Abstract: Objective　By analyzing the frequency distribution of antihypertensive drug-related genotypes in hypertensionpatients treated in our hospital, so as to provide a clinical basis for individualized treatment of hypertension patients. Methods　A total of 72 hypertensive patients treated in Hainan Hospital of PLA General Hospital from June 2021 to April 2022 were collected. PCR-melting curve method was used to detect CYP2D6*10 (c.100 C>T), CYP2C9*3 (c.1075 A>C), ADRB1 (c.1165 G>C), AGTR1 (c.1166 A>C), ACE (I/D), NPPA (T2238C) and CYP3A5*3 (A6986G), and the relationship between different genotypes and biochemical indexes was analyzed. Results　According to the statistics of the gene and genotype frequency of each point in 72 patients, the gene frequencies of 7 sites all conformed to Hardy Weinberg equilibrium. There were gender differences in ADRB1 genotypes (χ2 = 5.878, P<0.05). There were statistical differences in triglycerides [AA: 1.4 (1.0, 2.0)mmol/L; AC: 2.2 (1.5, 2.5)mmol/L; P=0.038], total cholesterol [AA: 4.0 (3.1, 4.9) mmol/L; AC: 4.8 (4.0, 5.3) mmol/L; P=0.040] and low-density lipoprotein cholesterol [(AA: 2.4 (1.8, 3.3) mmol/L; AC: 3.2 (2.5, 3.5) mmol/L; P=0.035] among patients with different genotypes of AGTR1 locus. The patients with different genotypes of CYP2C9 locus had significant differences in their alanine transferase (ALT) [AA:16.9 (11.4,30.2) mmol/L; AC:10.4 (9.4, 18.2) mmol/L; P=0.040]. Aftergene-directed individualized therapy, different genotypes of CYP3A5 andAGTR1 affected the heart rate [CYP3A5: AA: (79.3±7.0) beats/min; AG： (69.8±6.8) beats/min; GG： (68.8±7.3) beats/min; P=0.010], systolic blood pressure [AGTR1: AA: (131.3±16.7) mmHg; AC: (140.6±11.8) mmHg; P=0.014] and diastolic blood pressure [CYP3A5: AA: (90.0±8.3) mmHg; AG: (78.7±10.8) mmHg; GG: (74.9±10.7) mmHg; P=0.025; AGTR1: AA: (75.3±10.2) mmHg; AC: (86.3±10.6) mmHg; P=0.001] of patients. Conclusions　The related gene loci of antihypertensive drugs are an important basis for guiding the diversification and individualization of clinical medication. Clinicians need to consider the impact of related genes on drug efficacy and adverse reactions when prescribing.

AIM:To explore the potentially beneficial clinical effects of traditional Chinese medicine(TCM) combined with photocoagulation for diabetic retinopathy(DR).METHODS:Chinese patients with DR were divided into two groups. A joint treatment group received both the TCM ziyinliangxuesanyutang and photocoagulation, while a control group received only photocoagulation laser treatment. Visual acuity tests, visual field retinal sensitivity tests, and fundus fluorescein angiography (to measure neovascular regression) were performed. Vision was compared between the two groups 1 month, 6, and 12 months after treatment.RESULTS:Twelve months after treatment, the recovery of visual acuity (62.3% vs 43.1%, P=0.037) and retinal sensitivity \[17.0±3.7 decibels (dB) vs 14.9±3.7dB, P=0.002\] as well as neovascular regression (67.2% vs 48.3%, P=0.036) in the joint treatment group were all significantly greater than that of the control group.CONCLUSION:Compared with laser treatment alone, the joint application of TCM and photocoagulation is shown to be more effective than DR treatment method.

OBJECTIVETo explore the effects of different liquid therapies on the intracranial pressure, brain water content, and expressions of aquaporin-4 and N-methyl-D-aspartate-1 in the brain tissue.

METHODSTwo intervention factors including the colloids (two levels: 4% gelofusine; 6% hydroxyethyl starch and sodium chloride injection) and the crystal/gel ratios (two levels: 0:1; 1:1) were set based on the results of the analysis of variance of factorial design. Thirty-two patient who had undergone epilepsy surgery were equally and randomly divided into four groups: group A (4% gelofusine, crystal/gel ratio 0:1); group B (6% hydroxyethyl starch and sodium chloride injection, crystal/gel ratio 0:1); group C (4% gelofusine, crystal/gel ratio 1:1); and group D (6% hydroxyethyl starch and sodium chloride injection, crystal/gel ratio 1:1). The intracranial pressure during operation was recorded. After the operation, the intracranial pressure and brain water content were measured and the expressions of aquaporin-4 and N-methyl-D-aspartate-1 in the brain tissue were determined with Western blot. Glasgow coma scores were obtained 2 hours after operation.

