Early effective intervention can significantly reduce all-cause mortality in prediabetic patients: a systematic review and meta-analysis based on high-quality clinical studies.

Background: Reducing the occurrence of diabetes is considered a primary criterion for evaluating the effectiveness of interventions for prediabetes. There is existing evidence that early lifestyle-based interventions can significantly decrease the incidence of diabetes. However, whether effective interventions can reduce long-term outcomes in patients, including all-cause mortality, cardiovascular risks, and the occurrence of microvascular complications, which are the most concerning issues for both patients and clinicians, remains a subject of inconsistent research findings. And there is no direct evidence to answer whether effective intervention has long-term benefits for prediabetic patients. Therefore, we conducted a systematic review and meta-analysis to assess the relationship between early effective intervention and macrovascular and microvascular complications in prediabetic patients. Methods: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched for the randomized controlled trials of lifestyle or/and drugs intervention in prediabetes from inception to 2023.9.15. Two investigators independently reviewed the included studies and extracted relevant data. Random or fixed effects model meta-analysis to derive overall relative risk (RR) with 95% CI for all-cause mortality, cardiovascular events, and microvascular complications. Results: As of September 15, 2023, a total of 7 effective intervention studies were included, comprising 26 articles out of 25,671 articles. These studies involved 26,389 patients with a total follow-up duration of 178,038.6 person-years. The results indicate that effective intervention can significantly reduce all-cause mortality in prediabetic patients without a history of cardiovascular disease by 17% (RR 0.83, 95% CI 0.70-0.98). Additionally, effective intervention reduced the incidence of retinopathy by 38% (RR 0.62, 95% CI 0.70-0.98). Furthermore, the study results suggest that women and younger individuals have lower all-cause mortality and cardiovascular mortality. Subsequently, we conducted an in-depth analysis of patients without a history of cardiovascular disease. The results revealed that prediabetic patients with a 10-year cardiovascular risk >10% experienced more significant benefits in terms of all-cause mortality (P=0.01). When comparing the results of all-cause mortality and cardiovascular mortality from the Da Qing Diabetes Prevention Outcome Study longitudinally, it was evident that the duration of follow-up is a key factor influencing long-term benefits. In other words, the beneficial effects become more pronounced as the intervention duration reaches a certain threshold. Conclusion: Early effective intervention, which significantly reduces the incidence of diabetes, can effectively lower all-cause mortality in prediabetic patients without a history of cardiovascular disease (especially those with a 10-year cardiovascular risk >10%), with women and younger individuals benefiting more significantly. Additionally, the duration of follow-up is a key factor influencing outcomes. The conclusions of this study can provide evidence-based guidance for the clinical treatment of prediabetic patients to prevent cardiovascular and microvascular complications. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42020160985.

Parallelism and non-parallelism in diabetic nephropathy and diabetic retinopathy.

Diabetic nephropathy (DN) and diabetic retinopathy (DR), as microvascular complications of diabetes mellitus, are currently the leading causes of end-stage renal disease (ESRD) and blindness, respectively, in the adult working population, and they are major public health problems with social and economic burdens. The parallelism between the two in the process of occurrence and development manifests in the high overlap of disease-causing risk factors and pathogenesis, high rates of comorbidity, mutually predictive effects, and partial concordance in the clinical use of medications. However, since the two organs, the eye and the kidney, have their unique internal environment and physiological processes, each with specific influencing molecules, and the target organs have non-parallelism due to different pathological changes and responses to various influencing factors, this article provides an overview of the parallelism and non-parallelism between DN and DR to further recognize the commonalities and differences between the two diseases and provide references for early diagnosis, clinical guidance on the use of medication, and the development of new drugs.

The rational dose for MaXingShiGan decoction is crucial for its clinical effectiveness in treating bronchial pneumonia: three randomized, double-blind, dose-parallel controlled clinical studies.

