Helicobacter pylori(Hp)is the causative agent of gastritis and peptic ulcers,and its infection is worldwide,with a high rate of infection.Antimicrobials are ineffective in the acidic environment of the stomach,thus requiring treatments that target both bacteria and stomach acid.Omeprazole and amoxicillin were the classic bactericidal and antacid combination therapy,and then developed into triple therapy,i.e.,bismuth or proton pump inhibitor+2 antimicrobials.With the increase of antimicrobial drug resistance,the triple therapy replaced by the new potassium-competitive acid-blocking agent started to be used,and bismuth quadruple therapy was adopted in areas with high rate of clarithromycin resistance,but it was still difficult to stop the declining trend of the eradication rate.Scientists are searching for strategies with non-antimicrobial drugs while continuing to delve into the mechanisms of resistance.Probiotic-assisted therapies and Hp vaccines are expected to improve eradication rates,and stimuli-responsive materials also show potential for eradicating Hp,especially the idea of altering the oxygen environment in the gastric juice so that Hp cannot survive offers a new strategy for eradication.

【Objective】 To investigate the effects of neuropathic pain induced by selective nerve injury (SNI) on intestinal microflora diversity in C57 mice. 【Methods】 36 C57 mice were randomly divided into SNI model group (n=18), sham-operation group (n=8), and control group (n=10). At day 0,1, 3, 7, and 14 after modeling, mechanical pain threshold and thermal pain sensitivity tests were carried out. At day 14 after modeling, colon content (fresh feces) from all the mice were collected for intestinal microflora diversity analysis. 【Results】 One day after modeling, the mechanical pain threshold in SNI group decreased significantly (more than 70%) due to nerve injury, and the thermal pain threshold decreased by 40%, while sham group and control group had no significant decrease. SNI group showed foot hyperalgesia, and the difference was statistically significant compared with sham group and control group (P<0.001). Compared with control group, sham-operation group had a transient decrease in thermal pain threshold on the first day after modeling (P=0.006), but there was no difference in pain threshold between the two groups on the third day after modeling. The α-diversity analysis showed that the abundance of Observed, Chao1, ACE and Simpson in SNI group was significantly lower than that in control group (P<0.05). That is, SNI group had flora disorder due to pain stimulation. Observed, Chao1, ACE, and Simpson were less abundant in sham group than in control group (P<0.05) and the change was between SNI group and control group. 【Conclusion】 Neuropathic pain induced by SNI model resulted in the decrease of mechanical pain threshold and thermal pain threshold, which leads to the reduction of intestinal flora diversity in C57 mice.

【Objective】 To analyze the cure time from diagnosis to cure of coronavirus disease 2019(COVID-19). 【Methods】 Based on the time of admission, diagnosis, and discharge of cured cases announced by the provincial and municipal health committees, the average period from diagnosis to discharge was calculated. And based on the aggregate data including the cumulative number of diagnoses, the number of curedcases and the number of deaths and their proportional relationship, we calculated the cure time. 【Results】 The cure time curve of 580 COVID-19 patients had skewed distribution, with a skewness of 1.09, a mean cure time of (14.6±6.7) days, a median of 13 days, and a 95% confidence interval (6.9, 21.0). The average cure time calculated based on the relationship between the cumulative number of diagnoses, the number of cured cases and the number of deaths was (13.3±3.5)d, with a median of 13.5 d. The average value of the cure time calculated based on the proportion of cured cases to the number of endpoints was (14.2±4.2)d, with the median number of 14.5 d. Based on the calculation of the relationship between the cumulative number of diagnosed cases, the number of cured cases and the number of deaths, the median cure time of cases with COVID-19 in Wuhan, Hubei Province, and the whole country was 15 days, 15.5 days and 15 days, respectively. The mediancure time for COVID-19cases in Wuhan, Hubei, and the whole country was 14 days. 【Conclusion】 The median cure time of COVID-19 is 13-15.5 days. There is some variation at different time of the outbreak, but there is not much difference between different regions.

【Objective】 To investigate the death time of patients with coronavirus disease 2019 (COVID-19). 【Methods】 The death time was calculated and analyzed using individual data and aggregated data through the daily notification of the epidemic situation and the death cases published on the website of the Heath Commission of China and provinces. 【Results】 In the 153 patients who died of COVID-19, the shortest time from onset to death was 4 days and the longest time was 50 days with the mean±standard deviation of (16.7±9.2) days. The median was 14 days and the 95% confidence interval was 4.6-42.9. The shortest time from admission to death was 1 day and the longest time was 50 days with the mean ± standard deviation of (12.1±7.8) days. The median was 11 days and the 95% confidence interval was 2-32.8. The time curve from diagnosis to death was skewed. The death time from diagnosis to death was 0 to 48 days with the mean ± standard deviation of (11.1±8.9) days. The median was 9 days, the interquartile interval was 10.5 days, and the 95% confidence interval was 0-35.4. It took 3 days from onset to admission and 1 day from admission to diagnosis. Aggregated data showed that the time from diagnosis to death of COVID-19 patients in China, China (except Hubei Province), Hubei Province and Wuhan City was 8, 9, 6 and 6 days, respectively. 【Conclusion】 The time from diagnosis to death of COVID-19 patients varied significantly, with the median time of 6-9 days in different regions.

