Efficacy and safety of Qingda granule versus valsartan capsule in Chinese grade 1 hypertensive patients with low-moderate risk: A randomized, double-blind, double dummy, non-inferiority, multi-center trial.

BACKGROUND: The efficacy and safety of Qingda granule (QDG) in managing blood pressure (BP) among grade 1 hypertensive patients with low-moderate risk remain uncertain. METHODS: In the randomized, double-blind, double dummy, non-inferiority and multicenter trial, 552 patients with grade 1 hypertension at low-moderate risk were assigned at a ratio of 1:1 to receive either QDG or valsartan for 4 weeks, followed up by a subsequent 4 weeks. RESULTS: Post-treatment, clinic systolic/diastolic BPs (SBP/DBP) were reduced by a mean change of 9.18/4.04 mm Hg in the QDG group and 9.85/5.05 mm Hg in the valsartan group (SBP P = 0.47, DBP P = 0.16). Similarly, 24-hour, daytime and nighttime BPs were proportional in both groups (P > 0.05) after 4 weeks treatment. After discontinuing medications for 4 weeks, the mean reduction of clinic SBP/DBP were 0.29/0.57 mm Hg in the QDG group compared to -1.59/-0.48 mm Hg in the valsartan group (SBP P = 0.04, DBP P = 0.04). Simultaneously, the 24-hour SBP/DBP were reduced by 0.9/0.31 mm Hg in the QDG group and -1.66/-1.08 mm Hg in the valsartan group (SBP P = 0.006, DBP P = 0.02). And similar results were observed regarding the outcomes of daytime and nighttime BPs. There was no difference in occurrence of adverse events between two groups (P > 0.05). CONCLUSION: QDG proves to be efficacious for grade 1 hypertension at a low-to-medium risk, even after discontinuation of the medication for 4 weeks. These findings provide a promising option for managing grade 1 hypertension and suggest the potential for maintaining stable BP through intermittent administration of QDG. TRIAL REGISTRATION: ChiCTR2000033890.

Growth factor for therapeutic angiogenesis in ischemic heart disease: A meta-analysis of randomized controlled trials.

Aim: This study was designed to systematically evaluate the effects of growth factor (GF) for therapeutic angiogenesis on ischemic heart disease (IHD) by pooling the results of randomized controlled trials (RCTs). Methods and Results: PubMed, EMBASE, and CENTRAL databases were searched from inception to October 2022. RCTs, investigating the effects of GF therapy on IHD, were included. The risk bias of included study was assessed according to Cochrane tool. Weighted mean difference (WMD), calculated with fixed effect model or random effect model, was used to evaluate the effects of GF therapy on left ventricular ejection fraction (LVEF) and Canadian Cardiovascular Society (CCS) angina class. Relative risk (RR) was used to evaluate the effects of GF therapy on all-cause mortality, major adverse cardiovascular events (MACE) and revascularization. Meta-analysis, meta-regression analysis and publication bias analysis were performed by RevMan 5.3 or Stata 15.1 software. Twenty-nine studies involving 2899 IHD patients (1,577 patients in GF group and 1,322 patients in control group) were included. Compared with the control group, GF therapy did not reduce all-cause mortality (RR: 0.82; 95% CI: 0.54-1.24; p = 0.341), MACE [(RR: 0.83; 95% CI: 0.61-1.12; p = 0.227), revascularization (RR: 1.27, 95% CI: 0.82-1.96, p = 0.290) and CCS angina class (WMD: -0.08, 95% CI: -0.36 to 0.20, p = 0.560). However, GF therapy could increase LVEF during short-term follow-up (<1 year). Conclusion: GF for therapeutic angiogenesis was beneficial for increasing LVEF during short-term follow-up (<1 year), however, the therapy was not efficacious in decreasing all-cause mortality, MACE and revascularization.

Panax Notoginseng Saponins Inhibits Ventricular Remodeling after Myocardial Infarction in Rats Through Regulating ATF3/MAP2K3/p38 MAPK and NF κ B Pathway.

