Wuhu decoction combined with azithromycin for treatment of Mycoplasma pneumoniae pneumonia in Asian children: a systematic review and meta analysis of randomized controlled trials.

Objective: This study constitutes a pioneering systematic review and meta analysis delving into the clinical efficacy and safety of the combined therapy involving Wuhu Decoction and azithromycin for treating Mycoplasma pneumoniae pneumonia in pediatric patients. Methods: This study conducted a comprehensive computerized search, covering 6 Chinese databases and 6 English databases, to collect randomized controlled trials related to the combined use of Wuhu Decoction and azithromycin for treating Mycoplasma pneumoniae pneumonia in pediatric patients. The search was extended until August 2023. Two independent researchers were involved in literature screening, data extraction, and bias risk assessment. Meta-analysis was performed using Stata 14.0 and RevMan 5.4 software. Additionally, meta-regression analysis and subgroup analysis were carried out on primary outcomes to identify potential sources of heterogeneity and confounding factors. Results: A total of 22 randomized controlled trials involving 2,026 patients were included in this study. The combined therapy of Wuhu Decoction and azithromycin demonstrated superior efficacy compared to azithromycin alone (RR = 1.17, 95% CI [1.13, 1.21], p < 0.00001; low certainty of evidence). Additionally, patients receiving the combination therapy experienced significantly reduced the disappearance time of fever (MD = -1.42, 95% CI [-1.84, -1.00], p < 0.00001; very low certainty of evidence), disappearance time of cough (MD = -2.08, 95% CI [-2.44, -1.71], p < 0.00001; very low certainty of evidence), disappearance of pulmonary rales (MD = -1.97, 95% CI [-2.31, -1.63], p < 0.00001; very low certainty of evidence), and disappearance time of wheezing (MD = -1.47, 95% CI [-1.72, -1.22], p < 0.00001; very low certainty of evidence). Meta-regression analysis suggested that course of disease, sample size, and age might be sources of heterogeneity. Subgroup and sensitivity analyses reaffirmed the stability of these results. Furthermore, analyses of secondary outcomes such as T lymphocytes, serum inflammatory factors, and the incidence rate of adverse reactions consistently favored the combination therapy of WHD and azithromycin over azithromycin alone, with statistically significant differences. Conclusion: Based on our meta-analysis findings, the combined therapy of Wuhu Decoction and azithromycin for treating pediatric Mycoplasma pneumoniae pneumonia exhibited superior overall efficacy in comparison to azithromycin monotherapy. However, in the included 22 studies, the majority of evaluated factors showed unclear bias risks, and a persistent bias risk was consistently present within one category. Moreover, due to the low quality of evidence, interpreting these results should be approached with caution. Hence, we emphasize the necessity for future high-quality, multicenter, and large-sample clinical randomized controlled trials. These trials are essential to provide more robust data for evidence-based research and to establish higher-quality evidence support. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023465606.

Traditional Chinese Medicine Injections Combined With Oseltamivir for Influenza: Systematic Review and Network Meta-Analysis.

Background: As a cause of respiratory tract infections in humans, influenza remains with high morbidity and mortality, with associated significant healthcare burden and increased financial burden. Traditional Chinese medicine injections (TCMIs) combined with oseltamivir (TCMIs + oseltamivir) are the representative therapeutic strategies for influenza, which is a compliant with clinical applications in China. The aim of this study was to describe the comparative efficacy and safety of TCMIs + oseltamivir in patients with influenza, based on the current evidence. Methods: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, VIP information resource integration service platform databases, and the Chinese biomedical literature service system were searched to find randomized controlled trials where TCMIs + oseltamivir are the representative therapeutic strategies for influenza, from inception until October 2021, without language restriction. Two investigators independently screened eligibility criteria, extracted data, and appraised the risk of bias with the same criteria. We conducted a network meta-analysis using the Bayesian random method for each outcome and performed the sensitivity analysis, meta-regression, and Egger's and Begg's tests for the reliability and robustness of our results. Results: Thirty-one trials including 2,893 participants proved eligible and reported on four TCMIs + oseltamivir versus oseltamivir. Network meta-analysis showed Yanhuning (YHN) +oseltamivir (MD = -1.7, 95% CrI: -2.5 to -0.88; SUCRA = 0.89; low certainty of evidence) in fever disappearance time, Tanreqing (TRQ) +oseltamivir (MD = -1.9, 95% CrI: -2.8 to -1; SUCRA = 0.97; low certainty of evidence) in cough disappearance time, and Xiyanping (XYP) +oseltamivir (OR = 5.9, 95% CrI: 3.1 to 11; SUCRA = 0.82; very low certainty of evidence) in the response rate to be more efficacious than oseltamivir alone with the best SUCRA. Based on the combined SUCRA value for primary outcomes, TRQ + oseltamivir is probably better in cough disappearance time, and XYP + oseltamivir and YHN + oseltamivir may be better in fever disappearance time than others. No significant difference in safety between the treatments. Conclusion: In patients with influenza, TCMIs + oseltamivir only partially improve flu symptoms. Overall therapeutic efficacy and safety are inconclusive, based on low to very low certainty of evidence. However, the safety remains uncertain, and TCMI treatments for influenza should be considered with caution. More high-quality studies examining the efficacy and safety of TCMIs are needed. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021286994.

