Objective To investigate the therapeutic effect of gabapentin combined with hemoperfusion on skin pruritus in the patients on maintenance hemodialysis(MHD).Methods A total of 72 patients with MHD complicating moderate to severe skin itching treated in Lianyungang Municipal Oriental Hospital from January 2023 to March 2024 were selected as the study subjects and divided into the observation group and control group by the random number table method,36 cases in each group.On the basis of symptomatic treat-ment,the control group was given hemodialysis 3 times a week and hemoperfusion twice a month;on the basis of the control group,the observation group orally took 1 gabapentin capsule every night,and the patients in the two groups continued to be treated for 12 weeks.The visual analogue scale(VAS)score,Pittsburgh Sleep Quality Index(PSQI)score,molecular toxin level and calcium and phosphorus metabolism were evaluated be-fore treatment,in 4,12 weeks after treatment respectively,and the occurrence of adverse reactions during treatment in the two groups was observed.Results After 4 weeks and 12 weeks of treatment,the VAS and PSQI scores of the observation group were decreased compared with those before treatment,moreover the scores of the observation group were lower than those of the control group in the same period,and the differ-ences were statistically significant(P<0.05);the VAS and PSQI scores after 4 weeks of treatment in the control group were decreased compared with those before treatment,but the difference was not statistically significant(P>0.05);and the VAS and PSQI scores after 12 weeks of treatment in the control group were decreased compared with before treatment,and the difference was statistically significant(P<0.05).After 4 weeks of treatment,the levels of Scr,BUN and β2-MG in the two groups were decreased compared with those before treatment,but the differences were not statistically significant(P>0.05);after 12 weeks of treatment,the levels of Scr,BUN and β2-MG in the two groups were decreased compared with those before treatment and after 4 weeks of treatment,and the differences were statistically significant(P<0.05),but there was no sta-tistically significant difference between the two groups(P>0.05).After 4 weeks of treatment,there was no statistically significant difference in the levels of blood Ca,P and iPTH between the two groups compared with before treatment(P>0.05);after 12 weeks of treatment,except for blood Ca,the levels of blood P and iPTH in the two groups were decreased compared with those before treatment and in 4 weeks of treatment(P<0.05),and the differences were statistically significant(P<0.05),but there was no statistical difference be-tween the two groups(P>0.05).There were no adverse reactions in the control group,and there were 3 cases of drowsiness,1 case of fatigue and 1 case of dizziness at the beginning of treatment in the observation group.The symptoms were mild without treatment and spontaneously relieved in about 1 week.Conclusion Gabap-entin combined with hemoperfusion could quickly and effectively alleviate the itchy symptoms of skin,improve the sleep quality,reduce the uremic toxin levels,and improve the calcium and phosphorus metabolism in MHD patients,with few adverse reactions,and the patients are easy to tolerate.