OBJECTIVE: To explore whether Panax notoginseng saponins (PNS) exhibits heart protective effect in myocardial infarction (MI) rats and to identify the potential signaling pathways involved. METHODS: MI rats induced by ligating the left anterior descending (LAD) coronary artery were assigned to sham coronary artery ligation or coronary artery ligation. Totally 36 Sprague-Dawley rats were randomly divided into sham group (distilled water, n=9), MI group (distilled water, n=9), PNS group (PNS, 40 mg/kg daily, n=9) and fosinopril group (FIP, 1.2 mg/kg daily, n=9) according to a random number table. The left ventricular morphology and function were conducted by echocardiography. Histological alterations were evaluated by the stainings of HE and Masson. The serum levels of C reactive protein (CRP), tumor necrosis factor α (TNF-α), growth differentiation factor-15 (GDF-15) and the ratio of metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP-9 (TIMP-1) were determined by ELISA. The levels of activating transcription factor 3 (ATF3), mitogen-activated protein kinase kinase 3 (MAP2K3), p38 mitogen-activated protein kinase (p38 MAPK), phosphorylation of p38 MAPK (p-p38 MAPK), transforming growth factor-ß (TGF-ß1), collagen I, nuclear factor kappa B p65 (NFκB p65), phosphorylation of NFκB p65 (p-NFκB p65), and phosphorylation of inhibitory kappa Bα (p-Iκ Bα) in hearts were measured by Western blot and immunohistochemical staining, respectively. RESULTS: PNS improved cardiac function and fibrosis in MI rats (P<0.05). The serum levels of CRP, TNF-α, GDF-15 and the ratio of MMP9/TIMP1 were reversed by PNS in MI rats. The expressions of TGF-ß1, collagen I, MAP2K3, p38 MAPK, p-p38 MAPK, NFκB p65, p-NFκB p65, and p-IκBα were down-regulated, while ATF3 increased with the treatment of PNS (P<0.05). CONCLUSIONS: PNS may improve cardiac function and fibrosis in MI rats via regulating ATF3/MAP2K3/p38 MAPK and NFκB signaling pathways. These results suggest the potential of PNS in preventing the development of ventricular remodeling in MI rats.

Onset of Coronary Heart Disease is Associated with HCMV Infection and Increased CD14 +CD16 + Monocytes in a Population of Weifang, China.

OBJECTIVE: To investigate the relationship between human cytomegalovirus (HCMV) infection and peripheral blood CD14 +CD16 + monocytes in the pathogenesis of coronary heart disease (CHD), and to elucidate the mechanism of pathogenesis in CHD by analyzing the correlation between infection, inflammation, and CHD, to provide a basis for the prevention, evaluation, and treatment of the disease. METHODS: In total, 192 patients with CHD were divided into three groups: latent CHD, angina pectoris, and myocardial infarction. HCMV-IgM and -IgG antibodies were assessed using ELISA; CD14 +CD16 + monocytes were counted using a five-type automated hematology analyzer; mononuclear cells were assessed using fluorescence-activated cell sorting; and an automatic biochemical analyzer was used to measure the levels of triglyceride, cholesterol, high- and low-density lipoprotein cholesterols, lipoprotein, hs-CRp and Hcy. RESULTS: The positive rates of HCMV-IgM and -IgG were significantly higher in the CHD groups than in the control group. HCMV infection affects lipid metabolism to promote immune and inflammatory responses. CONCLUSION: HCMV infection has a specific correlation with the occurrence and development of CHD. The expression of CD14 +CD16 + mononuclear cells in the CHD group was increased accordingly and correlated with acute HCMV infection. Thus, HCMV antibody as well as peripheral blood CD14 +CD16 + mononuclear cells can be used to monitor the occurrence and development of CHD.

Efficacy and safety of Kanglaite injection combined with first-line platinum-based chemotherapy in patients with advanced NSCLC: a systematic review and meta-analysis of 32 RCTs.