Combined therapy of Xiaoer Feire Kechuan oral liquid and azithromycin for mycoplasma Pneumoniae pneumonia in children: A systematic review & meta-analysis.

BACKGROUND: Mycoplasma pneumoniae pneumonia (MPP) has high morbidity with an increased global burden. Xiaoer Feire Kechuan (XEFRKC) oral liquid comprises multiple herbal medicines and possesses numerous broad-spectrum antibacterial activities for MPP. Therefore, treatment options with XEFRKC to provide new clinical evidence for children with MPP needs to be explored. PURPOSE: This study aimed to evaluate the clinical efficacy and safety of combined treatment of XEFRKC with azithromycin (XEFRKC + azithromycin) for treating the MPP in children. METHODS: We conducted a comprehensive search in 7 databases to find the randomized controlled trials (RCTs) of XEFRKC + azithromycin treatment. Two researchers independently review the retrieval, extraction, and quality assessment of the dataset. In addition, we conducted the effect model to analyze the data and performed the meta-regression with sensitivity analysis to assess the heterogeneity and stability. RESULTS: A total of 30 RCTs with 2997 participants were included in this review. The results of primary outcomes showed that the XEFRKC + azithromycin therapy was significantly different with the azithromycin in response rate (RR = 1.18, 95% CI: 1.13 to 1.22), fever disappearance time (MD = -1.01, 95% CI: -1.18 to -0.84), cough disappearance time (MD = -2.18, 95% CI: -2.69 to -1.67), and pulmonary rales disappearance time (MD = -1.3, 95% CI: -1.71 to -0.88). For secondary outcomes and safety as well, XEFRKC + azithromycin had a significant difference compared with azithromycin. Meta-regression results showed that multiple covariables were not the source of heterogeneity. Moreover, sensitivity analysis showed that the stability of the meta-analysis results remained robust. CONCLUSIONS: For MPP in children, the XEFRKC + azithromycin therapy may be the better option compared with azithromycin alone. However, the accuracy of safety needs to be confirmed and verified with more high-quality RCTs.

White matter lesions are associated with obstructive sleep apnea hypopnea syndrome.

BACKGROUND: Study on the association of white matter lesions with obstructive sleep apnea hypopnea syndrome and its risk factors. METHODS: A recruited study with a sample of 172 patients from the department of neurology of the Third Affiliated Hospital of Southern Medical University between 2015 and 2019. RESULTS: According to the univariate analysis, the independent variables where P < 0.1 were included in the multivariate logistic regression model. After adjusting for confounding factors, the two-category logistic regression showed that Obstructive sleep apnea hypopnea syndrome (OSAHS) (OR = 8.347, 95%CI: 2.561 ~ 27.212, P < 0.001) were independent risk factors for WML, and that the prevalence of Cerebral white matter lesions (WML) increased with the severity of OSAHS (P = 0.002). In the non-OSAHS group, the mild OSAHS group, and the moderate-to-severe OSAHS group the apnea-hypopnea index (AHI) in the supine position was significantly higher than that in the left or right lateral position, showing a decreasing trend. The SaO2 < 90% total sleep time (TST SaO2 < 90%) showed an increasing trend, as did the body mass index. In the OSAHS severity groups, the AHI in the supine position was significantly higher than that in the left or right lateral position. Spearman correlation analysis showed that WML was positively related to AHI in the supine position (r = 0.209, P = 0.006). CONCLUSIONS: OSAHS was an independent risk factor for WML. There was a positive relationship between WML and AHI in the supine position. ABBREVIATIONS: AHI, apnea-hypopnea index; OSAHS, obstructive sleep apnea hypopnea syndrome; WML, white matter lesions; MRI, magnetic resonance imaging; BMI, body mass index; TSTSaO2 <90%, SaO2 <90% total sleep time; LSaO2, lowest oxygen saturation level; CI, confidence interval; OR, odds ratio.