Objective To analyze the efficacy of arsenic-containing TCM compounds in treating high-risk myelodysplastic syndromes(HR-MDS)with spleen-kidney deficiency and toxic stagnation and blood stasis syndrome;To provide references for the clinical treatment of HR-MDS.Methods The medical records of HR-MDS with spleen-kidney deficiency and toxic stagnation and blood stasis syndrome treated with arsenic-containing TCM compounds in Xiyuan Hospital of China Academy of Chinese Medical Sciences from January 2016 to September 2022 were retrospectively analyzed.The patients were divided into arsenic-containing TCM compounds combined with demethylation drugs(HMAs)treatment group and arsenic-containing TCM compounds combined with androgen treatment group.The clinical efficacy of both groups were evaluated,including overall response rate(ORR),median overall survival(OS),1-,2-and 3-year survial rates,median progression free survival(PFS),and 1-,2-and 3-year PFS rates.Results Among 200 cases of HR-MDS,68 cases were treated with arsenic-containing TCM compounds combined with HMAs,and 132 cases were treated with arsenic-containing TCM compounds combined with androgen.The ORR was 30%,and the OS of HR-MDS after treatment was 42 months.The 1-,2-and 3-year survival rates were 78.6%,60.4%and 50.2%respectively.The median PFS was 15 months,and the 1-year,2-year and 3-year PFS rates were 57.8%,28.8%and 18.2%respectively.The ORR of 68 cases HR-MDS treated with arsenic-containing TCM compounds combined with HMAs was 44.1%.After treatment,the median OS of HR-MDS was 42 months,and the survival rates of 1-,2-and 3-years were 84%,75.6%and 61.9%respectively,and the median PFS was 24 months,and the PFS rates of 1-,2-and 3-years were 74.3%,48.5%and 35.2%,respectively.The ORR of 132 cases of HR-MDS treatmented with arsenic-containing TCM compounds combined with androgen was 26.5%,including 33.3%in the high-risk group of HR-MDS and 13.3%in the extremely high-risk group of HR-MDS.There was statistical significance between the two groups(P=0.014).After treatment,the median OS of HR-MDS was 29 months,and the survival rates of 1-,2-and 3 years were 78.6%,54.1%and 45.1%respectively.The median PFS was 13 months,and the PFS rates of 1-,2-and 3 years were 54.1%,28.2%and 12.9%respectively.Conclusion The arsenic-containing TCM compounds combined with HMAs can significantly prolong survival and delay disease progression in HR-MDS.Although the arsenic-based TCM compounds combined with androgen therapy demonstrate inferior efficacy compared to HMAs-based regimens,it has achieved significantly higher OS and PFS than historical controls,serving as an effective alternative for patients intolerant to HMAs.

BACKGROUND:Studies at home and abroad have shown that sarcopenia is closely related to metabolites.At present,the relationship between the latest 1400 blood metabolites and sarcopenia is still unknown.OBJECTIVE:To analyze the causal relationship between 1 400 metabolites and sarcopenia and its relevance with cardiovascular disease using Mendelian randomization.METHODS:Genome-wide association study(GWAS)data of sarcopenia-related characteristics(grip strength,limb muscle lean body mass,and walking speed)were obtained from the OPEN GWAS website as outcome data.A GWAS containing 1 400 metabolites was used as an exposure factor,and single nucleotide polymorphisms significantly associated with exposure factors were selected as instrumental variables.The causal association between 1 400 metabolites and sarcopenia was analyzed by"TwoSampleMR"and"gwasglue"packages of R software(V4.3.2).The research methods included inverse variance weighting,MR-Eggeer regression intercept,weighted median method,and simple mode.Heterogeneity,pleiotropic,sensitivity and other verification analysis were performed.Finally,reverse Mendelian randomization analysis was performed.RESULTS AND CONCLUSION:(1)The causal relationship between 1 400 serum metabolites and sarcopenia was analyzed by inverse variance weighting.The results showed that 1-linoleoyl-2-linoleoyl-GPC(18:2/18:3)and glycodeoxycholate 3-sulfate were protective factors,and the risk of disease decreased with the increase of metabolites(P＜0.01).(2)Two unknown metabolites(X-12822 and X-15486)and trans-3,4-methyleneheptanoate were risk factors.With the increase of two unknown metabolites(X-12822 and X-15486),the degree of low grip strength of male hands increased.Similarly,with the increase of trans-3,4-methylene heptanoate,the risk of disease also increased(P＜0.01).(3)To conclude,1-linoleoyl-2-linoleoyl-GPC(18:2/18:3)and glycodeoxycholate 3-sulfate have inhibitory effects on sarcopenia.Two unknown metabolites(X-12822 and X-15486)and trans-3,4-methyleneheptanoate can promote sarcopenia.This may be a new idea and new basis for sarcopenia research and treatment in the future.This study will also provide a reference for the study of the role of related metabolites in the Chinese population.

