Network Meta-analysis of Heat-clearing and Detoxifying Oral Liquid of Chinese Medicines in Treatment of Children’s Hand-foot-mouth Disease：a protocol for systematic review

Review question / Objective: The type of study was clinical randomized controlled trial (RCT). The object of study is the patients with HFMD. There is no limit to gender and race. In the case of clear diagnosis standard, curative effect judgment standard and consistent baseline treatment, the experimental group was treated with pure oral liquid of traditional Chinese medicine(A: Fuganlin oral liquid, B: huangzhihua oral liquid, C: Lanqin oral liquid, D: antiviral oral liquid, E: Huangqin oral liquid, F: Pudilan oral liquid, G: Shuanghuanglian oral liquid.)and the control group was treated with ribavirin or any oral liquid of traditional Chinese medicine. The data were extracted by two researchers independently, cross checked and reviewed according to the pre-determined tables. The data extraction content is (1) Basic information (including the first author, published journal and year, research topic). (2) Relevant information (including number of cases, total number of cases, gender, age, intervention measures, course of treatment of the experimental group and the control group in the literature). (3) Design type and quality evaluation information of the included literature. (4) Outcome measures (effective rate, healing time of oral ulcer, regression time of hand and foot rash, regression time of fever, adverse reactions.). The seven traditional Chinese medicine oral liquids are comparable in clinical practice, but their actual clinical efficacy is lack of evidence-based basis. Therefore, the purpose of this study is to use the network meta-analysis method to integrate the clinical relevant evidence of direct and indirect comparative relationship, to make quantitative comprehensive statistical analysis and sequencing of different oral liquid of traditional Chinese medicine with the same evidence body for the treatment of the disease, and then to explore the advantages and disadvantages of the efficacy and safety of different oral liquid of traditional Chinese medicine to get the best treatment plan, so as to provide reference value and evidence-based medicine evidence for clinical optimization of drug selection. Condition being studied: Hand foot mouth disease (HFMD) is a common infectious disease in pediatrics caused by a variety of enteroviruses. Its clinical manifestations are mainly characterized by persistent fever, hand foot rash, oral herpes, ulcers, etc. Because it is often found in preschool children, its immune system development is not perfect, so it is very vulnerable to infection by pathogens and epidemic diseases, resulting in rapid progress of the disease. A few patients will also have neurogenic pulmonary edema Meningitis, myocarditis and other serious complications even lead to death, so effectively improve the cure rate, shorten the course of disease, prevent the deterioration of the disease as the focus of the study. In recent years, traditional Chinese medicine has played an important role in the research of antiviral treatment. Many clinical practices have confirmed that oral liquid of traditional Chinese medicine can effectively play the role of antiviral and improve the body's immunity.

Pudilan xiaoyan oral liquid (PDL) inhibit the replication of influenza A virus through regulating TLR3/MyD88 signaling pathway

Background Pudilan Xiaoyan Oral Liquid (PDL) as a famous Chinese patent medicine has been widely used for treating upper respiratory tract infection. However, the antiviral effect of PDL remain unclear. Here, the antiviral effect of in vitro and in vivo of PDL against influenza A virus were for the first time investigated. Methods The in vitro inhibitory effect of PDL on influenza A virus was investigated using MDCK cell model. The in vivo inhibitory effect on influenza virus pneumonia was evaluated with the ICR female mice (14-16 g) model infected by influenza A virus (A/FM/1/47, H1N1, mouse-adapted). Moreover, expression levels of inflammatory cytokines including TNF-α, IP10, IL-10, IL-1β, IL-6 and IFN-γ in lung tissue were measured by qRT-PCR. The potential mechanism of PDL against acute lung injury caused by influenza A virus was investigated by RT-PCR and Western blot. Results Our results indicated that in vitro PDL has a broad-spectrum inhibitory effect on different subtypes of influenza A viruses and in vivo PDL could dose-dependently prevent weight loss of mice, increase food intake and reduce mortality caused by influenza A H1N1 virus. Furthermore, PDL could markedly improve the acute lung injury caused by influenza A virus and significantly reduce the mRNA levels of inflammatory factors such as TNF-α, IP10, IL-10, IL-1β, IL-6, and IFN-γ. Mechanistic research indicated that the protective effect of PDL on viral pneumonia might be achieved by inhibiting TLR3/MyD88/IRAK4/TRAF3 signaling pathway. Conclusion PDL not only showed a good inhibitory effect on influenza A virus in vitro, but also exhibited a significant protective effect against lethal influenza virus infection in vivo. These findings provide evidence for the clinical treatment of influenza A virus infection with PDL.

