Efficacy and safety of modified tetracycline dosing in a quadruple therapy for Helicobacter pylori:A retrospective single center study

BACKGROUND Although highly effective as a component of Helicobacter pylori(H.pylori)treatment regimen,tetracycline is associated with a high incidence of medicationrelated adverse events.Modified dosing of tetracycline as part of quadruple therapy may improve safety while providing comparable eradication rates.AIM To evaluate the efficacy and safety of modified dosing of tetracycline in patients receiving tetracycline and furazolidone-containing quadruple therapy in patients with H.pylori infection.METHODS Consecutive patients(10/2020-12/2021)who received tetracycline and furazolidone quadruple therapy for H.pylori infection at Sir Run Run Shaw Hospital were identified.All patients received tetracycline,furazolidone,proton pump inhibitor,and bismuth for 14 d as primary or rescue therapy.Modified tetracycline dose group received tetracycline 500 mg twice daily while standard group received 750 mg twice daily or 500 mg three times daily.RESULTS Three hundred and ninety-four patients[mean age=46.3±13.9,male=137(34.8%),and 309(78.4%)primary therapy]completed tetracycline and furazolidone quadruple therapy for H.pylori infection including those who received modified tetracycline dose in 157 and standard doses in 118(750 mg twice daily)and 119(500 mg three times daily).Eradication rates in the modified tetracycline dose group were 92.40%and in the standard groups,eradication rates were 93.20%for 750 mg twice daily group and 92.43%for 500 mg three times daily group,respectively,without statistical difference(P=0.959).The incidence of adverse events was lower in the modified tetracycline dose(15.3%vs 32.3%and 29.4%;P=0.002)compared to the standard dose group.CONCLUSION In a real-world experience,modified tetracycline dosing as part of tetracycline and furazolidone quadruple therapy for 14 d demonstrated high efficacy,comparable to standard tetracycline dose regimens,with a favorable safety profile.

Efficacy of maximal androgen blockade versus castration alone in the treatment of advanced prostate cancer： a retrospective clinical experience from a Chinese medical centre

In this retrospective study, we evaluated and compared the efficacy and toxicities of maximal androgen blockade （MAB） versus castration alone in Chinese patients with advanced prostate cancer. From 1996 to 2004, 608 patients with advanced prostate cancer were included in the study. Patients were retrospectively divided into two groups according to different therapeutic regimens. Of the 608 patients, 300 patients were treated with MAB （castration plus nonsteroidal antiandrogens） and the remaining 308 were treated with castration alone. The 2- and 5-year overall survival rates of these patients were 73.7% and 56%, respectively. Multivariate analysis showed that, in patients with metastatic prostate cancer, MAB was associated with not only the improvement of progression-free survival （PFS） （increased by 10 months） but also a 20.6% reduction in mortality risk compared with castration alone. In contrast, the efficacy of MAB was not superior to castration alone for patients with nonmetastatic prostate cancer. Interestingly, among patients with MAB, those using bicalutamide had a longer PFS than those using flutamide; this was especially so in patients with metastatic prostate cancer. Almost all of the toxicities due to the hormone therapy were mild to moderate and manageable. To conclude, in China, hormone therapies, including MAB and castration alone, have been standard treatments for advanced prostate cancer. For patients with nonmetastatic prostate cancer, castration alone might be adequately practical and efficient. In patients with metastatic prostate cancer, however, MAB has superior efficacy over castration alone. It is clear that MAB should be considered the first-line standard treatment for patients with metastatic prostate cancer.

Myricetin protects against lipopolysaccharide-induced disseminated intravascular coagulation by anti-inflammatory and anticoagulation effect

Objective: To explore the therapeutic effect and mechanism of myricctin on disseminated intravascular coagulation(DIC). Methods: The DIC model was established by injection of60 mg/kg LPS in KM mice, and the treatment groups were injected myricetin with different concentrations(25 or 50 mg/kg) 30 min before the model was established. Both coagulation indicators and organ function were tested, including PT, APTT, fibrinogen. AST, ALT. BUN and tissue section. In vitro, the inflammatory model of RAW 264.7 macrophage cells were established by 10 μg/mL LPS. The treatment group was treated with 50 μmol/mL myricetin for 30 min before LPS, and the expression of TNF-a and p-NF-KB was detected, further to explore the therapeutic mechanism. Results: LPS-induced DIC led to a reduction of fibrinogen and a rise of PT, APTT,AST, ALT, BUN levels, but the treatment of myricctin significantly inhibited these abnormalities. Histopathology analysis also revealed that myricetin remarkably protected the liver and renal damage. In vitro, the expression of TNF-α and p-NF-κB induced by LPS was repressed by myricetin. Conclusions: This study provides new insights into the protective effects of myricetin in LPS-induced DIC by anticoagulant and anti-inflammatory via suppressing the activation of p-NF-κB which decreased TNF-α level.