BACKGROUND: As a Chinese medicine injections, Kanglaite injection (KLT) is a complementary or alternative therapy for first-line platinum-based chemotherapy. However, the effect that certain factors, including the dose of KLT, chemotherapy cycles, evaluation criteria, or supportive treatment, have on the efficacy of the objective response rate (ORR), median survival time (MST), and adverse reactions is still unknown. METHODS: Eight databases were systematically searched from the inception dates to December 1, 2019, using the keywords Kanglaite, chemotherapy, and non small cell lung carcinoma to identify randomized clinical trials (RCTs). Analyses were performed using Review Manager 5.3 and Stata 15.1. RESULTS: There were 32 randomized controlled trials, involving 2,577 participants, that fulfilled the inclusion criteria. Compared with first-line platinum-based chemotherapy alone, KLT combined with chemotherapy could increase the ORR [risk ratio (RR), 1.41 (95% CI: 1.28 to 1.56); absolute risk difference (ARD), 0.13 (95% CI: 0.1 to 0.17)], decrease the risk ratio of adverse reactions [nausea and vomiting: RR, 0.58 (95% CI: 0.42 to 0.81); ARD, -0.17 (95% CI: -0.26 to -0.08); leukopenia: RR, 0.61 (95% CI: 0.44 to 0.86); ARD, -0.16 (95% CI: -0.24 to -0.08)], prolong MST, and increase disease control rate and Karnofsky performance status. According to the subgroup analyses, KLT combined with cisplatin or paraplatin plus paclitaxel (TP) failed to demonstrate a significant association with the ORR. And when lacking the use of supportive treatment, this combination would not decrease the RR of both adverse reactions compared with chemotherapy alone. CONCLUSIONS: KLT plus first-line platinum-based chemotherapy, except when chemotherapy regimens were TP, increased efficacy and quality of life in patients with advanced NSCLC. We are unsure whether this combination offers a low risk of adverse reactions. Additional high-quality RCTs are warranted to assess the effects of the combined therapy further.

[Meta-analysis of Xiaoer Xiaoji Zhike Oral Liqud combined with azithromycin in treatment of mycoplasma pneumonia in children].

Systematic evaluation of the effectiveness and safety of Xiaoer Xiaoji Zhike Oral Liqud combined with azithromycin in the treatment of mycoplasma pneumonia in children. Clinical literatures were retrieved from PubMed, Cochrane Library, EMbase, VIP, CNKI, SinoMed, WanFang from inception to September 2019. Two reviewers independently screened out the literatures, extracted data and assessed the risk of bias of the included studies. Then, Meta-analysis was performed by RevMan 5.3 software. A total of 17 RCT were included, involving 1 712 patients. In this study, there were two subgroups by the application approach of azithromycin: oral azithromycin subgroup and intravenous azithromycin subgroup. According to Meta-analysis results, in terms of the alleviation of clinical symptoms and signs, such as shortening of antifebrile time, cough disappeared time, rales disappearance time, and lung X-ray infiltrating shadow disappearance time, Xiaoer Xiaoji Zhike Oral Liquid combined with oral azithromycin or intravenous azithromycin were better than single-dose azithromycin; in the aspect of the improvement of the overall effective rate, the two combination subgroups were better than the single-use azithromycin; In terms of the decline of IgM, the combination subgroups were also more efficient than the single-use azithromycin, with statistically significant differences. In terms of the incidence of adverse reactions, there was no significant difference between the two combination subgroups and the single-use azithromycin in children, and no serious adverse reactions were found. In inclusion, Xiaoer Xiaoji Zhike Oral Liquid combined with azithromycin can improve the clinical efficacy in treating pediatric mycoplasma pneumonia, with a high safety. Due to the limited quantity and quality of the included studies, more high-quality studies are needed to verify the above conclusion.

[Theoretical discussion and clinical application of treating the same syndrome with different methods in "treatise on febrile and miscellaneous diseases"].

The theory of " treating same syndrome with different methods" has been widely used in traditional Chinese medicine( TCM). It originated from Treatise on Febrile and Miscellaneous Diseases,and had objective formation factors. The " syndrome" in TCM was a comprehensive manifestation of etiology,characteristics,disease location and trend of disease. Considering the rich connotation of " syndrome",the diverse treatment methods,and the complex ingredients in prescriptions,different specific methods or prescriptions have been often applied to treat the same syndrome. Therefore,based on the theory of " treating same syndrome with different methods",the concept of " prescriptions corresponding to syndromes" was extended,suggesting one syndrome treated with several different prescriptions. Moreover,the concept of " prescription corresponding to syndrome" doesn't refer to a random match between the " syndrome" and the " prescription". Instead,it would refine and objectify the " same syndrome" and seek subtle differences in symptoms,signs and chemical indicators of different diseases and individuals. It further embodied the new diagnosis and treatment model of " pathogenesis combined with pathology,drug properties combined with pharmacology". As a result,the nature of " treating same syndrome with different methods" lies in different microscopic pathological changes or trends,which traditionally expressed as the same syndrome with different symptoms,the same syndrome with different trends,and the same syndrome with different diseases and the same syndrome with different physiques. Therefore,by enriching the connotation of " syndrome",and further defining its objective pathology and development trend,the correspondence between " syndrome" and " prescription" became more precise. By carefully identifying the different characterizations,trends and prognosis in same syndrome,medical practitioners could give individual and dynamic prescriptions,so as to improve the clinical efficacy.

