ObjectiveTo investigate the immunological characteristics of the patients with aplastic anemia （AA） and elevated hemogram parameters treated with Yiqi Yangxue prescription combined with Western medicine and the predictive effects of immunological indexes on elevated hemogram parameters， thus providing a reference for the prediction of the treatment efficacy and the adjustment of the treatment regimen. MethodA retrospective study was conducted， involving 77 AA patients treated with Yiqi Yangxue prescription combined with Western medicine for 6 months in 19 medical institutions including Xiyuan Hospital， China Academy of Chinese Medical Sciences from September 2018 to March 2021. The patients were assigned into two groups according to the elevations in hemogram parameters ［including hemoglobin （HGB）， white blood cell count （WBC）， platelet （PLT）， and absolute neutrophil count （ANC）］ after 6 months of treatment. One group had the elevation <50%， and the other group had the elevation ≥50% compared with the baseline. The clinical and immunological characteristics were compared between the two groups. Result① Compared with the group with HGB elevation<50%， the group with HGB elevation≥50% showed elevated level of CD3⁺ human leukocyte antigen-DR （HLA-DR）⁺ and increased proportion of patients with T-helper cell type 2 （Th2）<5%， CD8⁺≥50%， and CD3⁺HLA-DR⁺≥9% before treatment （P<0.05， P<0.01）. The multivariate Logistic regression analysis showed that CD8⁺≥50% before treatment was the independent influencing factor for HGB elevation ≥50% ［odds ratio （OR）=12.000， 95% confidence interval （CI） 2.218， 64.928， P<0.01］. ② Compared with the group with WBC elevation<50%， the group with WBC elevation≥50% showed increased proportion of patients with CD3⁺HLA-DR⁺<6% and T-box transcription factor （T-bet）≥200% before treatment （P<0.05）. The multivariate Logistic regression analysis showed that CD3⁺HLA-DR⁺<6% （OR=2.998， 95%CI 1.036， 8.680， P<0.05） and T-bet≥200% （OR=3.634， 95%CI 1.076， 12.273， P<0.05） before treatment were independent influencing factors for WBC elevation≥50%. ③ Compared with the group with PLT elevation<50%， the group with PLT elevation≥50% presented lowered Th1 and CD3⁺HLA-DR⁺ levels and increased proportion of patients with Th1<12%， CD4⁺≥6%， and CD3⁺HLA-DR⁺<5% before treatment （P<0.05， P<0.01）. The multivariate Logistic regression analysis showed that CD3⁺HLA-DR⁺<5% before treatment was the independent influencing factor for PLT elevation≥50% （OR=16.190， 95%CI of 3.430 to 76.434， P<0.01）. ④ Compared with the group with ANC elevation<50%， the group with ANC elevation≥50% showed no significant changes in the hemogram parameters before treatment. ConclusionAs for the AA patients with rapid elevation in HGB， Yiqi Yangxue prescription combined with Western medicine demonstrate significant effects in the patients with Th2<5% and CD3⁺HLA-DR⁺≥9%， especially those with CD8⁺≥50%. As for the AA patients with rapid elevation in WBC， the therapy was particularly effective in the patients with CD3⁺HLA-DR⁺<6% and T-bet≥200%. As for the AA patients with rapid growth in PLT， the therapy was particularly effective in the patients with Th1<12% and CD4⁺≥6%， especially those with CD3⁺HLA-DR⁺<5%.

