The autonomic nervous system plays a crucial role in regulating bone metabolism,with sympathetic activation stimulating bone resorption and inhibiting bone formation.We found that fractures lead to increased sympathet...The autonomic nervous system plays a crucial role in regulating bone metabolism,with sympathetic activation stimulating bone resorption and inhibiting bone formation.We found that fractures lead to increased sympathetic tone,enhanced osteoclast resorption,decreased osteoblast formation,and thus hastened systemic bone loss in ovariectomized(OVX)mice.However,the combined administration of parathyroid hormone(PTH)and theβ-receptor blocker propranolol dramatically promoted systemic bone formation and osteoporotic fracture healing in OVX mice.The effect of this treatment is superior to that of treatment with PTH or propranolol alone.In vitro,the sympathetic neurotransmitter norepinephrine(NE)suppressed PTH-induced osteoblast differentiation and mineralization,which was rescued by propranolol.Moreover,NE decreased the PTH-induced expression of Runx2 but enhanced the expression of Rankl and the effect of PTH-stimulated osteoblasts on osteoclastic differentiation,whereas these effects were reversed by propranolol.Furthermore,PTH increased the expression of the circadian clock gene Bmal1,which was inhibited by NE-βAR signaling.Bmal1 knockdown blocked the rescue effect of propranolol on the NE-induced decrease in PTHstimulated osteoblast differentiation.Taken together,these results suggest that propranolol enhances the anabolic effect of PTH in preventing systemic bone loss following osteoporotic fracture by blocking the negative effects of sympathetic signaling on PTH anabolism.展开更多
BACKGROUND Helicobacter pylori(H.pylori)infects over half the global population,causing gastrointestinal diseases like dyspepsia,gastritis,duodenitis,peptic ulcers,GMALT lymphoma,and gastric adenocarcinoma.Eradicating...BACKGROUND Helicobacter pylori(H.pylori)infects over half the global population,causing gastrointestinal diseases like dyspepsia,gastritis,duodenitis,peptic ulcers,GMALT lymphoma,and gastric adenocarcinoma.Eradicating H.pylori is crucial for treating and preventing these conditions.While conventional proton pump inhibitor(PPI)-based triple therapy is effective,there’s growing interest in longer acid suppression therapies.Potassium competitive acid blocker(P-CAB)triple and dual therapy are new regimens for H.pylori eradication.Initially used in Asian populations,vonoprazan(VPZ)has been recently Food and Drug Administration-approved for H.pylori eradication.AIM To assess the efficacy of regimens containing P-CABs in eradicating H.pylori infection.METHODS This study,following PRISMA 2020 guidelines,conducted a systematic review and meta-analysis by searching MEDLINE and Scopus libraries for randomized clinical trials(RCTs)or observational studies with the following command:[("Helicobacter pylori"OR"H pylori")AND("Treatment"OR"Therapy"OR"Eradication")AND("Vonaprazan"OR"Potassium-Competitive Acid Blocker"OR"P-CAB"OR"PCAB"OR"Revaprazan"OR"Linaprazan"OR"Soraprazan"OR"Tegoprazan")].Studies comparing the efficacy of P-CABs-based treatment to classical PPIs in eradicating H.pylori were included.Exclusion criteria included case reports,case series,unpublished trials,or conference abstracts.Data variables encompassed age,diagnosis method,sample sizes,study duration,intervention and control,and H.pylori eradication method were gathered by two independent reviewers.Meta-analysis was performed in R software,and forest plots were generated.RESULTS A total of 256 references were initially retrieved through the search command.Ultimately,fifteen studies(7 RCTs,7 retrospective observational studies,and 1 comparative unique study)were included,comparing P-CAB triple therapy to PPI triple therapy.The intention-to-treat analysis involved 8049 patients,with 4471 in the P-CAB intervention group and 3578 in the PPI control group across these studies.The analysis revealed a significant difference in H.pylori eradication between VPZ triple therapy and PPI triple therapy in both RCTs and observational studies[risk ratio(RR)=1.17,95%confidence interval(CI):1.11-1.22,P<0.0001]and(RR=1.13,95%CI:1.09-1.17,P<0.0001],respectively.However,no significant difference was found between tegoprazan(TPZ)triple therapy and PPI triple therapy in both RCTs and observational studies(RR=1.04,95%CI:0.93-1.16,P=0.5)and(RR=1.03,95%CI:0.97-1.10,P=0.3),respectively.CONCLUSION VPZ-based triple therapy outperformed conventional PPI-based triple therapy in eradicating H.pylori,positioning it as a highly effective first-line regimen.Additionally,TPZ-based triple therapy was non-inferior to classical PPI triple therapy.展开更多
This paper reported beta-blocker use in 21 STEMI patients over four years. The patients were between 50 - 65 years of age presenting with anterior, lateral, and inferior STEMI (ST-Elevation Myocardial Infarction). Sev...This paper reported beta-blocker use in 21 STEMI patients over four years. The patients were between 50 - 65 years of age presenting with anterior, lateral, and inferior STEMI (ST-Elevation Myocardial Infarction). Seven of the patients were female, and 14 were male. They presented to an emergency room of a rural hospital that did not provide emergency percutaneous coronary angioplasty/stenting (PTCA/stenting). The hospital is about 70 minutes from a facility that provided PTCA/ stenting—all the patients presented with typical angina chest pain with ST elevation. They are hemodynamic stable. Most patients received Lopressor 35 mg IVP, with one receiving 115 mg in a 5 mg increment. They were chest pain-free and hemodynamically before leaving the ER for the transfer for PTCA/stent. The results demonstrated that beta-blockers are effective in relieving pain in STEMI patients. Further study is needed to determine its efficacy, safety, and how to use it.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.82330078,81874010)the National Key Research and Development Program(Grant Nos.2020YFC2009004,2021YFC2501700).