OBJECTIVE To establish a risk prediction model for antibiotic-associated diarrhea(AAD)in intensive care unit(ICU)patients receiving mechanical ventilation so as to provide bases for early identification of high-risk population and formulation of corresponding individualized prevention strategies.METHODS A total of 1016 pa-tients who received mechanical ventilation and were treated with antibiotics in the ICU of The First Medical Center of Chinese PLA General Hospital from Jan.1,2020 to Jun.30,2022 were retrospectively enrolled in the study and were divided into the AAD group with 200 cases and the non-AA group according to the diagnostic criteria for AAD.Multivariate logistic regression analysis was performed for risk factors for AAD in the ICU patients receiv-ing mechanical ventilation,and the nomogram prediction model was established with R software.The performance of the model was evaluated by means of receiver operating characteristic(ROC)curves and calibration curves.RESULTS Among the 1016 patients who underwent mechanical ventilation,200 had AAD,and the incidence rate of AAD was 19.69％.Multivariate logistic regression analysis showed that hemoglobulin[OR=0.990,95％CI(0.983 to 0.997)],C-reactive protein[OR=1.046,95％CI(1.009 to 1.085)],serum phosphorus[OR=0.498,95％CI(0.328 to 0.755)],serum lipase[OR=1.001,95％CI(1.000 to 1.002)],ceftriaxo ne sodium[OR=2.331,95％CI(1.253 to 4.334)],linezolid[OR=2.387,95％CI(1.329 to 4.289)],fluconazole[OR=2.083,95％CI(1.238 to 3.505)]and sedatives[OR=0.307,95％CI(0.160 to 0.590)]were the risk factors for the AAD in the ICU patients receiving mechanical ventilation.The area under ROC curve(AUC)of the predic-tion model established based on the risk factors was 0.705 for the training set,0.751 for the validation set.Hos-mer-Lemeshow test indicated that the predicated probability of the model was consistent with the actual risk for the occurrence(x2=6.057,5.304,P=0.641,0.725).CONCLUSION The nomogram model that is established based on the above influencing factors can quantitatively predict the risk for AAD in the ICU patients undergo-ing mechanical ventilation,and it has certain clinical predictive efficiency.

BACKGROUND:Studies at home and abroad have shown that sarcopenia is closely related to metabolites.At present,the relationship between the latest 1400 blood metabolites and sarcopenia is still unknown.OBJECTIVE:To analyze the causal relationship between 1 400 metabolites and sarcopenia and its relevance with cardiovascular disease using Mendelian randomization.METHODS:Genome-wide association study(GWAS)data of sarcopenia-related characteristics(grip strength,limb muscle lean body mass,and walking speed)were obtained from the OPEN GWAS website as outcome data.A GWAS containing 1 400 metabolites was used as an exposure factor,and single nucleotide polymorphisms significantly associated with exposure factors were selected as instrumental variables.The causal association between 1 400 metabolites and sarcopenia was analyzed by"TwoSampleMR"and"gwasglue"packages of R software(V4.3.2).The research methods included inverse variance weighting,MR-Eggeer regression intercept,weighted median method,and simple mode.Heterogeneity,pleiotropic,sensitivity and other verification analysis were performed.Finally,reverse Mendelian randomization analysis was performed.RESULTS AND CONCLUSION:(1)The causal relationship between 1 400 serum metabolites and sarcopenia was analyzed by inverse variance weighting.The results showed that 1-linoleoyl-2-linoleoyl-GPC(18:2/18:3)and glycodeoxycholate 3-sulfate were protective factors,and the risk of disease decreased with the increase of metabolites(P＜0.01).(2)Two unknown metabolites(X-12822 and X-15486)and trans-3,4-methyleneheptanoate were risk factors.With the increase of two unknown metabolites(X-12822 and X-15486),the degree of low grip strength of male hands increased.Similarly,with the increase of trans-3,4-methylene heptanoate,the risk of disease also increased(P＜0.01).(3)To conclude,1-linoleoyl-2-linoleoyl-GPC(18:2/18:3)and glycodeoxycholate 3-sulfate have inhibitory effects on sarcopenia.Two unknown metabolites(X-12822 and X-15486)and trans-3,4-methyleneheptanoate can promote sarcopenia.This may be a new idea and new basis for sarcopenia research and treatment in the future.This study will also provide a reference for the study of the role of related metabolites in the Chinese population.

