Objective To explore the effects of Shenyuan Yiqi Huoxue Capsules on cardiopulmonary exercise function and quality of life in patients with ischemic cardiomyopathy.Methods Totally 66 patients with ischemic cardiomyopathy were divided into treatment group and control group using random number table method,with 33 cases in each group.Both groups received standardized Western medicine treatment,and the treatment group was additionally given Shenyuan Yiqi Huoxue Capsules,the control group was given Shenyuan Yiqi Huoxue Capsules simulator,three capsules per time,three times a day,orally.The observation period was 30 days.To evaluate the efficacy of TCM syndrome in two groups.The observation indicators included baseline data,TCM syndrome scores,cardiopulmonary exercise test detection indicators,MLHFQ score,SF-36 score,echocardiographic indicators,N-terminal pro-B-type natriuretic peptide(NT-pro BNP)and safety indicators.Results The total effective rate of the treatment group was 93.94%(31/33),while that of the control group was 78.79%(26/33).The treatment group was significantly better than the control group(P<0.05).Compared with before treatment,the TCM syndrome scores of the two groups of patients decreased(P<0.05),and after treatment,the TCM syndrome score of the treatment group was lower than that of the control group(P<0.05).Compared with before treatment,the peak oxygen uptake(peak VO2),anaerobic threshold(AT)and peak oxygen pulse(peak O2 pulse)of both groups of patients increased,while the carbon dioxide ventilation equivalent slope(VE/VCO2 slope)decreased(P<0.05).After treatment,the treatment group had higher peak VO2,AT and peak O2 pulse than the control group,while the VE/VCO2 slope was lower than the control group(P<0.05).Compared with before treatment,both groups of patients showed a decrease in MLHFQ score and an increase in SF-36 score(P<0.05);after treatment,the MLHFQ score in the treatment group was lower than that in the control group,and the SF-36 score was higher than that in the control group(P<0.05).Compared with before treatment,both groups of patients showed a decrease in left ventricular end systolic diameter,left ventricular end diastolic diameter and NT-pro BNP levels,while myocardial motion index and left ventricular ejection fraction increased(P<0.05);after treatment,the treatment group showed a decrease in left ventricular end systolic diameter,left ventricular end diastolic diameter and NT-pro BNP levels,while myocardial motion index and left ventricular ejection fraction increased(P<0.05).During the treatment period,no adverse reactions such as dizziness,nausea,vomiting or diarrhea were found in both groups of patients.Conclusion Shenyuan Yiqi Huoxue Capsules can significantly improve the clinical efficacy of ischemic cardiomyopathy patients,alleviate TCM symptoms,improve their cardiorespiratory function and quality of life.

Objective To observe the clinical efficacy of Shenyuan Yiqi Huoxue Capsules for the treatment of stable angina pectoris combined with ventricular premature beat.Methods Totally 70 patients with stable angina pectoris combined with ventricular premature beat were selected,and were divided into control group and experimental group using random number table method,with 35 cases in each group.The control group was given metoprolol tartrate tablets,25 mg/time,twice a day,orally on the basis of conventional Western medicine treatment;the experimental group was treated with Shenyuan Yiqi Huoxue Capsules on the basis of control group treatment,400 mg each time,three times a day.The course of treatment for both groups was three months.The frequency and efficacy of 24 hour ventricular premature beats,TCM syndrome scores and efficacy,heart rate variability(HRV),Seattle Angina Questionnaire(SAQ)score were observed in the two groups before and after treatment.Adverse reactions of both group were monitored.Results The experimental group shed 2 cases,and the control group shed 1 case.The total effective rate of premature ventricular contractions in the experimental group was 96.97%(32/33),while in the control group it was 82.44%(28/34).The experimental group was higher than the control group(P<0.05);the total effective rate of TCM syndrome in the experimental group was 93.94%(31/33),while in the control group it was 73.53%(25/34).The experimental group was higher than the control group(P<0.05).Compared with before treatment,the number of 24 hour ventricular premature beats in both groups decreased significantly after treatment(P<0.01).After treatment,the experimental group had significantly lower 24 hour ventricular premature beats compared to the control group(P<0.05).Compared with before treatment,both groups showed significant increases in HRV indicators and SAQ scores after treatment(P<0.01);after treatment,the HRV indicators and SAQ scores in the experimental group were significantly higher than those in the control group(P<0.05).Compared with before treatment,the TCM syndrome scores of palpitations,chest tightness,shortness of breath,fatigue,spontaneous sweating and insomnia in both groups were significantly reduced after treatment(P<0.01).After treatment,the experimental group had significantly lower TCM symptoms scores such as palpitations,chest tightness,shortness of breath,fatigue,spontaneous sweating and insomnia(P<0.05).There were no adverse reactions in either group.Conclusion Shenyuan Yiqi Huoxue Capsules have a clear effect on the treatment of stable angina pectoris combined with ventricular premature beat,which can reduce the frequency of 24 hour ventricular premature beats,relieve TCM symptoms,improve HRV,and increase the score of SAQ without clinical adverse reactions.

