincial from January 2015 to August 2018. Results: A total of the 381 children were enrolled with 116 (30.4%) mild, 196 (51.4%) moderate, and 69 (18.1%) severe cases; 54 patients (14.2%) had inhibitors, including 22 high and 32 low titer inhibitors. Positive family history was positively associated with inhibitors[P<0.001, OR=3.299 (95%CI 1.743-5.983) ], and high-intensity exposure was associated with inhibitors[P=0.002, OR=2.587 (95%CI 1.414-4.731) ]. High-intensity exposure was associated with high titer inhibitor production[P=0.001, OR=8.689 (95%CI 2.464-30.638) ], and high-intensity exposure increased the risk of high titer inhibitors in HA patients. After inhibitors occurred in 54 patients with HA, the rates of overall joint annual bleeding (z=-3.440, P=0.001) and traumatic annual bleeding (z=-2.232, P=0.026) increased, but the rates of the annual joint bleeding (z=-1.342, P=0.180) and spontaneous annual bleeding (z=-1.414, P=0.157) remained to be not statistically significant. The joint ultrasound score did not change significantly after the inhibitor information (z=-0.632, P=0.527) . Conclusions: Positive family history and high-intensity exposure could increase the risk of F Ⅷ inhibitors in HA patients, and high-intensity exposure increased the risk of high titer inhibitors. The rates of the overall joint annual bleeding and traumatic annual bleeding increased after the inhibitor information.
Child ; Factor VIII/therapeutic use* ; Hemarthrosis ; Hemophilia A/drug therapy* ; Hemorrhage ; Humans ; Retrospective Studies

OBJECTIVETo investigate the effects of rhubarb powder on serum complement 3 (C3), complement 4 (C4), and hypersensitive C-reactive protein (hs-CRP) levels in patients with hypertensive intracerebral hemorrhage (HICH) after operation.

METHODSForty inpatients with HICH after operation were recruited from Department of Cerebral Surgery, Affiliated Hospital of Shaanxi College of Traditional Chinese Medicine from July 2009 to March 2010. They were randomly assigned to the treatment group (20 cases) and the control group (20 cases). From the 4th day after surgery, all patients received routine Western medical treatment. The rhubarb powder, 5-10 g dissolving in 40 mL warm water, was administered or nasally fed to those in the treatment group, 2 -3 times daily for 10 successive days. The contents of serum C3, C4, and hs-CRP were detected in the two groups on the 7th day and the 14th day after operation. The serum hs-CRP content was detected using latex particle enhanced immunoturbidimetric assay. The Scandinavia Stroke Scale (SSS) scores were recorded in the two groups.

RESULTSCompared with the same group on the 4th day after operation, the levels of serum C3 and C4 increased on the 7th day after operation, and SSS score increased on the 14th day after operation in the control group (P < 0.05). The contents of C4 and hs-CRP decreased, and the SSS score increased on the 14th day after operation in the treatment group (P < 0.05). Compared with the same group on the 7th day after operation, the contents of C4 and hs-CRP decreased and the SSS score increased on the 14th day after operation in the treatment group (P < 0.05). Compared with the control group at the same time points, the contents of C4 and C3 decreased on the 7th day after operation; the contents of C3, C4, and hs-CRP decreased, and SSS score increased in the treatment group on the 14th day after operation (P < 0.05).

CONCLUSIONThe rhubarb powder could significantly decrease the serum levels of C3, C4, and hs-CRP, and improve the curative effect in patients with HICH after operation.

Adult ; C-Reactive Protein ; metabolism ; Cerebral Hemorrhage ; blood ; Complement C3 ; metabolism ; Complement C4 ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Female ; Humans ; Male ; Middle Aged ; Postoperative Period ; Rheum ; chemistry

OBJECTIVETo evaluate the diagnostic value and safety of percutaneous lung biopsy in hematologic patients with lung infection.