Shuanghuanglian oral preparations combined with azithromycin for treatment of Mycoplasma pneumoniae pneumonia in Asian children: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Mycoplasma pneumoniae is one of the main causes of community-acquired pneumonia. Due to the imperfect immune system of children, this also causes Mycoplasma pneumoniae pneumonia (MPP) to be more common in children. Globally, the incidence of MPP in children is gradually increasing. This study was the first to systematically review the clinical efficacy and safety of Shuanghuanglian (SHL) oral preparations combined with azithromycin in the treatment of MPP in children. METHODS: This study fully retrieved 3 Chinese databases and 5 English databases to search the randomized controlled trials (RCTs) of SHL oral preparations combined with azithromycin in the treatment of children with MPP. The search time is from the inception to September 2020. Data extraction and risk bias evaluation were performed independently by two researchers. We conducted a Meta-analysis of all the outcome indicators. Besides, Meta-regression, subgroup analysis, and heterogeneity analysis were used for the primary outcomes to find the possible potential confounding factors. RESULTS: Finally, we included 27 RCTs involving 2884 patients. SHL oral preparations combined with azithromycin were better than azithromycin alone in response rate (RR = 1.14, 95% CI[1.11, 1.18]; low certainty evidence), disappearance time of fever(MD = -1.72, 95% CI[-2.47, -0.97]; low certainty evidence), disappearance time of cough (MD = -2.95, 95% CI[-3.55, -2.34]; low certainty evidence), and disappearance time of pulmonary rales (MD = -2.13, 95% CI[-2.88, -1.38]; low certainty evidence). The Meta-regression results showed that the course of disease, age, and method of administration may be the source of heterogeneity. Subgroup analysis and sensitivity analysis have found that the results were stable. For other related clinical symptoms, T lymphocytes, and Serum inflammatory factors, SHL oral preparations combined with azithromycin was better than azithromycin alone, and the difference was statistically significant. For adverse events with low certainty evidence, safety needs further verification. CONCLUSION: Based on the results of meta-analysis with low certainty evidence, we believed that SHL oral preparations combined with azithromycin likely be effectively improved clinical symptoms compared with azithromycin alone. Low certainty evidence showed that SHL may safety with no serious adverse events. Due to these limitations, the safety needs further verification. More high-quality, multicenter, and large-sample RCTs should be tested and verified in the future.

Therapeutic effect of Qinglong tail-wagging acupuncture method in knee osteoarthritis and its influence on inflammatory factors.

OBJECTIVES: This study explored and analyzed the healing effect of Qinglong tail-wagging acupuncture method in therapy of knee osteoarthritis and its influence on inflammatory factors. METHODS: 93 elderly patients with acute onset of knee osteoarthritis that hospitalized from March 2017 to June 2019 were admitted and randomly separated into observation group (n=48) and control group (n=45) in line with the method of random data form. The control group was given conventional electro-acupuncture, and the observation group was treated with the qinglong tail-waving acupuncture method. The clinical efficacy, pre- and post-VAS score, Lequesne and WOMAC indexes, and changes in serum inflammatory factor levels pre-and-post treatment were compared between the two sets of subjects. RESULTS: The overall response rate of clinical treatment in observation group was remarkably higher than that of the control group (P < 0.05). Besides, the VAS, Lequesne as well as WOMAC scores of two groups after treatment were significantly reduced than those in pre-treatment (P < 0.05), and the indexes in observation group were remarkably lower than those in control group (P < 0.05). In addition, the serum IL-6, NO and TNF-α concentration of the two sets of subjects in post-treatment reduced significantly than that in pre-treatment (P < 0.05), and the serum IL-6, NO and TNF-α concentration in observation group were remarkably decreased than those in control group (P < 0.05). CONCLUSION: The acupuncture method of Qinglong tail-wagging has good healing effect on remedy of elderly knee osteoarthritis. The curative method is able to improve the patients' function of knee joint and reduce the concentration of serum inflammatory factor in patients with knew osteoarthritis.

Proteomic and mechanistic study of Qingxuan Tongluo formula and curcumin in the treatment of Mycoplasma pneumoniae pneumonia.