文摘The autonomic nervous system plays a crucial role in regulating bone metabolism,with sympathetic activation stimulating bone resorption and inhibiting bone formation.We found that fractures lead to increased sympathetic tone,enhanced osteoclast resorption,decreased osteoblast formation,and thus hastened systemic bone loss in ovariectomized(OVX)mice.However,the combined administration of parathyroid hormone(PTH)and theβ-receptor blocker propranolol dramatically promoted systemic bone formation and osteoporotic fracture healing in OVX mice.The effect of this treatment is superior to that of treatment with PTH or propranolol alone.In vitro,the sympathetic neurotransmitter norepinephrine(NE)suppressed PTH-induced osteoblast differentiation and mineralization,which was rescued by propranolol.Moreover,NE decreased the PTH-induced expression of Runx2 but enhanced the expression of Rankl and the effect of PTH-stimulated osteoblasts on osteoclastic differentiation,whereas these effects were reversed by propranolol.Furthermore,PTH increased the expression of the circadian clock gene Bmal1,which was inhibited by NE-βAR signaling.Bmal1 knockdown blocked the rescue effect of propranolol on the NE-induced decrease in PTHstimulated osteoblast differentiation.Taken together,these results suggest that propranolol enhances the anabolic effect of PTH in preventing systemic bone loss following osteoporotic fracture by blocking the negative effects of sympathetic signaling on PTH anabolism.
文摘BACKGROUND Helicobacter pylori(H.pylori)infects over half the global population,causing gastrointestinal diseases like dyspepsia,gastritis,duodenitis,peptic ulcers,GMALT lymphoma,and gastric adenocarcinoma.Eradicating H.pylori is crucial for treating and preventing these conditions.While conventional proton pump inhibitor(PPI)-based triple therapy is effective,there’s growing interest in longer acid suppression therapies.Potassium competitive acid blocker(P-CAB)triple and dual therapy are new regimens for H.pylori eradication.Initially used in Asian populations,vonoprazan(VPZ)has been recently Food and Drug Administration-approved for H.pylori eradication.AIM To assess the efficacy of regimens containing P-CABs in eradicating H.pylori infection.METHODS This study,following PRISMA 2020 guidelines,conducted a systematic review and meta-analysis by searching MEDLINE and Scopus libraries for randomized clinical trials(RCTs)or observational studies with the following command:[("Helicobacter pylori"OR"H pylori")AND("Treatment"OR"Therapy"OR"Eradication")AND("Vonaprazan"OR"Potassium-Competitive Acid Blocker"OR"P-CAB"OR"PCAB"OR"Revaprazan"OR"Linaprazan"OR"Soraprazan"OR"Tegoprazan")].Studies comparing the efficacy of P-CABs-based treatment to classical PPIs in eradicating H.pylori were included.Exclusion criteria included case reports,case series,unpublished trials,or conference abstracts.Data variables encompassed age,diagnosis method,sample sizes,study duration,intervention and control,and H.pylori eradication method were gathered by two independent reviewers.Meta-analysis was performed in R software,and forest plots were generated.RESULTS A total of 256 references were initially retrieved through the search command.Ultimately,fifteen studies(7 RCTs,7 retrospective observational studies,and 1 comparative unique study)were included,comparing P-CAB triple therapy to PPI triple therapy.The intention-to-treat analysis involved 8049 patients,with 4471 in the P-CAB intervention group and 3578 in the PPI control group across these studies.The analysis revealed a significant difference in H.pylori eradication between VPZ triple therapy and PPI triple therapy in both RCTs and observational studies[risk ratio(RR)=1.17,95%confidence interval(CI):1.11-1.22,P<0.0001]and(RR=1.13,95%CI:1.09-1.17,P<0.0001],respectively.However,no significant difference was found between tegoprazan(TPZ)triple therapy and PPI triple therapy in both RCTs and observational studies(RR=1.04,95%CI:0.93-1.16,P=0.5)and(RR=1.03,95%CI:0.97-1.10,P=0.3),respectively.CONCLUSION VPZ-based triple therapy outperformed conventional PPI-based triple therapy in eradicating H.pylori,positioning it as a highly effective first-line regimen.Additionally,TPZ-based triple therapy was non-inferior to classical PPI triple therapy.
文摘This paper reported beta-blocker use in 21 STEMI patients over four years. The patients were between 50 - 65 years of age presenting with anterior, lateral, and inferior STEMI (ST-Elevation Myocardial Infarction). Seven of the patients were female, and 14 were male. They presented to an emergency room of a rural hospital that did not provide emergency percutaneous coronary angioplasty/stenting (PTCA/stenting). The hospital is about 70 minutes from a facility that provided PTCA/ stenting—all the patients presented with typical angina chest pain with ST elevation. They are hemodynamic stable. Most patients received Lopressor 35 mg IVP, with one receiving 115 mg in a 5 mg increment. They were chest pain-free and hemodynamically before leaving the ER for the transfer for PTCA/stent. The results demonstrated that beta-blockers are effective in relieving pain in STEMI patients. Further study is needed to determine its efficacy, safety, and how to use it.