OBJECTIVE To establish a risk prediction model for antibiotic-associated diarrhea(AAD)in intensive care unit(ICU)patients receiving mechanical ventilation so as to provide bases for early identification of high-risk population and formulation of corresponding individualized prevention strategies.METHODS A total of 1016 pa-tients who received mechanical ventilation and were treated with antibiotics in the ICU of The First Medical Center of Chinese PLA General Hospital from Jan.1,2020 to Jun.30,2022 were retrospectively enrolled in the study and were divided into the AAD group with 200 cases and the non-AA group according to the diagnostic criteria for AAD.Multivariate logistic regression analysis was performed for risk factors for AAD in the ICU patients receiv-ing mechanical ventilation,and the nomogram prediction model was established with R software.The performance of the model was evaluated by means of receiver operating characteristic(ROC)curves and calibration curves.RESULTS Among the 1016 patients who underwent mechanical ventilation,200 had AAD,and the incidence rate of AAD was 19.69％.Multivariate logistic regression analysis showed that hemoglobulin[OR=0.990,95％CI(0.983 to 0.997)],C-reactive protein[OR=1.046,95％CI(1.009 to 1.085)],serum phosphorus[OR=0.498,95％CI(0.328 to 0.755)],serum lipase[OR=1.001,95％CI(1.000 to 1.002)],ceftriaxo ne sodium[OR=2.331,95％CI(1.253 to 4.334)],linezolid[OR=2.387,95％CI(1.329 to 4.289)],fluconazole[OR=2.083,95％CI(1.238 to 3.505)]and sedatives[OR=0.307,95％CI(0.160 to 0.590)]were the risk factors for the AAD in the ICU patients receiving mechanical ventilation.The area under ROC curve(AUC)of the predic-tion model established based on the risk factors was 0.705 for the training set,0.751 for the validation set.Hos-mer-Lemeshow test indicated that the predicated probability of the model was consistent with the actual risk for the occurrence(x2=6.057,5.304,P=0.641,0.725).CONCLUSION The nomogram model that is established based on the above influencing factors can quantitatively predict the risk for AAD in the ICU patients undergo-ing mechanical ventilation,and it has certain clinical predictive efficiency.

Objective To analyze the efficacy of arsenic-containing TCM compounds in treating high-risk myelodysplastic syndromes(HR-MDS)with spleen-kidney deficiency and toxic stagnation and blood stasis syndrome;To provide references for the clinical treatment of HR-MDS.Methods The medical records of HR-MDS with spleen-kidney deficiency and toxic stagnation and blood stasis syndrome treated with arsenic-containing TCM compounds in Xiyuan Hospital of China Academy of Chinese Medical Sciences from January 2016 to September 2022 were retrospectively analyzed.The patients were divided into arsenic-containing TCM compounds combined with demethylation drugs(HMAs)treatment group and arsenic-containing TCM compounds combined with androgen treatment group.The clinical efficacy of both groups were evaluated,including overall response rate(ORR),median overall survival(OS),1-,2-and 3-year survial rates,median progression free survival(PFS),and 1-,2-and 3-year PFS rates.Results Among 200 cases of HR-MDS,68 cases were treated with arsenic-containing TCM compounds combined with HMAs,and 132 cases were treated with arsenic-containing TCM compounds combined with androgen.The ORR was 30%,and the OS of HR-MDS after treatment was 42 months.The 1-,2-and 3-year survival rates were 78.6%,60.4%and 50.2%respectively.The median PFS was 15 months,and the 1-year,2-year and 3-year PFS rates were 57.8%,28.8%and 18.2%respectively.The ORR of 68 cases HR-MDS treated with arsenic-containing TCM compounds combined with HMAs was 44.1%.After treatment,the median OS of HR-MDS was 42 months,and the survival rates of 1-,2-and 3-years were 84%,75.6%and 61.9%respectively,and the median PFS was 24 months,and the PFS rates of 1-,2-and 3-years were 74.3%,48.5%and 35.2%,respectively.The ORR of 132 cases of HR-MDS treatmented with arsenic-containing TCM compounds combined with androgen was 26.5%,including 33.3%in the high-risk group of HR-MDS and 13.3%in the extremely high-risk group of HR-MDS.There was statistical significance between the two groups(P=0.014).After treatment,the median OS of HR-MDS was 29 months,and the survival rates of 1-,2-and 3 years were 78.6%,54.1%and 45.1%respectively.The median PFS was 13 months,and the PFS rates of 1-,2-and 3 years were 54.1%,28.2%and 12.9%respectively.Conclusion The arsenic-containing TCM compounds combined with HMAs can significantly prolong survival and delay disease progression in HR-MDS.Although the arsenic-based TCM compounds combined with androgen therapy demonstrate inferior efficacy compared to HMAs-based regimens,it has achieved significantly higher OS and PFS than historical controls,serving as an effective alternative for patients intolerant to HMAs.