Objective To observe the clinical efficacy of Shenyuan Yiqi Huoxue Capsules for the treatment of stable angina pectoris combined with ventricular premature beat.Methods Totally 70 patients with stable angina pectoris combined with ventricular premature beat were selected,and were divided into control group and experimental group using random number table method,with 35 cases in each group.The control group was given metoprolol tartrate tablets,25 mg/time,twice a day,orally on the basis of conventional Western medicine treatment;the experimental group was treated with Shenyuan Yiqi Huoxue Capsules on the basis of control group treatment,400 mg each time,three times a day.The course of treatment for both groups was three months.The frequency and efficacy of 24 hour ventricular premature beats,TCM syndrome scores and efficacy,heart rate variability(HRV),Seattle Angina Questionnaire(SAQ)score were observed in the two groups before and after treatment.Adverse reactions of both group were monitored.Results The experimental group shed 2 cases,and the control group shed 1 case.The total effective rate of premature ventricular contractions in the experimental group was 96.97%(32/33),while in the control group it was 82.44%(28/34).The experimental group was higher than the control group(P<0.05);the total effective rate of TCM syndrome in the experimental group was 93.94%(31/33),while in the control group it was 73.53%(25/34).The experimental group was higher than the control group(P<0.05).Compared with before treatment,the number of 24 hour ventricular premature beats in both groups decreased significantly after treatment(P<0.01).After treatment,the experimental group had significantly lower 24 hour ventricular premature beats compared to the control group(P<0.05).Compared with before treatment,both groups showed significant increases in HRV indicators and SAQ scores after treatment(P<0.01);after treatment,the HRV indicators and SAQ scores in the experimental group were significantly higher than those in the control group(P<0.05).Compared with before treatment,the TCM syndrome scores of palpitations,chest tightness,shortness of breath,fatigue,spontaneous sweating and insomnia in both groups were significantly reduced after treatment(P<0.01).After treatment,the experimental group had significantly lower TCM symptoms scores such as palpitations,chest tightness,shortness of breath,fatigue,spontaneous sweating and insomnia(P<0.05).There were no adverse reactions in either group.Conclusion Shenyuan Yiqi Huoxue Capsules have a clear effect on the treatment of stable angina pectoris combined with ventricular premature beat,which can reduce the frequency of 24 hour ventricular premature beats,relieve TCM symptoms,improve HRV,and increase the score of SAQ without clinical adverse reactions.

Objective To explore the effects of Shenyuan Yiqi Huoxue Capsules on cardiopulmonary exercise function and quality of life in patients with ischemic cardiomyopathy.Methods Totally 66 patients with ischemic cardiomyopathy were divided into treatment group and control group using random number table method,with 33 cases in each group.Both groups received standardized Western medicine treatment,and the treatment group was additionally given Shenyuan Yiqi Huoxue Capsules,the control group was given Shenyuan Yiqi Huoxue Capsules simulator,three capsules per time,three times a day,orally.The observation period was 30 days.To evaluate the efficacy of TCM syndrome in two groups.The observation indicators included baseline data,TCM syndrome scores,cardiopulmonary exercise test detection indicators,MLHFQ score,SF-36 score,echocardiographic indicators,N-terminal pro-B-type natriuretic peptide(NT-pro BNP)and safety indicators.Results The total effective rate of the treatment group was 93.94%(31/33),while that of the control group was 78.79%(26/33).The treatment group was significantly better than the control group(P<0.05).Compared with before treatment,the TCM syndrome scores of the two groups of patients decreased(P<0.05),and after treatment,the TCM syndrome score of the treatment group was lower than that of the control group(P<0.05).Compared with before treatment,the peak oxygen uptake(peak VO2),anaerobic threshold(AT)and peak oxygen pulse(peak O2 pulse)of both groups of patients increased,while the carbon dioxide ventilation equivalent slope(VE/VCO2 slope)decreased(P<0.05).After treatment,the treatment group had higher peak VO2,AT and peak O2 pulse than the control group,while the VE/VCO2 slope was lower than the control group(P<0.05).Compared with before treatment,both groups of patients showed a decrease in MLHFQ score and an increase in SF-36 score(P<0.05);after treatment,the MLHFQ score in the treatment group was lower than that in the control group,and the SF-36 score was higher than that in the control group(P<0.05).Compared with before treatment,both groups of patients showed a decrease in left ventricular end systolic diameter,left ventricular end diastolic diameter and NT-pro BNP levels,while myocardial motion index and left ventricular ejection fraction increased(P<0.05);after treatment,the treatment group showed a decrease in left ventricular end systolic diameter,left ventricular end diastolic diameter and NT-pro BNP levels,while myocardial motion index and left ventricular ejection fraction increased(P<0.05).During the treatment period,no adverse reactions such as dizziness,nausea,vomiting or diarrhea were found in both groups of patients.Conclusion Shenyuan Yiqi Huoxue Capsules can significantly improve the clinical efficacy of ischemic cardiomyopathy patients,alleviate TCM symptoms,improve their cardiorespiratory function and quality of life.