Objective: Evaluate the impact of adjusting the overall dose, Gypsum Fibrosum [Mineral; Gypsum] (ShiGao, SG) dose, and Prunus armeniaca L. [Rosaceae; Semen Armeniacae Amarum] (KuXingRen, KXR) dose on the efficacy of MaXingShiGan Decoction (MXSG) in treating children with bronchial pneumonia (Wind-heat Blocking the Lung), in order to provide strategy supported by high-quality evidence for the selection of rational clinical doses of MXSG. Methods: Based on the basic dose of MXSG, we conducted three randomized, double-blind, dose parallel controlled, multicenter clinical trials, involving adjustments to the overall dose, SG dose, and KXR dose, and included 120 children with bronchial pneumonia (Wind-heat Blocking the Lung) respectively. And the patients were divided into low, medium, and high dose groups in a 1:1:1 ratio, with 40 cases in each group. The intervention period lasted for 10 days. The primary outcome was the clinical cured rate, while the secondary outcomes included the effectiveness in alleviating major symptoms of bronchial pneumonia (including fever, cough, dyspnea, and phlegm congestion). And the occurrence of adverse events was recorded. Results: We first recorded and analyzed the baseline characteristics of the three studies, including age, gender, height, and so on. The results indicated that there were no significant differences among the dose groups within each study. For the study adjusting the overall dose of MXSG, the results showed that both the medium-dose group and high-dose group had significantly higher clinical cured rates compared to the low-dose group (Chi-square value 9.01, p = 0.0111). However, there was no significant benefit between the high-dose group and the medium-dose group (81.58% vs. 81.08%). Regarding phlegm congestion, excluding fever, cough, and dyspnea, both the medium-dose group and high-dose group had significantly higher clinical cured rates than the low-dose group (Chi-square value 6.31, p = 0.0426), and there was no significant benefit between the high-dose group and the medium-dose group (69.23% vs. 75.00%). A total of 5 adverse events were observed, of which only 1 case in the medium-dose group was possibly related to the experimental medication. For the study adjusted the SG dose in MXSG, the results showed that the high-dose group had the highest clinical cured rate, but the inter-group difference was not statistically significant (Chi-square value 3.36, p = 0.1864). The area under the curve (AUC) for cough in the medium-dose group was significantly lower than in the low-dose group and high-dose group (F-test value 3.14, p = 0.0471). Although no significant differences were observed in fever and dyspnea among the groups, the AUC in the high-dose group was lower than in the medium-dose and low-dose groups. In comparing the complete defervescence time, both the high-dose group (p < 0.0001) and the medium-dose group (p = 0.0015) achieved faster than the low-dose group. The high-dose group slightly outperformed the medium-dose group (0.50 (0.50, 0.80) vs. 0.80 (0.40, 1.40)), although the difference was not significant. In the medium-dose group, 1 adverse event was observed, but it was not related to the experimental medication. For the study adjusted the KXR dose in MXSG, the results showed that both the medium-dose group and high-dose group had significantly higher cured rates compared to the low-dose group (Chi-square value 47.05, p < 0.0001). However, there was no significant benefit comparing the high-dose group to the medium-dose group (90.00% vs. 92.50%). Regarding clinical symptoms, the results indicated that for cough (F-test value 3.16, p = 0.0460) and phlegm congestion (F-test value 3.84, p = 0.0243), the AUC for both the medium-dose group and high-dose group were significantly lower than in the low-dose group. Although there was benefit in the high-dose group compared to the medium-dose group, it was not statistically significant. No adverse events were observed during the study period. Conclusion: The synthesis of the three conducted clinical studies collectively indicates that for children with bronchial pneumonia (Wind-heat Blocking the Lung), the basic clinical dose of MXSG may represents an optimal intervention dose based on the accumulated clinical experience of doctors. If the dose is insufficient, the clinical effects might be compromised, but using a higher dose does not significantly enhance benefits. Concerning different symptoms, increasing the overall formula's dose has a favorable impact on improving phlegm congestion, increasing the SG is effective in improving symptoms such as fever, cough, and dyspnea, while higher dose of KXR is effective in alleviating cough and phlegm congestion. These findings suggest that for MXSG, achieving the optimal intervention dose is crucial to achieve better clinical efficacy. For the SG and KXR, if certain symptoms are more severe, increasing the dose can be considered within safe limits, can lead to significant clinical benefits in symptom improvement. This also explains why the dose of MXSG might vary among clinical doctors, while maintaining a balance between safety and effectiveness. Of course, our study is still exploratory clinical trials, and further studies are needed to confirm our findings. Clinical Trial Registration: https://www.chictr.org.cn/index.html; Identifier: ChiCTR-TRC-13003093, ChiCTR-TRC-13003099.