Objective To investigate the clinical characteristics of survival in patients with high-risk myelodysplastic syndromes(HR-MDS)and provide a reference for the clinical prognosis of patients with HR-MDS.Methods General data,blood routine test,bone marrow smear with histopathology,cytogenetics,and other clinical data of 200 patients diagnosed with HR-MDS at Xiyuan Hospital of China Academy of Chinese Medical Sciences,during the period of January 2016-September 2022,were retrospectively analyzed.The included patients were categorized into the arsenic-containing herbal combination combined with demethylating agents(HMAs)treatment group and the arsenic-containing Chinese medicine compound combined with androgen treatment group.The influence of clinical indices on the survival characteristics of each group was analyzed.Results Comparison of the impact of clinical indicators on survival in 200 patients with HR-MDS who were treated with arsenic-containing herbal compounds in combination with HMAs or androgens showed that high-risk vs.very high-risk(P=0.018),hemoglobin(Hb)<80 g/L vs.Hb≥80 g/L(P=0.035),platelet(PLT)counts<50×109 L-1 vs.PLT counts≥50×109 L-1(P<0.001),and the difference in median progression-free survival(PFS)time between myelodysplastic syndromes converted to leukemia(MDS-AML)and non-MDS-AML(P=0.003)were statistically significant.Comparison of survival effects of clinical indicators in 68 patients with HR-MDS who were treated with arsenic-containing Chinese medicine compound combined with HMAs showed that the difference in median PFS between PLT count<50×109 L-1 and PLT count≥50×109 L-1(P<0.001)and the difference in median PFS between<5 and≥5 courses of chemotherapy(P=0.018)were statistically significant.Comparison of survival effects of clinical indicators in 132 patients with HR-MDS who were treated with arsenic-containing Chinese medicine compound combined with androgens showed that Hb<80 g/L and Hg≥80 g/L(P=0.028),PLT count<50×109 L-1 and PLT count≥50×109 L-1(P=0.002),and the mean differences in PFS between MDS-AML and non-MDS-AML(P=0.024)were statistically significant.Conclusion The clinical characteristics of long-surviving patients treated with arsenic-containing herbal combination in combination with HMAs included PLT counts≥50×109 L-1 and≥5 courses of chemotherapy.The clinical characteristics of long-surviving patients treated with arsenic-containing herbal combination in combination with androgens included Hg≥80 g/L,PLT count≥50×109 L-1,and non-MDS-AML.