To meet the domestic clinical demand timely,the national health commission has released three batches of encourage generic drug catalogues,which plays a good guiding role in improving the supply level and accessibility of generic drugs.Based on literature investigation,the typical cases of novel pharmaceutical preparations were analyzed,and the pharmaceutical considerations were put forward in terms formulation,manufacturing process and quality control,aimed to provide scientific reference for research and development of such drugs.

To meet the domestic clinical demand timely,the national health commission has released three batches of encourage generic drug catalogues,which plays a good guiding role in improving the supply level and accessibility of generic drugs.Based on literature investigation,the typical cases of novel pharmaceutical preparations were analyzed,and the pharmaceutical considerations were put forward in terms formulation,manufacturing process and quality control,aimed to provide scientific reference for research and development of such drugs.

Objective To investigate the infiltration of peripheral monocyte in the hippocampal CA3 area in neuralgia mice at different time points and explore the effects of the infiltration on neuralgia and the neuralgia-induced anxiety-like behavior in mice.Methods The healthy male C57 mice were randomly divided into four groups:sham,sciatic nerve branch selective injury(SNI)model(SNI),CCR2 inhibitor RS102895(SNI+RS102895)and microglial inhibitor minocycline(MC)(SNI+MC)groups.Both the sham and SNI groups were further divided into 7 days,14 days and 18 days groups,and the SNI+RS102895 and SNI+MC groups were sampled on the 18th day.Neuralgia was induced by SNI,and mechanical hyperalgesia was assessed by paw withdrawal threshold(PWTs)at different time points.Elevated plus maze(EPM)and open field test(OFT)were performed respectively two days and one day before sacrifice.Immunofluorescence was used to observe the expressions of leukocyte differentiation antigen 45(CD45)and the co-expression with microglial markers ionized calcium binding adaptor molecule-1(IBA-1),transmembrane protein 119(TMEM119),astrocyte marker glial fibrillary acidic protein(GFAP),and neuronal marker neuronal nuclei(NeuN)in the hippocampal CA3.The percentage of monocytes in the whole brain of 14 days SNI mice was determined by flow cytometry.Minocycline at 90 mg/(kg·d),RS 102895 at 5 mg/(kg·d)and saline were administered orally on the 5th to 16th day in the corresponding 18 days groups,and the effects of blocking monocyte infiltration on neuralgia and anxiety-like behavior and the expressions of CD45 and 1BA-1 in CA3 region of hippocampus were observed.Results On the first day after SNI,the PWTs of mice in the 7 days and 14 days groups decreased and continued until before sacrifice(P＜0.01).The CD45 expression did little in the 7 days sham group.Compared with the sham group at the same time point,the CD45 expression did not increase in 7 days SNI mice((P＞0.05)and increased significantly in 14 days SNI mice(P＜0.01),only slightly co-expressed with IBA-1 and TMEM119 and no co-expression with GFAP and NeuN,the percentage of monocytes in the whole brain increased significantly in 14 days SNI mice(P＜0.01).Inhibition of microglial activation or CCR2 expression reduced the expression of CD45 in the CA3 in SNI mice(P＜0.01),increased the PWTs(P＜0.01)and alleviated anxiety-like behavior in SNI mice(P＜0.01).Conclusion There was an infiltration of peripheral monocytes in the hippocampal CA3 region after 14 days of SNI-induced neuralgia,which might be involved in the maintenance of neuralgia and the development of neuralgia-induced anxiety-like behaviors.

Purpose::Vibrio vulnificus ( V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs. Methods::An increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis. Results::In mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival ( p = 0.014), reduced the serum creatinine ( p = 0.002), urea nitrogen ( p = 0.030), aspartate aminotransferase ( p = 0.029), and alanine aminotransferase ( p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1β: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1β, IL-6, TNF-α in liver (IL-1β: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1β: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid ( p = 0.225), liver ( p = 0.186), or kidney ( p = 0.637). Conclusion::Bergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus.

Objective To understand the molecular genetic background of the reported case of reemerging visceral leishmaniasis in Beijing.Methods The PCR was used to amplify the hydrophilic acylated surface protein B(K26)gene and internal transcribed spacer 1(ITS-1)sequence of ribosomal DNA.The amplified fragments were cloned and sequenced to analyze their genetic polymorphisms and to construct phylogenetic trees to determine the causative parasitic species in the infected patient and its genetic relationships.Results The K26 gene yielded a 626 bp amplicon,which exhibited significant differences in length compared to domestic epidemic strains.The amino acid sequence of this amplicon consisted of a repetitive arrangement of a 14-amino-acid motif,but amino acid substitutions were observed at certain positions.Phylogenetic analysis of the K26 sequence revealed that the Beijing strain was closely related to Leishmania infantum strains from France and Spain but distant from those in other regions of China,such as Xinjiang,Sichuan,and Hebei.Moreover,phylogenetic analysis of a 314 bp fragment amplified from the ITS-1 sequence also showed that the Beijing strain belonged to the same branch as L.infantum strains.Conclusion These results indicate that the infection in this patient was caused by L.infantum,with the strain having some differences from those in other endemic areas in China.

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.