METHODS28 cases hematologic patients received CT-guided percutaneous lung biopsy when they developed a fever associated with pulmonary nodules or lumps in CT scan whose clinical diagnosis were unclear during or after chemotherapy. Sample of each lesion were drawn twice. The lung tissue was re-scanned after lung biopsy to check up in order to discover bleeding and pneumothorax. Biopsy tissue was examined by bacteria culture, acid-fast staining and pathology. Pathological examination contained HE staining, acid-fast stain, PAS stain, TB-DNA, methenamine silver and others.

RESULTS28 cases contain 24 males and 4 females. Median age was 40 15 - 77 years old. Blood tests were as follows: 3 cases with HGB > 110 g/L, 9 with HGB 90 - 110 g/L, 12 with HGB 60 - 89 g/L, 4 with HGB < 60 g/L. 8 with WBC > 10×10(9)/L, 6 with WBC (4 - 10)×10(9)/L, 13 with WBC < 4×10(9)/L, 1 with WBC < 2×10(9)/L; 14 with PLT > 100×10(9)/L, 5 with PLT (50 - 100)×10(9)/L, 5 with PLT < 50×10(9)/L, 4 with PLT < 30×10(9)/L. 4 cases had mild extended PT, 3 mild extended APTT, 3 FIB lower than normal. Lung CT scans were as follows: 4 cases with simply lesion in right lung, 4 with simply lesion in left lung, 20 with lesions in bilateral lung. 8 cases were diagnosed as fungal infection, 3 as tuberculosis infection, 1 as lung cancer, 1 as pulmonary infiltration of lymphoma, 1 as pulmonary infiltration of leukemia, and 14 as inflammatory changes with no specific diagnosis. 4 cases came with pneumothorax during lung biopsy, mild to moderate in 3 cases and severe in 1 case. Severe patient turned better after CT-guided suction. 3 cases with mild hemoptysis turned better after treatment.

CONCLUSIONWhen hematopathy patients are with pulmonary nodules or lumps in CT scan whose clinical diagnosis is unclear, CT-guided percutaneous lung biopsy is safe and conducive to early diagnosis and conducive to early rehabilitation of patients if the coagulation function is basically normal and platelet count is not too low.

Adolescent ; Adult ; Aged ; Biopsy ; Female ; Hematologic Diseases ; microbiology ; pathology ; Humans ; Lung ; pathology ; Male ; Middle Aged ; Pneumonia ; diagnosis ; Young Adult

OBJECTIVETo explore the effect and mechanism of DNA polymerase β expression level on cell apoptosis and mitochondrial membrane potential induced by hydroquinone.

METHODSPolβ wild-type cells (polβ+/+), polβ overexpressed cells (polβ oe) and polβ null cells (polβ-/-) were applied as a model cell system, The effect of cell apoptosis and mitochondrial membrane potential induced by different doses of hydroquinone were analyzed by flow cytometry. The ROS and ·OH assay kit were used to examine the cellular ROS and ·OH level. The activity of cellular SOD and GSH-Px were tested by Chemiluminescence method after exposed to different concentrations of hydroquinone.

RESULTSWith the dose of hydroquinone increased, the rate of apoptosis and falling of mitochondrial membrane potential (ΔΨm) in cells were increased compared with the control. When compared with polβ+/+ cells, the rate of apoptosis in polβ-/- cells exposed to 20.00, 40.00, 80.00 µmol/L hydroquinone increased and the rate of apoptosis in polβ oe cells exposed to 10.00, 20.00, 40.00, 80.00 µmol/L hydroquinone decreased (P < 0.05). Compared with polβ+/+ cells (20.60% ± 0.57%, 37.95% ± 0.64%, 44.50% ± 1.27%, 57.55% ± 1.06%), the rate of cell which undergone mitochondrial depolarization in polβ-/- cells treated with 10.00, 20.00, 40.00, 80.00 µmol/L hydroquinone (33.60% ± 1.55%, 46.05% ± 1.77%, 52.75% ± 2.05%, 75.20% ± 0.56%) increased. The rate of cell which undergone mitochondrial depolarization in polβ oe cells exposed to 10.00, 20.00, 40.00, 80.00 µmol/L hydroquinone (16.05% ± 1.20%, 29.80% ± 1.21%, 35.15% ± 1.06%, 53.80% ± 0.85%) decreased (P < 0.05). When compared with polβ+/+ cells, fluorescent intensity of polβ-/- cells treated with different dosages of hydroquinone increased, while which of polβ oe cells decreased (P < 0.05). Compared with polβ+/+ cells, ·OH level of polβ-/- cells treated with 20.00, 40.00 µmol/L hydroquinone significantly enhanced, while which of polβ oe cells decreased sharply (P < 0.05). Under the same concentrations of hydroquinone, the activity of SOD and GSH-Px were decreased most rapidly in polβ-/- cells. The activity of SOD and GSH-Px in polβ oe cells decreased slower than in the polβ-/- cells.