OBJECTIVE：To investigate the effects of rabepr azole on the pharmacokinetic characteristics of clopidogrel and its active metabolite in healthy volunteers with different CYP2C19 genotypes. METHODS ：Healthy volunteers were selected as subjects，and then randomly divided into extensive metabolizer （EM）group，intermediate metabolizer （IM）group，and poor metabolizer（PM）group with 8 subjects in each group ，according to their CYP2C19 genotypes by random number table. In single-dose，randomized，open，two-cycle-crossover design ，each group was given Clopidogrel bisulfate tablets 300 mg or Clopidogrel bisulfate tablets 300 mg+Rabeprazole sodium enteric-coated tablets 20 mg. UPLC-MS/MS method was adopted to detect the concentration of clopidogrel and its active metabolite derivative （MP-H4）. The pharmacokinetic parameters were calculated and compared by DAS 2.0 software. RESULTS ：There was no statistical significance in clinical data as age ，height， body weight ，liver enzymes and serum creatinine among 3 kinds of metabolism subjects （P＞0.05）. Compared with subjects receiving clopidogrel alone ，cmax and AUC 0－t of clopidogrel of subjects combined with rabeprazole in EM group were increased by 36％ and 27％，while those of MP-H 4 were decreased by 34％ and 28％（P＜0.01）；cmax and AUC 0－t of clopidogrel of subjects combined with rabeprazole in IM group were increased by 19％ and 18％，while those of MP-H 4 were decreased by 19％ and 16％ （P＜0.05 or P＜0.01）；there was no statistical significance in cmax and AUC 0－t of clopidogrel and MP-H 4 in PM group after receiving rabeprazole additionally as well as tmax of clopidogrel and MP-H 4 in all metablism subjects ，compared with clopidogrel alone（P＞0.05）. CONCLUSIONS ：Among CYP2C19 EM and IM subjects ，combined use of rabeprazole can significantly increase the exposure of clopidogrel and decrease the exposure of its active metabolite MP-H 4，but has no significant impact on clopidogrel and its active metabolite in CYP2C19 PM subjects.

Objective: To describe the distribution and drug resistance of pathogens at hematology department of Jiangsu Province from 2014 to 2015 to provide reference for empirical anti-infection treatment. Methods: Pathogens were from hematology department of 26 tertiary hospitals in Jiangsu Province from 2014 to 2015. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or agar dilution method. Collection of drug susceptibility results and corresponding patient data were analyzed. Results: The separated pathogens amounted to 4 306. Gram-negative bacteria accounted for 64.26%, while the proportions of gram-positive bacteria and funguses were 26.99% and 8.75% respectively. Common gram-negative bacteria were Escherichia coli (20.48%) , Klebsiella pneumonia (15.40%) , Pseudomonas aeruginosa (8.50%) , Acinetobacter baumannii (5.04%) and Stenotropho-monas maltophilia (3.41%) respectively. CRE amounted to 123 (6.68%) . Common gram-positive bacteria were Staphylococcus aureus (4.92%) , Staphylococcus hominis (4.88%) and Staphylococcus epidermidis (4.71%) respectively. Candida albicans were the main fungus which accounted for 5.43%. The rates of Escherichia coli and Klebsiella pneumonia resistant to carbapenems were 3.5%-6.1% and 5.0%-6.3% respectively. The rates of Pseudomonas aeruginosa resistant to tobramycin and amikacin were 3.2% and 3.3% respectively. The resistant rates of Acinetobacter baumannii towards tobramycin and cefoperazone/sulbactam were both 19.2%. The rates of Stenotrophomonas maltophilia resistant to minocycline and sulfamethoxazole were 3.5% and 9.3% respectively. The rates of Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis resistant wards vancomycin were 0, 6.4% and 1.4% respectively; also, the rates of them resistant to linezolid were 1.2%, 0 and 1.6% respectively; in addition, the rates of them resistant to teicoplanin were 2.8%, 14.3% and 8.0% respectively. Furthermore, MRSA accounted for 39.15% (83/212) . Conclusions Pathogens were mainly gram-negative bacteria. CRE accounted for 6.68%. The rates of Escherichia coli and Klebsiella pneumonia resistant to carbapenems were lower compared with other antibacterial agents. The rates of gram-positive bacteria resistant to vancomycin, linezolid and teicoplanin were still low. MRSA accounted for 39.15%.