TRPA1 channel mediates organophosphate-induced delayed neuropathy

OBJECTIVE We want to investigate the mechanism of organophosphate-induced delayed neuropathy(OPIDN) and find appropriate therapeutic medicine.OPIDN,often leads to paresthesias,ataxia and paralysis,occurs in the late-stage of acute poisoning or after repeated exposures to organophosphate(OP) insecticides or nerve agents,and may contribute to the Gulf War Syndrome.METHODS FDSS Ca2^(+)-influx assays,single-cell calcium imaging and patch-clamp electrophysiology were the major testing techniques.Transfected HEK293 cells and dorsal root ganglion(DRG) neurons were used to evaluate the effects of compounds.Wild type and trpa1 knockout mice and adult hyline brown hens were used to evaluate the neuropathological damages caused by the OPs.Transmission electron microscopy imaging was used to observe the nerve injuries ultrastructurally.High-throughput screen for TRPA1 inhibitors was accomplished by Ion Works Barracuda(IWB) automated electrophysiology assay.RESULTS TRPA1(Transient receptor potential cation channel,member A1) channel mediates OPIDN.A variety of OPs,exemplified by malathion,activates TRPA1 but not other neuronal TRP channels.Malathion increases the intracellular calcium levels and upregulates the excitability of mouse DRG neurons in vitro.Mice with repeated exposures to malathion also develop local tissue nerve injuries and pain-related behaviors,which resembles the early symptoms of OPIDN.Both the neuropathological changes and the nocifensive behaviors can be attenuated by treatment of TRPA1 antagonist HC030031 or abolished by knockout of Trpa1 gene.In the classic hens OPIDN model,malathion causes nerve injuries and ataxia to a similar level as the positive inducer tri-ortho-cresyl phosphate(TOCP),which also activates TRPA1 channel.Treatment with HC030031 reduces the damages caused by malathion or TOCP.Duloxetine and Ketotifen,two commercially available drugs exhibiting TRPA1 inhibitory activity,show neuroprotective effects against OPIDN and might be used in emergency situations.CONCLUSION TRPA1 is the major mediator of OPIDN and targeting TRPA1 is an effective way for the treatment of OPIDN.

The multikinase inhibitor sorafenib induces caspase-dependent apoptosis in PC-3 prostate cancer cells

The present study investigated the effects of the multikinase inhibitor sorafenib on androgen-independent can- cer cells viability and intracellular signaling. Human androgen-independent PC-3 prostate cancer cells were treated with sorafenib. At concentration that suppresses extracellular signal-regulated kinase phosphorylation, sorafenib treatment reduced the mitochondrial transmembrane potential. Sorafenib also down-modulated the levels of mye- loid cell leukemia 1, survivin and cellular inhibitor of apoptosis protein 2. Sorafenib induced caspase-3 cleavage and the mitochondrial release of cytochrome c. However, no nuclear translocation of apoptosis inducing factor was detected after treatment and the pan-caspase inhibitor Z-VAD-FMK had an obvious protective effect against the drug. In conclusion, sorafenib induces apoptosis through a caspase-dependent mechanism with down-regulated antiapoptotic proteins in androgen-independent prostate cancer cells in vitro.

MLKL forms cation channels

OBJECTIVE To investigate how MLKL functions on the membrane and explore its electrophysiological characters and structure.METHODS The full-length human MLKL were expressed in SF21 cells and purified using glutathione-sepharose affinity chromatography.The currents of purified MLKL proteins were recorded in avoltage-clamp mode using a Warner BC-535 bilayer clamp amplifier.The currents were digitized using p CLAMP 10.2 software.HEK293 cells were cultured and transfected with MLKL plasmid.Cell viability was examined using the Cell Titer-Glo Luminescent Cell Viability Assay kit.RESULT MLKL forms cation channels that are permeable preferentially to Mg2+rather than Ca2+in the presence of Na+and K+.Moreover,each MLKL monomer contains five transmembrane helices:H1,H2,H3,H5 and H6 of the N-terminal domain which is sufficient to form channels.Finally,MLKL-induced membrane depolarization and cell death exhibit a positive correlation to its channel activity.