RESULTSThe intracranial pressure (F=55.714, P=0.000; F=142.432, P=0.000) and the brain water content (F=31.477, P=0.000; F=84.896, P=0.000) significantly increased after the application of the 6% hydroxyethyl starch and sodium chloride injection and crystal/gel ratio 1:1, and the expressions of aquaporin-4 (F=37.205, P=0.000; F=149.652, P=0.014) and N-methyl-D-aspartate-1(F=29.664, P=0.000; F=65.951, P=0.000) in the brain tissue significantly increased. There were additive effects between two of them (the intracranial pressure: F=11.056, P=0.002; the brain water content: F=8.007, P=0.008; the expression of aquaporin-4: F=9.845, P=0.004; and the expression of N-methyl-D-aspartate-1: F=5.020, P=0.033). However, the Glasgow coma score showed no significant difference after the administration (P>0.05).

CONCLUSIONThe liquid therapy with 4% gelofusine and crystal/gel ratio 0:1 can result in better control on the intracranial pressure, brain water content and expressions of aquaporin-4 and N-methyl-D-aspartate-1 in the brain tissue better than the liquid therapy with 6% hydroxyethyl starch and crystal/gel ratio 1:1 during neurosurgery, although it may not improve the coma status.

Adolescent ; Adult ; Aquaporin 4 ; metabolism ; Brain ; drug effects ; metabolism ; Female ; Fluid Therapy ; methods ; Humans ; Intracranial Pressure ; drug effects ; Male ; Middle Aged ; N-Methylaspartate ; metabolism ; Water ; metabolism ; Young Adult

BACKGROUNDIn this prospective randomized study, we compared the predicted blood and effect-site C 50 for propofol and remifentanil target-controlled infusion (TCI) and the bispectral index (BIS) values at loss of consciousness (LOC) and response to a standard noxious painful stimulus (LOS) in elderly and young patients, respectively. We hypothesized that the elderly patients will require lower target concentration of both propofol and remifentanil at above two clinical end-points.

METHODSThere were 80 American Society of Anesthesiologists (ASA) physical status I-II unpremedicated patients enrolled in this study, they were divided into elderly group (age ≥65 years, n = 40) and young group (aged 18-64 years, n = 40). Propofol was initially given to a predicted blood concentration of 1.2 μg/ml and thereafter increased by 0.3 μg/ml every 30 s until Observer's Assessment of Alertness and Sedation score was 1. The propofol level was kept constant, and remifentanil was given to provide a predict blood concentration of 2.0 ng/ml, and then increased by 0.3 ng/ml every 30 s until loss of response to a tetanic stimulus. BIS (version 3.22, BIS Quattro sensor) was also recorded.

RESULTSIn elderly group, the propofol effect-site C 50 at LOC of was 1.5 (1.4-1.6) μg/ml, was significantly lower than that of young group, which was 2.2 (2.1-2.3) μg/ml, the remifentanil effect-site C 50 at LOS was 3.5 (3.3-3.7) ng/ml in elderly patients, was similar with 3.7 (3.6-3.8) ng/ml in young patients. Fifty percent of patients lost consciousness at a BIS value of 57.3 (56.4-58.1), was similar with that of young group, which was 55.2 (54.0-56.3).

CONCLUSIONIn elderly patients, the predicted blood and effect-site concentrations of propofol at LOC were lower than that of young patients. At same sedation status, predicted blood and effect-site concentrations of remifentanil required at LOS were similar in elderly and young patients. BIS were not affected by age. Low-propofol/high-opioid may be optional TCI strategy for elderly patients.

Adolescent ; Adult ; Age Factors ; Aged ; Anesthetics, Intravenous ; administration & dosage ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Piperidines ; administration & dosage ; therapeutic use ; Propofol ; administration & dosage ; therapeutic use ; Prospective Studies ; Unconsciousness ; chemically induced ; Young Adult

Adhesives ; chemistry ; Benzene ; analysis ; Chromatography, Gas ; Hexanes ; analysis ; Toluene ; analysis ; Trichloroethylene ; analysis