Muscle-splitting mini-incision cholecystectomy under spinal anesthesia: cost-effective equitable minimally invasive surgery in laparoscopy era

Introduction: Conventional open cholecystectomy has been increasingly replaced by laparoscopy which requires resources for expensive equipment, training, and maintenance. Muscle-splitting mini-incision cholecystectomy under spinal anesthesia has comparable outcomes to laparoscopy and requires fewer resources. This study analyzes the feasibility and outcome of muscle-splitting mini-incision cholecystectomy under spinal anesthesia. Methods: All consecutive cases of muscle-splitting mini-incision cholecystectomy (MC) performed for symptomatic cholelithiasis during three years ending in December 2019, at a periphery hospital in Janakpur, province-2, Nepal, were included. Complicated cholelithiasis (biliary pancreatitis, jaundice, cholangitis, dilated common bile duct) was excluded. Written informed consents were obtained. The need for general anesthesia, complications during and after surgery, and patient satisfaction were analyzed descriptively. Ethical approval was obtained. Results: Out of 148 MC completed under spinal anesthesia, six (4.1%) required fentanyl for shoulder discomfort. Mild post-operative pain was reported by 124 (83.8%) at six hours and 146 (98.6%) at 12 hours. The intravenous drip was stopped after surgery and oral liquid with analgesics started in two hours in 143 patients (96.6%). Post-operative antibiotic was given in nine, for 2(1.4%) cholecysto-duodenal fistulas, 4(2.7%) diabetics, and 3(2%) mucoceles. The mean hospital stay was one night. Wound complications occurred in 6(2.8%). Overall, 144 (97.3%) were satisfied and would recommend the procedure to others. Histopathology revealed adenocarcinoma in one case. There was no bile-duct injury, re-surgery, or mortality. Conclusion: Muscle-splitting mini-incision open cholecystectomy (MC) under spinal anesthesia is safe and effective with early feeding, short hospital stays, less demand for resources, and good patient satisfaction.

INFLUENCE OF THE TREATMENT AND PREVENTIVE MEASURES ON THE PHYSICAL INDICATORS OF ORAL LIQUID IN CHILDREN WITH CHRONIC CATARRHIC GINGIVITIS AND DIABETES MELLITUS

The aim of our study was to find out the effect of our proposed treatment and prevention complex, which included oral administration of «Kvertulin» complex drug, «Imupret» drops, «Pikovit» multivitamin drug and «Exodent» local irrigation of the oral cavity with a solution of tooth elixir that influence on the rate of salivation and viscosity of oral fluid in children with chronic catarrhal gingivitis and diabetes mellitus.The treatment and prophylactic measures had positive effect on the homeostasis of the oral cavity, which assisted to reduce the viscosity of the oral fluid, increase the rate of salivation, as evidenced by observation of patients for 6 months. The treatment and prevention complex are recommended to use 2 times a year, as the studied indicators deteriorate over time.

Integrated Network Pharmacology and Lipidomics to Reveal the Inhibitory Effect of Qingfei Oral Liquid on Excessive Autophagy in RSV-Induced Lung Inflammation

Background: Respiratory syncytial virus (RSV) can cause varying degrees of lung inflammation in children. Qingfei Oral Liquid (QF) is effective in treating childhood RSV-induced lung inflammation (RSV-LI) in clinics, but its pharmacological profiles and mechanisms remain unclear.Methods: This study combined network Pharmacology, lipidomics, pharmacodynamics, and pathway validation to evaluate the therapeutic mechanisms of QF. Using Cytoscape (v3.8.2) and enrichment analyses from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), a global view of the putative compound-target-pathway network was created. The corresponding lipidomic profiles were then used to detect differently activated lipids, revealing the metabolic pathway, using ultra-high-performance liquid chromatography linked to hybrid Quadrupole-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS). Meanwhile, the in vivo efficiency of QF, the enrichment pathway, and the excessive autophagy inhibition mechanisms were validated in RSV-infected mice models.Results: The network pharmacology results demonstrated 117 active compounds acted directly upon 101 core targets of QF against RSV-LI. The most significantly enriched pathway was the PI3K/Akt/mTOR signaling pathway (p < 0.05). In addition, untargeted lipidomics were performed, and it was revealed that higher lung levels of DAG 30:0, DAG 30:5, DAG 32:0, DAG 16:0_18:0, DAG 17:0_17:0, DAG 34:1, DAG 36:0, DAG 36:1 in the RSV-LI group were decreased after QF administration (FDR < 0.05, FC > 1.2). Lipin-1, a key enzyme in DAG synthesis, was increased in the RSV-LI mouse model. Animal experiments further validated that QF inhibited the PI3K/Akt/mTOR signaling pathway, with lower lung levels of phosphorylated PI3K, AKT and mTOR, as well as its related proteins of lipin-1 and VPS34 (p < 0.01). Finally, pharmacodynamic investigations indicated that QF reduced airway inflammation caused by excessive autophagy by decreasing lung levels of RSV F and G proteins, Beclin-1, Atg5, and LC3B II, IL-1 and TNF-α (p < 0.05).Conclusion: Lipidomic-based network pharmacology, along with experimental validation, may be effective approaches for illustrating the therapeutic mechanism of QF in the treatment of RSV-LI.