AIM To elucidate the effect of rhynchophylline(Rhy) on carotid sinus baroreceptor activity (CBA). METHODS By recording sinus nerve afferent discharge activity with isolated carotid sinus perfusion, parameters of CBA, such as peak slope (PS), peak integral value (PIV), threshold pressure (TP) and saturation pressure (SP) were examined. ①Rhy 10, 50, and 100 μmol·L-1, dissolved in K-H solution, was perfused into isolated carotid sinus, then the effects of Rhy on parameters of CBA were observed while intrasinus pressure was altered in a stepwise manner. ②NG-nitro-L-arginine methyl ester (L-NAME) 10 mmol·L-1, tetraethylammonium (TEA) 1 mmol·L-1 and Bay K8644 500 nmol·L-1 were perfused into isolated carotid sinus, and effects of them on the response of carotid baroreceptor to Rhy were observed. RESULTS ① By perfusing the isolated carotid sinus with Rhy 10 μmol·L-1, PS decreased from (19.2±0.3)% to (18.2±0.1)%·kPa-1and the PIV decreased from (219.3±3.3)% to (199.1±3.8)%, while TP and SP increased from (8.2±0.3) to (9.1±0.1)kPa and (21.5±0.1) to (22.1±0.1)kPa, respectively. By perfusing with Rhy 50 and 100 μmol·L-1, the changes in PS, TP and SP were in concentration-dependent manner, and this indicated inhibitory effect of Rhy on CBA. ②Pretreatment with L-NAME 100 μmol·L-1 did not affect inhibitory action of Rhy 50 μmol·L-1 on CBA. ③Pretreatment with TEA 1 mmol·L-1 had no effect on inhibitory effect of Rhy 50 μmol·L-1 on CBA. ④Pretreatment with Bay K8644 500 nmol·L-1 could mostly attenuate effect of Rhy 50 μmol·L-1 on CBA. CONCLUSION Rhy inhibits CBA via blocking calcium influx in baroreceptor nerve ending.

This review systematically introduces the functional connections among cardiovascular centers from spinal cord to cortex, and the mechanisms underlying pressor or depressor response of these cardiovascular centers, including the pathways, transmitters and receptors involved. The pressor or depressor response of these cardiovascular centers is mainly mediated by RVLM-sympathetic vasoconstrictor nerve system.
Blood Pressure ; physiology ; Central Nervous System ; physiology ; Cerebral Cortex ; physiology ; Humans ; Hypothalamus ; physiology ; Medulla Oblongata ; physiology ; Spinal Cord ; physiology

Extracellular single-unit discharge recording technique was used to examine the effects of Ginkgolide B (BN52021) on the discharges of neurons in CAI area of hippocampal slices and to elucidate the mechanisms involved.The results showed that:(1) In response to the application of ginkgolide B (0.1,1,10 βμmol/L; n =43) into the perfusate for 2 rain,the spontaneous discharge rates (SDR) of 42/43 (97.67%) neurons were significantly decreased in a dose-dependent manner; (2) Pretreatment with L-glutamate (L-Glu,0.2mmol/L) led to a marked increase in the SDR of all 10 (100%) neurons in an epileptiform pattern.The increased discharges were suppressed significantly after ginkgolide B (1 μmol/L) was applied into the perfusate for 2 rain; (3) In 8 neurons,perfusion of the selective L-type calcium channel agonist,Bay K 8644 (0.1 μmol/L),induced a significant increase in the discharge rate of 8/8 (100%) neurons.Ginkgolide B (1 μmoL/L) applied into the perfusate inhibited the discharges of 7/8 (87.5%) slices; (4) In 8 neurons,the broad potassium channels blocker,tetraethylammonium (TEA,1 mmol/L) completely blocked the inhibitory effect of ginkgolide B (1 μmol/L).These results suggest that ginkgolide B can inhibit the electrical activity of CAI neurons.The inhibitory effect may be related to the blockade of L-type voltage-activated calcium channel and may be concerned with delayed rectifier potassium channel (KDR),which indicated that ginkgolide B play a protective role on the central neurons.

AIM To study the central role of genistein (GST) in regulating cardiovascular function of nervous center by examining the effects of GST on the electrical activity of rat paraventricular nucleus neurons in slice preparation and to elucidate the mechanism involved. METHODS Using extracellular single-unit discharge recording technique to examine discharges of neurons in paraventricular nucleus of hypothalamic slices at the resting potential level. RESULTS ①In response to the application of GST 10, 50 and 100 μmol·L-1, respectively, in the perfusate for 2 min, the spontaneous discharge rates (SDR) of neurons in 25/26 hypothalamic slices were significantly decreased in a concentration-dependent manner. ②Pretreatment with L-glutamate 0.2 mmol·L-1 led to a marked increase in the SDR of slices in an epileptiform pattern. GST 50 μmol·L-1 significantly attenuated the increased SDR in all 7 slices. ③In 8/8 slices, the G protein-coupled inwardly rectifying K+ channels (GIRKs) antagonist, tetraethylammonium 1 mmol·L-1 completely blocked the inhibitory effect of GST 50 μmol·L-1. ④Pretreatment with nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester 50 μmol·L-1 increased SDR in all 7 slices, but did not affect the inhibitory effect of GST 50 μmol·L-1. CONCLUSION GST can inhibit the electrical activity of paraventricular neurons, and play a protective role on the central neurons. The inhibitory effect of GST may be related to the activation of GIRKs which induce K+ outward current and then engender the cell membrane hyperpolarization, but be not due to the NO release.