Objective To investigate the click and tone burst evoked auditory brainstem responses (ABR)in normal Wistar rat,and to establish the standards of ABR testing method,and to provide a reference for studies rat audition.Methods Fifteen male Wistar rats(30 ears)were used in this sutdy.The latency and amplitude of ABR e-voked by click and TB at 80,50 and 20 dB SPL were measured.Results The occurrence rate of wave Ⅱand Ⅳat low levels(20 dB SPL)was nearly the same according to the amplitude.The cABR (dB peSPL)threshold was 21.83± 4.45 and tbABR (dB SPL)thresholds were 2.02±0.09,2.88±0.16,3.77±0.25,4.69±0.29,and 5.78±0.41, respectively.80 dB stimulus evoked cABR (peSPL)wave I,I b,II,III,IV and V latency (ms)were 1.76±0.12, 2.13±0.11,2.67±0.16,3.49±0.28,4.39±0.29,and 5.45±0.41,respectively.tbABR (SPL)of wave I,Ib, II,III,IV and V latency (ms)at 4 kHz were 2.02±0.09,2.88±0.16,3.77±0.25,4.69±0.29,and 5.78± 0.41,respectively.At 8 kHz they were 1.76±0.07,2.28±0.10,2.63±0.16,3.49±0.21,4.44±0.28,and 5.48±0.43;while at 12 kHz were1.76±0.08,2.24±0.12,2.61±0.25,3.53±0.25,4.46±0.32,and 5.52± 0.45;at 16 kHz were 1.79±0.10,2.25±0.12,2.70±0.18,3.62±0.27,4.52±0.37,and 5.61±0.49;at 24 kHz were 1.75±0.09,2.27±0.11,2.67±0.16,3.60±0.27,4.52±0.38,and 5.60±0.51;at 32 kHz were 1.77±0.10,2.24±0.12,2.64±0.20,3.59±0.34,4.52±0.40,and 5.61±0.52,respectively.Conclusion Wave Ⅳ was the best wave to determine threshold of click and tone burst evoked auditory brainstem response in rat.

OBJECTIVETo explore highly agglutinative staphylococcin (HAS) pomoting on tendon-bone healing after reconstruction of anterior cruciate ligament(ACL) in rabbits.

METHODSAnimal model of ACL reconstruction in 24 mature New Zealand white rabbits(3 months, 2.56 kg on average, either gender) were established using autologous digital long extensor tendon and randomly classified into 2 groups(HAS and control group), 12 rabbits for each group. HAS group was separately injected 0.1ml highly agglutinative staphylococcin immediately into tendon-bone interface during the operation and 2 days after operation. Control group was injected with the same dose of physiological saline for 3 days. All animals were sacrificed at 4, 8, and 12 weeks after operation for histological examinations. The specimens were stained with hematoxylin-eosin, picric acid-sirius red, VEGF immunohistochemistry stain, and toluidine blue to histologically analysis the total pathology changes of the tendon-bone healing tissue, the tendon bone interface morphology classification, hyperplasia and arrangement of collagen fiber, vascularization and new bone formation, respectively.

RESULTSThe Yamakado morphological interface results showed that the tissue healing at tendon-bone interface of the HAS group was better than that of the control group. The histological examination revealed that on the 4th week after operation, the tendon-bone interface of HAS group was filled with fibrous connective tissue. The proliferated fibroblasts, chondroblasts and the angiogenesis were rich. On the 8th week after operation, the healing tissue at the bone-tendon interface had developed into dense connective tissue, the neo-vessels were very rich, the collagen fibers were formed abundantly, some Sharpey's fibers spanning parts of the tendon-bone interface. On the 12th week after operation, the transition zones were full of Sharpey's fibers;the neo-vessels were not as much as the 8th weeks, but new bone formation was further increased and immature fibrocartilage appeared. For quantitative histological analysis at 4, 8 and 12 weeks after operation, the proportion of neo-vessel area and the area of now bone formation of the HAS group were all significantly higher than those of the control group(<0.05).

CONCLUSIONSUnder the synergy of staphylococcal enterotoxin C and other active ingredients, Highly Agglutinative Staphylococcin can significantly improve the tendon-bone healing after ACL reconstruction in rabbit knees, which is expected to be a new method to improve the clinical results of ACL reconstruction.

BACKGROUNDThe present study was undertaken to replicate the associations of representative polymorphisms in three genes (complement factor H (CFH), complement factor B (BF) and HtrA serine peptidase 1 (HTRA1)) with exudative age-related macular degeneration (AMD) in a Han Chinese population, and to test if the modifiable environmental factors affect AMD susceptibility associated with different type of genotype in these genes.

METHODSAn age, gender and ethnicity matched case-control study was conducted to genotype the representative single neucleotide polymorphisms (SNPs) loci including rs1061170 and rs1410996 in CFH, rs641153 and rs4151667 in BF and rs11200638 in HTRA1 gene in 144 exudative AMD patients and 126 normal controls using PCR-RFLP and direct resequencing. The demographic characteristics and behavioral risk factors were also recorded. Allelic and genotypic associations for individual SNP and joint associations with two loci were performed. The gene-gene and gene-environment interactions were analyzed using multivariate non-conditional Logistic regression analysis.