Considerations on nonclinical studies for immunotoxicity of monoclonal antibodies / 药物评价研究

Most monoclonal antibodies (mAbs) can induce immune responses.For immunomodulatory mAbs,immunotoxicity is the major toxicity.This article summarizes the characteristics of immunotoxicity,the factors associated with immunotoxicity,and the general considerations of nonclinical studies and evaluations.Before the clinical trials,comprehensive nonclinical studies on immunotoxicityshould be step by step conductedbased on mAbs' characteristics.If needed,some additional studies should be conducted.Attention should be paid to combination of in vivo and in vitro studies,combination of animal species and humanex vivo cells,and multiple approaches for studies.

Analysis of Renal Artery Stenosis in Patients with Heart Failure: A RASHEF Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Previous data are controversial about the association of renal artery stenosis (RAS) with clinical outcome in patients with heart failure. Definition of RAS in previous studies might not be appropriate. By definition of RAS with renal duplex sonography, we investigated the association of RAS with clinical outcome in patients with heart failure.</p><p><b>METHODS</b>In this retrospective study, we identified 164 patients with heart failure (New York Heart Association classification ≥II; left ventricular ejection fraction <50%) who had received renal duplex sonography during hospital stay. RAS was defined as renal-aortic ratio ≥3.5 or a peak systolic velocity ≥200 cm/s (or both), or occlusion of the renal artery. Categorical data of patients were compared using the Chi-square test or Fisher's exact test. Cox proportional hazards regression modeling technique was used to investigate the prognostic significance of possible predictors.</p><p><b>RESULTS</b>Finally, 143 patients were enrolled. Median follow-up time was 32 months (1-53 months). Twenty-two patients were diagnosed as RAS by renal duplex sonography, including 13 unilateral RAS (3 left RAS, 10 right RAS) and 9 bilateral RAS. There were more all-cause mortality and cardiovascular death in patients with RAS than patients without RAS. By multivariate analysis, RAS was a significant predictor for all-cause death and cardiovascular death (hazard ratio [HR] = 4.155, 95% confidence interval [CI]: 1.546-11.164, P = 0.005; and HR = 3.483, 95% CI: 1.200-10.104, P = 0.022, respectively). As for composite endpoint events, including death, nonfatal myocardial infarction, ischemic stroke or intracranial hemorrhage, rehospitalization for cardiac failure, and renal replacement therapy, only angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker was significant predictor. RAS was not a significant predictor for composite endpoint events.</p><p><b>CONCLUSIONS</b>Our data suggested that RAS is associated with a poorer clinical outcome in patients with heart failure.</p>

A novel self-sequence reaction network involving a set of six reactions in one pot: the synthesis of substituted benzothiazoles from aromatic ketones and anilines.

Employing simple and readily available aromatic ketones and anilines as starting materials resulted in the construction of 2-acylbenzothiazoles via a novel self-sequence reaction network, which assembles six reactions in one pot. The reaction network not only supplied a novel method for constructing complex molecules but also provided a typical example for logical self-organization synthesis.

Effect of transcutaneous electrical acupoint stimulation on nausea and vomiting induced by patient controlled intravenous analgesia with tramadol / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on nausea and vomiting (N&V) induced by patient controlled intravenous analgesia (PCIA) with Tramadol.</p><p><b>METHODS</b>Sixty patients who were ready to receive scheduled operation for tumor in the head-neck region and post-operation PCIA, aged 39-65 years, with the physique grades I-II of ASA, were randomized into two groups, A and B, 30 in each group. The pre-operation medication, induction of analgesia and continuous anesthesia used in the two groups were the same. TEAS on bilateral Hegu (LI4) and Neiguan (PC6) points was intermittently applied to the patients in group A starting from 30 min before analgesia induction to 24 h after operation, and the incidence and score of nausea and vomiting, antiemetic used, visual analogue scores (VAS), and PCIA pressing times in 4 time segments (0-4, 4-8, 8-12 and 12-24 h after the operation was finished) were determined. The same management was applied to patients in Group B, with sham TEAS for control.</p><p><b>RESULTS</b>The incidence and degree of N&V, as well as the number of patients who needed remedial antiemetic in Group A were less than those in Group B. The VAS score and PCIA pressing time were lower in Group A than those in Group B in the corresponding time segments respectively.</p><p><b>CONCLUSION</b>TEAS could prevent N&V induced by PCIA with Tramadol.</p>