OBJECTIVE: Mycoplasma pneumoniae (MP) is the only pathogen in the Mycoplasma family that can cause respiratory symptoms, including acute upper respiratory tract infection and bronchitis, which are often attributed to Mycoplasma pneumoniae pneumonia (MPP). MPP is one of the diseases that commonly affects the pediatric respiratory system, but its pathogenesis is unclear. This study investigated the therapeutic effects and mechanisms of Qingxuan Tongluo formula and its main component, curcumin, on MPP. METHODS: A mouse model of MPP was obtained by nasal drip of the MP strain. The effects of Qingxuan Tongluo formula and curcumin on the treatment of MPP were studied. The proteomic profiles of the alveolar lavage fluid of mice in the model group, Qingxuan Tongluo formula group and curcumin group were evaluated by LC-MS/MS. ELISA and immunohistochemistry were used to verify the possible presence of MP infection biomarkers and drug target proteins. RESULTS: Compared with the mice in the model group, the MPP mice in the Qingxuan Tongluo formula group had significantly reduced fever and cough and prolonged the cough incubation period. Moreover, the pulmonary pathology of the MPP mice was significantly improved, and the lung histopathological score was decreased. After treatment with Qingxuan Tongluo formula and curcumin, the functional and pathway abnormalities caused by MP were mainly inhibited. Levels of HSP90AA1, GRP94, ENO1 and PLG expression were verified by ELISA and immunohistochemistry. CONCLUSION: Qingxuan Tongluo formula significantly reduced fevers and cough and prolonged the cough incubation period of MPP mice. Qingxuan Tongluo formula and curcumin significantly improved the pathological changes in lung tissue caused by MP infection. Proteomics analyses indicated that Qingxuan Tongluo formula and curcumin may have therapeutic effects on MPP by regulating energy metabolism, relieving oxidative stress and activating the fibrinolytic system. ENO1 and PLG were found to be potential drug targets.

Plasma levels of matrix metalloproteinase-9: A possible marker for cold-induced stroke risk in hypertensive rats.

The cold weather is associated with an increased occurrence of acute stroke events. However, the underlying mechanisms have not yet been fully elucidated. In the present study, we investigated whether plasma matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels as well as the MMP-9/TIMP-1 ratio could be used as predictor for cold-induced stroke risk in hypertensive rats. A total of 50 male rats were subjected to either control group or 2-kidney, 2-clip (2K - 2C) group (N = 25, each), After blood pressure was stabilized, rats were placed in an intelligent artificial climate chamber and maintained on a 12-h light (22 °C)/dark (4 °C) cycle for 3 days. Plasma levels of MMP-9 and TIMP-1 were measured before and after cold exposure from 50 rats by ELISA. Pretreatment plasma MMP-9 levels were significantly higher in 2K-2C rats than in the controls (P < 0.05), TIMP-1 levels were significantly lower in 2K-2C rats than in the controls (P < 0.05), pretreatment plasma MMP-9 levels were significantly higher in those with cold-induced stroke compared to those without (P < 0.05). Logistic regression analysis showed that only plasma MMP-9 levels remained independently associated with cold-induced stroke after adjusting for potential confounders (OR, 1.17; 95% CI, 1.08 to 1.32; P < 0.007). In contrast, no correlation was observed between systolic blood pressure (SBP), TIMP-1 or MMP-9/TIMP-1 ratio and the cold-induced stroke. Higher plasma MMP-9 levels are significantly correlated with cold-induced stroke in hypertensive rats treated with intermittent cold stress. Plasma MMP-9 may be as a promising biomarker to predict the risk of cold-induced stroke events in hypertensive rats.

Renin-angiotensin system activation and imbalance of matrix metalloproteinase-9/tissue inhibitor of matrix metalloproteinase-1 in cold-induced stroke.