The ideal treatment timing for diabetic retinopathy: the molecular pathological mechanisms underlying early-stage diabetic retinopathy are a matter of concern.

Diabetic retinopathy (DR) is a prevalent complication of diabetes, significantly impacting patients' quality of life due to vision loss. No pharmacological therapies are currently approved for DR, excepted the drugs to treat diabetic macular edema such as the anti-VEGF agents or steroids administered by intraocular route. Advancements in research have highlighted the crucial role of early intervention in DR for halting or delaying disease progression. This holds immense significance in enhancing patients' quality of life and alleviating the societal burden associated with medical care costs. The non-proliferative stage represents the early phase of DR. In comparison to the proliferative stage, pathological changes primarily manifest as microangiomas and hemorrhages, while at the cellular level, there is a loss of pericytes, neuronal cell death, and disruption of components and functionality within the retinal neuronal vascular unit encompassing pericytes and neurons. Both neurodegenerative and microvascular abnormalities manifest in the early stages of DR. Therefore, our focus lies on the non-proliferative stage of DR and we have initially summarized the mechanisms involved in its development, including pathways such as polyols, that revolve around the pathological changes occurring during this early stage. We also integrate cutting-edge mechanisms, including leukocyte adhesion, neutrophil extracellular traps, multiple RNA regulation, microorganisms, cell death (ferroptosis and pyroptosis), and other related mechanisms. The current status of drug therapy for early-stage DR is also discussed to provide insights for the development of pharmaceutical interventions targeting the early treatment of DR.

N6-methyladenosine (m6A) methylation in kidney diseases: Mechanisms and therapeutic potential.

The N6-methyladenosine (m6A) modification is regulated by methylases, commonly referred to as "writers," and demethylases, known as "erasers," leading to a dynamic and reversible process. Changes in m6A levels have been implicated in a wide range of cellular processes, including nuclear RNA export, mRNA metabolism, protein translation, and RNA splicing, establishing a strong correlation with various diseases. Both physiologically and pathologically, m6A methylation plays a critical role in the initiation and progression of kidney disease. The methylation of m6A may also facilitate the early diagnosis and treatment of kidney diseases, according to accumulating research. This review aims to provide a comprehensive overview of the potential role and mechanism of m6A methylation in kidney diseases, as well as its potential application in the treatment of such diseases. There will be a thorough examination of m6A methylation mechanisms, paying particular attention to the interplay between m6A writers, m6A erasers, and m6A readers. Furthermore, this paper will elucidate the interplay between various kidney diseases and m6A methylation, summarize the expression patterns of m6A in pathological kidney tissues, and discuss the potential therapeutic benefits of targeting m6A in the context of kidney diseases.

Changes in the Strength and Leaching Characteristics of Steel Slag-Oil Shale Residue-Based Filling Paste in a Complex Erosive Environment.

Our research group prepared a new filling paste consisting of steel slag-oil shale residue and no admixtures. It was used as the research object to explore the combined effect of chloride and dry-wet cycling-driven erosion on the long-term stability of a cemented filling paste made of total solid wastes. Macroscopic experiments and microscopic analyses methods were employed. The influence of solutions with different mass fractions of chloride salts and different cycling periods on the uniaxial compressive strength and toxicity of the steel slag-oil shale residue-based filling paste was studied, and the deterioration mechanisms of the steel slag-oil shale residue-based filling paste under combined erosion from chloride and dry-wet cycling were investigated. The test results showed that in the same cycling conditions, the strength of the steel slag-oil shale residue-based filling paste increased first with the increase in the mass fraction of the chloride solution and then decreased with the increase in the mass fraction of the chloride solution after reaching the peak value; the leached concentrations of heavy metal ions decreased with increasing chloride salt mass fraction. With an increase in the number of dry-wet cycles, the compressive strength of the specimens in the chloride salt solution with a mass fraction of 0 (pure water) first increases and then tends to be stable. The strength of samples in 5% and 10% chloride salt solutions increased first and then decreased with an increase in the number of dry-wet cycles. The leached concentrations of heavy metal ions from the samples in all three solutions first decreased and then stabilized. The prehydration products of the steel slag-oil shale residue-based filling paste were C-S-H gels, AFt and Friedel's salt, and these increased with increasing chloride salt mass fraction and the number of dry-wet cycles. However, the hydration reactions of the samples in the 0% chloride solution nearly stopped in the later stages of cycling, and the samples in 5% and 10% chloride salt solutions developed local cracks due to the accumulation of hydration products. The results showed that the number of dry-wet cycles and the chloride salt mass fraction affected the strength and leaching characteristics of the steel slag-oil shale residue-based filling paste by changing the type and amount of erosion products. The test results provide a scientific basis for the promotion and application of backfilling pastes made from total solid wastes.