Objective:To study the hemostasis effect of the ingredients in compound hemostasis patches .Methods:The effect of the ingredients in compound hemostasis patches on the clotting time was studied by the coagulation of rabbit whole blood in vitro.The models of femoral arterial injury in rats and perforation of femoral artery in pigs were established , and the effect of the ingredients in compound hemostasis patches on the bleeding time and the bleeding loss was studied .Results:The results of the whole blood coagula-tion in vitro showed that the clotting time of the three compound hemostasis patches at different concentrations and thrombin group was significantly shorter than that of the blank control group and the saline control group (P<0.01).Compared with to the blank control group, the results of rat femoral artery trauma model test showed that the three patch groups and thrombin group could significantly re -duce the bleeding loss and bleeding time (P<0.05 or P<0.01).The results of pig femoral artery perforation hemorrhage model test showed that the compound hemostasis patches could significantly reduce the bleeding time (P<0.05).Conclusion:Compound hemo-stasis patches can significantly shorten clotting time and decrease bleeding loss .

Objective:To compare the analgesic effect between living rhino horn and rhino horn in mice and rats,and to explore the possibility of living rhino horn used as a substitute of rhino horn. Methods:The analgesic effect was compared using the body tor-sion method and the formaldehyde method in mice,and the hot plate method and the thermal sting imager method in rats. Results:Compared with the control group,the living rhino horn at the dose of 0. 35,0. 7 and 1. 4 g·kg - 1 could significantly prolong the incu-bation period of body torsion induced by acetic acid(P < 0. 05 or P < 0. 01),and significantly reduce the number of body torsion(P <0. 05 or P < 0. 01). The three dose groups(0. 35,0. 7,1. 4 g·kg - 1 )of rhino horn could significantly reduce the number of body tor-sion(P < 0. 05 or P < 0. 01). After the second dose and compared with the control group,the pain threshold of high dose group(1. 4 g·kg - 1 )of living rhino horn,high and middle dose groups(0. 7,1. 4 g·kg - 1 )of rhino horn was significantly prolonged(P < 0. 05 or P < 0. 01). Compared with the control group,three dose groups(0. 175,0. 35,0. 7 g·kg - 1 )of living rhino horn and rhino horn could significantly reduce the analgesic effect in mice induced by formaldehyde in the second phase(P < 0. 01). Compared with the control group,the changes of pain threshold before and after the administration in three dose groups(110,220,440 mg·kg - 1 )of liv-ing rhino horn and high dose group(440 mg·kg - 1 )of rhino horn was significantly increased(P < 0. 05 or P < 0. 01). Conclusion:Living rhino horn can be used as a substitute of rhino horn with promising analgesia effect.

Inverse agonist is a new type of drug acting on receptors.Its research has experienced several stages, including discovery of ethylβ-carboline 3-carboxylate,activity study,proposal of the concept,two-state model,and constitutive activity theory in succession.Most G protein-coupled receptors possess constitutive activity,i.e.a proportion of receptors are in active state and can produce effects without any agonist.Inverse agonist has an affinity to receptors,but no intrinsic activity,so it cannot activate receptors.However,it can antagonize the constitutive activity of receptors,and produce an opposite effect on the corresponding agonist.Both agonist and inverse agonist can produce their effect alone with different mechanisms.Agonist activates its receptors,but inverse agonist antagonizes them.Both inverse agonist and antagonist can antagonize receptors.However,inverse agonist and antagonist antagonize the constitutive activity of receptor and the agonist’s effects,respectively.Inverse agonists can be used to treat diseases with enhanced constitutive activity,up-regulate and sensitize receptors with constitutive activity.Moreover,endogenous inverse agonists can maintain a specific physiological function.The study on inverse agonist has a theoretical significance in perfecting receptor theory as well as a clinical value in diagnosis and treatment of diseases with enhanced constitutive activity.