OBJECTIVE To investigate the effects of Qiangxin decoction on myocardial mitochondrial and energy metabolism in rats with chronic heart failure （CHF） based on mitophagy. METHODS Male SD rats were collected to establish CHF model by ligating the left anterior descending branch of coronary artery. The successful modeling rats were divided into model group， Qiangxin decoction group [12.25 g/（kg·d）， calculated by crude drug]， captopril group [10.38 mg/（kg·d）]， and Qiangxin decoction+captopril group （the same usage and dosage as single drug group） according to a random number table method， with 8 rats in each group. Another 8 normal rats were selected and received threading in the left anterior descending branch of the coronary artery without ligation as the sham operation group. Starting from the second day after successful modeling， the rats in administration groups were given relevant drug intragastrically， twice a day， for consecutive 28 days. After the last medication， the levels of adenosine triphosphate （ATP）， adenosine monophosphate （AMP） and free fatty acid （FFA） in infarcted myocardial tissues were detected， the pathological changes and mitochondrial morphology of the infarcted myocardial tissue were observed， as well as the protein expressions of B cell lymphoma-2 （Bcl-2）， Bcl-2 related X protein （Bax）， TANK-binding kinase 1 （TBK1）， p62 were detected in each group. RESULTS Compared with the sham operation group， the infarcted myocardial tissue fibrosis was changed evidently， with a large number of mitochondrial swelling and fusion， and internal cristae rupture； the levels of AMP and FFA， the protein expressions of Bax and p62 were all increased or up-regulated significantly in infarcted myocardial tissue， while the level of ATP， and the protein expressions of Bcl-2 and TBK1 were all decreased or down-regulated significantly （P＜0.05）. Compared with the model group， the pathological changes of infarcted myocardial tissue and mitochondrial swelling had been improved； the levels of AMP and FFA， and the protein expressions of Bax and p62 in infarcted myocardial tissue were significantly decreased or down-regulated in administration groups， while the level of ATP， and the protein expressions of Bcl-2 and TBK1 were increased or up-regulated significantly （P＜0.05）. And the effect of Qiangxin decoction+captopril group was better than that of single drug group. CONCLUSIONS Qiangxin decoction can alleviate myocardial fibrosis and mitochondrial swelling in CHF rats， and improve their myocardial energy metabolism， which may be related to regulating the expression of Bcl-2， Bax， TBK1 and p62 proteins and promoting myocardial mitophagy.

This study aims to investigate the effects of Japanese encephalitis virus(JEV)on TLRs signaling pathway and its regulation of the secretion of inflammatory factors during the infection of testicular interstitial cells,In this study,the mRNA levels of TLR3,TLR7,TLR8,TRIF and MyD88 genes were detected by qPCR after 1 MOI dose of JEV was inoculated into testicular stro-mal cells at different time periods.Western blot assay was used to detect the expression levels of TLR3,TLR7,TRIF and MyD88 protein at 6 h after JEV infection,and ELISA was used to detect the expression levels of IL-1β,IL-6 and TNF-α at different time periods(6,12 and 24 h).The re-sults showed as follows:After 6 h of JEV infection,the mRNA levels of TLR3,TLR7,TRIF and MyD88 genes were significantly up-regulated(P＜0.05),and the mRNA levels of TLR8 genes were down-regulated(P＜0.05).Western blot results showed that the protein expressions of TLR3,TLR7,TRIF and MyD88 were significantly up-regulated when JEV infected testicular stromal cells for 6 h(P＜0.05),which was consistent with the corresponding mRNA transcription levels.There was no significant change in TLR8 protein expression.ELISA results showed that 6 h after JEV infection of testicular stromal cells,IL-6 was significantly increased(P＜0.01),and the expressions of IL-1β and TNF-α were not changed.TLR3,TLR7,TLR8,TRIF and MyD88 were si-lenced by siRNA,and the silenced cells were inoculated with JEV for 6 h,and IL-6 expression lev-els were detected by ELISA.The results showed that silenced TLR3,TLR7,TLR8,TRIF and MyD88 could significantly reduce the increase of IL-6 secretion induced by JEV infection(P＜0.05).These results indicated that JEV could induce the expression of inflammatory factor IL-6 by activating TLR3,TLR7 and TLR8 signaling pathway after infection of testicular stromal cells.This study provides a reference for further elucidating the mechanism of reproductive disorders caused by JEV infection.