RESULTSThe C risk allele frequencies for CFH Y402H (rs1061170) in cases and controls were 12.5% and 5.4% respectively, which were much lower than those in Caucasians (P < 0.001). Compared with TT homozygous genotype, the CT heterozygous genotype was positively associated with AMD with odds ratio (OR) of 3.23 (1.36 - 5.07). However, the population attributable risk (PAR) of C allele was only 3.3% (1.4% - 4.3%). rs1410996 was also associated with AMD independent of Y402H. The ORs of exudative AMD for individuals carrying one copy risk allele and two copy risk alleles were 2.57 (1.21 - 5.45) and 4.76 (2.15 - 10.55) respectively, with correspondent PARs of 28.3% (2.0% - 40.5%) and 38.2% (21.8% - 45.4%). rs11200638 in HTRA1 was another susceptible locus for AMD and the risk homozygotes were significantly susceptible for exudutive AMD (OR = 3.98, 1.88 - 8.43) with PAR of 38.9% (24.3% - 45.8%). Education status and cigarette smoking were also related to exudative AMD. After controlling for environmental risk factors, CFH and HTRA1 SNPs were independently associated with exudative AMD, with OR of 3.50 (1.45 - 8.45) for CT genotype in Y402H, 3.34 (1.33 - 8.36) for GG genotype in rs1410996 and 3.85 (1.58 - 9.42) for AA genotype in rs11200638 respectively. The interaction analysis between gene and environmental factors showed that smoking synergistically increased susceptibility of AMD for heterozygotes of rs1410996, with OR(interaction) of 7.33 (P(interaction) = 0.029).

CONCLUSIONSIn a Han Chinese population, CFH and HTRA1 polymorphisms appear to be independently and possibly additively hereditary contributors to exudative AMD. Y402H polymorphism conferred a significant but relatively lower contribution in Chinese than in Caucasians with a low frequency of risk allele. The gene-environment interaction may be a best way to encourage those with a high genetic risk to prevent AMD by avoiding modifiable factors until there is effective treatment for AMD.

Aged ; Asian Continental Ancestry Group ; Complement Factor B ; genetics ; Complement Factor H ; genetics ; Female ; Gene Frequency ; genetics ; Genetic Predisposition to Disease ; genetics ; Genotype ; High-Temperature Requirement A Serine Peptidase 1 ; Humans ; Macular Degeneration ; genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; genetics ; Risk Factors ; Serine Endopeptidases ; genetics ; Smoking ; adverse effects

OBJECTIVETo study the pulmonary pathology in patients died of fatal human influenza A(H1N1) infection.

METHODSEight cases of fatal human influenza A (H1N1) infection, including 2 autopsy cases and 6 paramortem needle puncture biopsies, were enrolled into the study. Histologic examination, immunohistochemitry, flow cytometry and Western blotting were carried out.

RESULTSThe major pathologic changes included necrotizing bronchiolitis with surrounding inflammation, diffuse alveolar damage and pulmonary hemorrhage. Influenza viral antigen expression was detected in the lung tissue by Western blotting. Immunohistochemical study demonstrated the presence of nuclear protein and hemagglutinin virus antigens in parts of trachea, bronchial epithelium and glands, alveolar epithelium, macrophages and endothelium. Flow cytometry showed that the apoptotic rate of type II pneumocytes (32.15%, 78.15%) was significantly higher than that of the controls (1.93%, 3.77%).

CONCLUSIONNecrotizing bronchiolitis, diffuse alveolar damage and pulmonary hemorrhage followed by pulmonary fibrosis in late stage are the major pathologic changes in fatal human influenza A (H1N1) infection.

Adolescent ; Adult ; Aged ; Alveolar Epithelial Cells ; pathology ; Antigens, Viral ; metabolism ; Apoptosis ; Autopsy ; Biopsy, Needle ; Bronchiolitis, Viral ; pathology ; Child ; Child, Preschool ; Female ; Hemagglutinin Glycoproteins, Influenza Virus ; metabolism ; Humans ; Influenza A Virus, H1N1 Subtype ; immunology ; Influenza, Human ; metabolism ; mortality ; pathology ; virology ; Lung ; immunology ; metabolism ; pathology ; Male ; Middle Aged ; Nuclear Proteins ; metabolism ; Pulmonary Alveoli ; pathology ; Pulmonary Fibrosis ; pathology ; Young Adult

inal event.