Objective To explore the effects of sumatriptan on the modulation of calcitonin generelated peptide(CGRP) expression and its involving intracellular signaling transduction mechanisms in rat trigeminal ganglion(TG) after organ culture.Methods Using organ culture in vitro model,54 isolated TGs of SD rats were randomly divided into fresh group ( n =6 ),control group ( n =6 ) and experimental group (n =42,6 TGs for each subgroup).Experimental group included seven subgroups,which were respectively pretreated with four different concentrations of sumatriptan,specific inhibitors of extracellular signalregulated kinases 1/2 (ERK1/2) pathway (U0126 and PD98059 ),and the inhibitor of c-Jun N-terminal kinase (JNK) (SP600125).After co-cultured with above intervention agents for 24 h,CGRP-immunoreactivity (CGRP-ir) positive neurons and CGRP-mRNA expression levels were quantified by immunohistoehemistry stain and real-time polymerase chain reaction,respectively.Phosphorylated ERK1/2 (pERK1/2) and JNK (pJNK) proteins levels were determined by Western-blotting method.Results The CGRP-ir ( + ) neurons expression levels were significantly increased after 24 h organ culture.However,0.10 and 0.50 mg/ml concentrations of sumatriptan remarkably decreased the CGRP-ir ( + ) neurons expression levels.The positive cell percentage,positive optic area,integrated optical density,mean optical density and CGRP-mRNA expression level in TG were significantly reduced than control groups (tPCP =8.652,26.382; tarea =6.220,13.917; tIA =5.606,15.904; tM14 =2.661,21.748; tmRNA =8.032,15.675.P ＜ 0.05 ).The CGRP-mRNA expressions were significantly down-regulated after co-incubation with concentration of 0.50 mg/ml sumatriptan for 24 h in TG of SD rat ( P ＜0.05 ).The levels of pERK1/2 and pJNK protein kinase detected by Western-blotting were significantly reduced by 0.50 mg/ml concentration of sumatriptan,the degrees of which were closed to the ERK1/2 and JNK pathway specific blockers.Conclusion It suggests that the optimal concentration of sumatriptan significantly down-regulates CGRP over-expression via intracellular ERK1/2 and JNK signaling transduction pathways in TG after organ culture.

The Chinese herbal medicine Tianma (Gastrodia elata) has been used for treating and preventing primary headache over thousands of years, but the exact pharmacological mechanism of the main bioactive ingredient gastrodin remains unclear. In present study, the effects of gastrodin on calcitonin gene-related peptide (CGRP) and phosphorylated extracellular signal-regulated kinase1/2 (pERK1/2) expression were observed in rat trigeminal ganglion (TG) after in vitro organ culture to explore the underlying intracellular mechanism of gastrodin on primary vascular-associated headache. CGRP-immunoreactivity (CGRP-ir) positive neurons count, positive area, mean optical density and integrated optical density by means of immunohistochemistry stain were compared at different concentrations of gastrodin, which was separately co-incubated with DMEM in SD rat TG for 24 hours. Only at 5 or 10 mmol L(-1) concentration, gastrodin demonstrated significantly concentration-dependent reduction of CGRP-ir (+) expression and its action closed to 1.2 mmol L(-1) sumatriptan succinate. While at 2.5, 20, and 40 mmol L(-1) concentration, gastrodin did not show remarkable effects on CGRP-ir (+) expression. The optimal concentration of gastrodin (5 and 10 mmol L(-1)) similarly inhibited CGRP-mRNA expression level separately compared with 1.2 mmol L(-1) sumatriptan succinate and 10 micromol L(-1) flunarizine hydrochloride, which was quantitatively analyzed by real-time PCR (RT-PCR). pERK1/2 level was examined by Western blotting after co-cultured with optimal concentration of gastrodin and effective specific ERK1/2 pathway inhibitors PD98059, U0126. The result indicated that gastrodin significantly reduced pERK1/2 protein actions similarly to ERK1/2 pathway specific blockade. It suggests ERK1/2 signaling transduction pathway may be involved in gastrodin intracellular mechanism. This study indicates gastrodin (5 and 10 mmol L(-1)) can remarkably reduce CGRP-ir (+) neuron, CGRP-mRNA and pERK1/2 expression level in cultured rat TG, with its actions similar to the effective concentration of sumatriptan succinate, flunarizine hydrochloride and specific ERK1/2 pathway blocker. The intracellular signaling transduction ERK1/2 pathway may be involved in the gastrodin reducing CGRP up-regulation in rat TG after organ culture.

Objective To observe the hemostatic effect of emergent hemostasis patch (EHP). Methods The coagulation time was studied with tube method in vitro. Hemostasis was studied with femoral artery hemorrhage models of rats and dogs as well as rabbit hepatorrhexis model in vivo. Results The clotting time of EHP of high, medium and low concentrations was (4.9±1.3)min, (5.7±1.8)min and (5.8±1.3)min, respectively, which was significantly lower than that of control (14.4±1.6)min in vitro. In femoral hemorrhage models of rats and dogs, the duration and amount of bleeding in EHP of high, medium and low doses were significantly decreased compared with those in the PVF sponge group (P<0.01 or P<0.05). The results of rabbit hepatorrhexis experiment showed that EHP of three doses obviously decreased the hemostatic time and blood loss compared with PVF sponge group (P<0.01). Conclusion EHP can shorten coagulation time and bleeding time, and reduce bleeding amount.