Effects of urotensin II (UII) on paraventricular nucleus (PVN) neurons of hypothalamus from brain slices of rats were examined by using extracellular recording technique. The results are as follows: (1) In response to application of UII (0.3, 3.0, 30.0, 300.0 nmol/L, n=39) into the perfusate for 2 min, the spontaneous discharge rates (SDR) of 32/39 (82.05% ) neurons were significantly decreased in a dose-dependent manner; (2) Pretreatment with bicuculline (BIC, 100 μmol/L), a specific GABAA receptor antagonist, led to a marked increase in SDR of 5/7 ( 71.43% ) neurons in an epileptiform pattern. The increased discharges were not significantly changed after UII ( 30.0 nmol/L ) was applied into the perfusate for 2 min; (3) Pretreatment with picrotoxin ( PIC, 50 μmol/L ), a selective blocker of Cl- channel, led to an increase in the SDR of all 12/12 (100%) neurons. The increased discharges were not influenced by the applied UII (30.0 nmol/L) for 2 min in 11/12 (91.67%) neurons; (4) Application of nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 50 μmol/L ) into the perfusate could significantly augment the SDR of 11/12 ( 91.67% ) neurons , while UII ( 30.0 nmol/L ) applied into the perfusate for 2 min led the augmented SDR of all (12/12, 100%) neurons decrease. The results suggest that UII decreases the excitability of PVN neurons of hypothalamus by potentiating GABAA receptor-mediated Cl- current.

This study is to evaluate the effect of resveratrol on carotid baroreceptor activity (CBA). The functional curve of carotid baroreceptor (FCCB) was constructed and the functional parameters of carotid baroreceptor were measured by recording sinus nerve afferent discharge in anesthetized male rats with perfused isolated carotid sinus. Resveratrol (30, 60 and 120 μmol·L-1) inhibited CBA, which shifted FCCB to the right and downward. There was a marked decrease in peak slope (PS) and peak integral value (PIV) of carotid sinus nerve charge in a concentration-dependent manner. Pretreatment with Nω-nitro-L-arginine methyl ester (L-NAME, 100 μmol·L-1), an inhibitor of nitric oxide synthase (NOS), eliminated the inhibitory effect of resveratrol. Pretreatment with Bay K8644 (an agonist of L-type calcium channel, 500 nmol·L-1) abolished the effect of resveratrol on CBA. A potent inhibitor of tyrosine phosphatase (sodium orthovanadate, 1 mmol·L-1) did not influence the effect of resveratrol on CBA. Resveratrol inhibits carotid baroreceptor activity, which may be mediated by the locally released NO and decreased calcium influx. Several studies have showed a cardioprotective effect of resveratrol, with the penetrating study of resveratrol, it may show a potential value in the clinical treatment of cardiovascular disease as an alternative medicine.

AIM To study the relationship between cardioprotective effects of resveratrol and carotid sinus baroreflex (CSB). METHODS The functional curve of the CSB was measured by recording changes in arterial pressure in anesthetized male rats with perfused isolated carotid sinus. RESULTS Resveratrol (30, 60 and 120 μmol·L-1) inhibited the CSB, which shifted the functional curve of the baroreflex to the right and upward. There were a marked decrease in peak slope and a reflex decrease of blood pressure, and also an increase in threshold pressure. Changes of these parameters showed a concentration-dependent manner. Pretreatment with Nω-nitro-L-arginine methylester (100 μmol·L-1), an inhibitor of nitric oxide synthase, and pretreatment with Bay K8644 (500 nmol·L-1), an agonist of L-type calcium channel, could both eliminate the inhibitory effect of resveratrol on CSB. A potent inhibitor of tyrosine phosphatase sodium orthovanadate (1 mmol·L-1) did not influence the effect of resveratrol on CSB. CONCLUSION Resveratrol inhibits carotid baroreflex, which may be mediated by the locally released NO and decreased calcium influx.