CONCLUSIONHydroquinone could induced apoptosis by the generation of ROS and decrease of ΔΨm; polβ could protect cells from apoptosis induced by hydroquinone through decrease of ROS level and depolarization of mitochondria.

Animals ; Apoptosis ; drug effects ; Cells, Cultured ; DNA Polymerase beta ; metabolism ; Hydroquinones ; toxicity ; Membrane Potential, Mitochondrial ; drug effects ; Mice

OBJECTIVETo explore the effects of DNA polymerase β expression level on the genotoxicity and genetic instability induced by benzo(a)pyrene (BaP),and provide experimental the basis for further study on the carcinogenic molecular mechanism of BaP.

METHODSThree kinds of cell lines with the identical genetic background, polβ wild-type cells (polβ+/+), polβ null cells (polβ-/-) and polβ overexpression cells (polβ oe) were applied as cellular models. The oxidative damage, genotoxicity and genetic instability induced by BaP were analyzed by using different methods respectively.

RESULTSCell viability and colony forming ability of 3 kinds of cell lines exposed to BaP decreased with BaP. After treated with 5 and 20 µmol/L concentration of BaP, fluorescence intensity of polβ-/- cell line was significantly higher than that of other two cell lines (P < 0.05). When treated with 5.00 µmol/L and 20.00 µmol/L concentration of BaP, the SOD activities (76.56 ± 2.84 and 62.78 ± 4.28 U/mg pro) of polβ-/- cell line were significantly lower than that (84.85 ± 3.59) of control group and those (85.21 ± 3.20 and 76.90 ± 3.38 U/mg pro) of polβ+/+ cell line. In 20.00 µmol/L BaP group. SOD activity (82.59 ± 4.64 U/mg pro) of polβ oe cell line was lower than that (88.58 ± 6.77 U/mg pro) of control but higher than that of polβ+/+ cell line (P < 0.05). In 1.25, 5.00 and 20.00 µmol/L concentration BaP groups, the micronucleus rates of polβ-/- cell line were much higher than those of polβ+/+ cell line (P < 0.05). In 5.00 and 20.00 µmol/L concentration BaP groups, the micronucleus rates of polβ oe cell line were significantly lower than those of polβ+/+ line (P < 0.05). In 5.00 and 20.00 µmol/L concentration BaP groups, HPRT gene mutation frequencies (26.16 × 10(-6) and 37.51 × 10(-6); 27.68 × 10(-6) and 38.63 × 10(-6)) in polβ-/- cells and polβ oe cells were significantly higher than those (19.76 × 10(-6) and 24.78 × 10(-6)) of polβ+/+ cells (P < 0.05).

CONCLUSIONPolβ could play a role in protecting the cells from the genotoxicity and genetic instability induced by BaP, and the normal expression level of polβ was indispensable for maintaining genome stability.

Animals ; Benzo(a)pyrene ; toxicity ; Cell Line ; DNA Damage ; DNA Polymerase beta ; metabolism ; Mice ; Micronucleus Tests ; Mutation Rate