Liver test abnormalities in asymptomatic and mild COVID-19 patients and their association with viral shedding time

BACKGROUND Asymptomatic infections and mild symptoms are common in patients infected with the Omicron variant,and data on liver test abnormalities are rare.AIM To evaluated the clinical characteristics of asymptomatic and mild coronavirus disease 2019(COVID-19)patients with abnormal liver test results.METHODS This retrospective study included 661 laboratory-confirmed asymptomatic and mild COVID-19 patients who were treated in two makeshift hospitals in Ningbo from April 5,2022 to April 29,2022.Clinical information and viral shedding time were collected,and univariate and multivariate logistic regression models were performed in statistical analyses.RESULTS Of the 661 patients,83(12.6%)had liver test abnormalities,and 6(0.9%)had liver injuries.Abnormal liver tests revealed a reliable correlation with a history of liver disease(P<0.001)and a potential correlation with male sex and obesity(P<0.05).Elevated alanine aminotransferase was reliably associated with obesity(P<0.05)and a history of liver disease(P<0.001).Elevated aspartate transaminase(AST)was reliably correlated with a history of liver disease(P<0.001),and potentially correlated with age over 30 years(P<0.05).There was a reliable correlation between AST≥2×the upper limit of normal and a longer viral shedding time,especially in mild cases.CONCLUSION Obesity and a history of liver disease are risk factors for liver test abnormalities.Being male and an older age are potential risk factors.Attention should be given to liver tests in asymptomatic and mild COVID-19 patients,which has crucial clinical significance for evaluating the viral shedding time.

Effects of methotrexate combined with hydroxychloroquine sulfate and prednisone acetate on inflammatory response, immune function and liver and renal function in patients with systemic lupus erythematosus

Objective: To investigate the effects of methotrexate and hydroxychloroquine sulfate and prednisone on inflammatory response, immune function, liver and renal function in patients with systemic lupus erythematosus (SLE). Methods: A total of 80 cases of SLE patients according to the random data table were divided into the control group (n=40) and observation group (n=40), the control group were treated with hydroxychloroquine sulfate and prednisone treatment, on the basis of treatment of the control group, patients in the observation group in the control group were treated with methotrexate, the levels of inflammatory factors, immune function, liver and kidney function indexes in the two groups between the before treatment and after treatment were compared. Results: Comparison of the levels before treatment, the difference of the CRP, WBC, ESR, IgA, IgG, complement C3, complement C4, ALT, AST, SCr and BUN levels were not statistically significant. After treatment, the levels of CRP, ESR, IgA, IgG, ALT, AST, SCr and BUN in the observation group were significantly lower than those in the control group, and the difference was statistically significant. The levels of WBC and complement C4 in the observation group [(5.18±1.08)×109 /L, (0.22±0.05) g/L] were significantly higher than those in the control group [(4.51±0.52)×109 /L, (0.18±0.03) g/L], and there was no significant difference in the level of complement C3 between the two groups after treatment. Conclusion: Methotrexate combined with hydroxychloroquine sulfate and prednisone for the treatment of SLE can effectively reduce inflammation, improve immune function, has little effect on kidney function, high safety, which has an important clinical value.

Predictive efficacy of the 2014 International Society of Urological Pathology Gleason grading system in initially diagnosed metastatic prostate cancer

We compared the predictive ability of the 2014 and 2005 Gleason grading systems in 568 patients initially diagnosed with metastatic prostate cancer （PCa）. Outcomes included the duration of castration-resistant prostate cancer-free survival （CFS） and overall survival （OS）. Univariate analyses and log-rank tests were used to identify prognosis indicators and assess univariable differences in CFS and OS in Gleason score （GS） groups. Cox proportional hazards and area under the curves of receiver operator characteristics methods were used to evaluate the predictive efficacy of the 2005 and 2014 ISUP grading systems. Univariate analyses showed that the 2005 and 2014 grading systems were prognosticators for CFS and OS; both systems could distinguish the clinical outcome of patients with GS 6, GS 7, and GS 8-10. Using the 2014 criteria, no statistical differences in patient survival were observed between GS 3 ＋ 4 and GS 4 ＋ 3 or GS 8 and GS 9-10. The predictive ability of the 2014 and 2005 grading systems was comparable for CFS and OS （P = 0.321）. However, the 2014 grading system did not exhibit superior predictive efficacy in patients initially diagnosed with PCa and bone metastasis; trials using larger cohorts are required to confirm its predictive value. To the best of our knowledge, ours is the first study to compare the 2005 and 2014 grading systems in initially diagnosed PCa with bone metastasis. At present, we recommend that both systems should be used to predict the prognosis of patients with metastatic PCa.