AIMS: In the present study, we investigated the roles of renin-angiotensin system (RAS) activation and imbalance of matrix metalloproteinase-9 (MMP-9)/tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in cold-induced stroke during chronic hypertension, as well as the protective effects of captopril and recombinant human TIMP-1 (rhTIMP-1). MAIN METHODS: Rats were randomly assigned to sham; 2-kidney, 2-clip (2K-2C); 2K-2C + captopril, and 2K-2C + rhTIMP-1 groups. After blood pressure values had stabilized, each group was randomly divided into an acute cold exposure (ACE) group (12-h light at 22 °C/12-h dark at 4 °C) and a non-acute cold exposure (NACE) group (12-h light/12-h dark at 22 °C), each of which underwent three cycles of exposure. Captopril treatment was administered via gavage (50 mg/kg/d), while rhTIMP-1 treatment was administered via the tail vein (60 µg/kg/36 h). KEY FINDINGS: In the 2K-2C group, angiotensin II (AngII) and MMP-9 levels increased in both the plasma and cortex, while no such changes in TIMP-1 expression were observed. Cold exposure further upregulated AngII and MMP-9 levels and increased stroke incidence. Captopril and rhTIMP-1 treatment inhibited MMP-9 expression and activation and decreased stroke incidence in response to cold exposure. SIGNIFICANCE: The present study is the first to demonstrate that cold exposure exacerbates imbalance between MMP-9 and TIMP-1 by activating the RAS, which may be critical in the initiation of stroke during chronic hypertension. In addition, our results suggest that captopril and rhTIMP-1 exert protective effects against cold-induced stroke by ameliorating MMP-9/TIMP-1 imbalance.

[Correlation of apolipoprotein AI, apolipoprotein B and their ratio with the severity of cerebral white matter lesions].

OBJECTIVE: To investigate the correlation of apolipoprotein AI (ApoAI), ApoB, ApoB/ApoAI and the severity of brain white matter lesions (WML). METHODS: A total of 648 patients with WML confirmed by brain magnetic resonance imaging (MRI) were divided into mild WML group (n=386) and moderate to severe WML group (n=262) according to evaluations with the Fazekas scale. The demographic data, blood biochemical parameters and the levels of ApoAI, ApoB and ApoB/AI ratio were compared between the two groups to identify the risk factors of moderate to severe WML. RESULTS: Univariate analysis showed that age, gender, hypertension, diabetes, coronary heart disease, previous stroke, homocysteine, HDL-C, ApoAI, and ApoB/AI ratio all differed significantly between the two groups (P < 0.05), but ApoB levels were similar between them (P > 0.05). Multivariate logistic regression analysis revealed that with ApoAI and ApoB/AI ratio as the continuous variables, after adjustment for the compounding factors, ApoB/AI ratio was an independent risk factor (OR=11.456, 95% CI: 3.622-36.229, P < 0.001) and ApoAI was an independent protective factor for moderate to severe WML (OR=0.068, 95% CI: 0.018-0.262, P < 0.001). With the upper quartiles of ApoAI level (1.38 g/L) and ApoB/AI ratio (0.58) as their respective cutoff values, patients with a high ApoAI level and a low ApoB/AI ratio were found to have the lowest incidence of moderate to severe WML (P < 0.001). CONCLUSIONS: An increased ApoB/AI ratio is an independent risk factor and an increased ApoAI level is an independent protective factor for moderate to severe WML.

Synthesis and kinetic evaluation of a trifunctional enzyme mimic with a dimanganese active centre.

Glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT) play crucial roles in the metabolism and homeostasis of reactive oxygen species (ROS) in living organisms. From examination of the steady state and pre-steady state kinetic behavior of natural GPX it was found that, in contrast to accepted theories, the affinity of the enzyme for H(2)O(2) rather than reduced glutathione (GSH) most significantly affects its kinetic behavior. Consequently, an enzyme mimic was produced with a similar affinity for the substrate H(2)O(2). A salicylaldehyde Schiff base containing a dimanganese centre was selected as a precursor, because it has high H(2)O(2)-binding affinity for such a relatively small molecule and similar catalytic activity to that of SOD and CAT. Selenium was also incorporated into the catalytic center to provide activity similar to that of GPX, and thus trifunctional enzymatic activity. The K(mH2O2) of the mimic (7.32×10(-2) mM) was found quite close to that of natural enzyme (1.0×10(-2) mM), indicating that the affinity of the mimic to H(2)O(2) was successfully increased to approach natural GPX. The steady state kinetic performance of the enzyme mimic showed that the ratio between k(cat)/K(mGSH) and k(cat)/ K(mH2O2) was quite similar to that of native GPX, indicating that the Mn(III)(2)(L-Se-SO(3)Na) had the same selectivity for both substrates GSH and H(2)O(2) as native GPX, which put it among the best existing GPX mimics. Moreover, the new mimic was confirmed to strongly inhibit lipid peroxidation and mitochondrial swelling, probably due to the synergism between the three antioxidant enzymatic activities.