Jinlida granules combined with metformin improved the standard-reaching rate of blood glucose and clinical symptoms of patients with type 2 diabetes: secondary analysis of a randomized controlled trial.

Background: Previous studies found that Jinlida granules could significantly reduce blood glucose levels and enhance the low-glucose action of metformin. However, the role of Jinlida in the standard-reaching rate of blood glucose and improving clinical symptoms has yet to be studied. We aimed to elaborate on the efficacy of Jinlida in type 2 diabetes (T2D) patients who experience clinical symptoms based on secondary analysis of a randomized controlled trial. Methods: Data were analyzed from a 12-week, randomized, placebo-controlled study of Jinlida. The standard-reaching rate of blood glucose, the symptom disappearance rate, the symptom improvement rate, the efficacy of single symptoms, and the total symptom score were evaluated. The correlation between HbA1c and the improvement of clinical symptoms was analyzed. Results: For 12 weeks straight, 192 T2D patients were randomly assigned to receive either Jinlida or a placebo. The treatment group showed statistically significant differences in the standard-reaching rate of HbA1c < 6.5% (p = 0.046) and 2hPG (< 10 mmol/L, 11.1 mmol/L) (p < 0.001), compared with the control group. The standard-reaching rate of HbA1c < 7% (p = 0.06) and FBG < 7.0 mmol/L (p = 0.079) were not significantly different between the treatment and control groups. Five symptoms exhibited a statistical difference in symptom disappearance rate (p < 0.05). All the symptoms exhibited a significant difference in symptom improvement rate (p < 0.05). The mean change in total symptom score from baseline to week 12 was -5.45 ± 3.98 in the treatment group and -2.38 ± 3.11 in the control group, with statistically significant differences (p < 0.001). No significant correlations were noted between symptom improvement and HbA1c after 12 weeks of continuous intervention with Jinlida granules or placebo. Conclusion: Jinlida granules can effectively improve the standard-reaching rate of blood glucose and clinical symptoms of T2D patients, including thirst, fatigue, increased eating with rapid hungering, polyuria, dry mouth, spontaneous sweating, night sweat, vexing heat in the chest, palms, and soles, and constipation. Jinlida granules can be used as an effective adjuvant treatment for T2D patients who experience those symptoms.

Axonal transport deficits in the pathogenesis of diabetic peripheral neuropathy.

Diabetic peripheral neuropathy (DPN) is a chronic and prevalent metabolic disease that gravely endangers human health and seriously affects the quality of life of hyperglycemic patients. More seriously, it can lead to amputation and neuropathic pain, imposing a severe financial burden on patients and the healthcare system. Even with strict glycemic control or pancreas transplantation, peripheral nerve damage is difficult to reverse. Most current treatment options for DPN can only treat the symptoms but not the underlying mechanism. Patients with long-term diabetes mellitus (DM) develop axonal transport dysfunction, which could be an important factor in causing or exacerbating DPN. This review explores the underlying mechanisms that may be related to axonal transport impairment and cytoskeletal changes caused by DM, and the relevance of the latter with the occurrence and progression of DPN, including nerve fiber loss, diminished nerve conduction velocity, and impaired nerve regeneration, and also predicts possible therapeutic strategies. Understanding the mechanisms of diabetic neuronal injury is essential to prevent the deterioration of DPN and to develop new therapeutic strategies. Timely and effective improvement of axonal transport impairment is particularly critical for the treatment of peripheral neuropathies.

The crucial role and mechanism of insulin resistance in metabolic disease.

Insulin resistance (IR) plays a crucial role in the development and progression of metabolism-related diseases such as diabetes, hypertension, tumors, and nonalcoholic fatty liver disease, and provides the basis for a common understanding of these chronic diseases. In this study, we provide a systematic review of the causes, mechanisms, and treatments of IR. The pathogenesis of IR depends on genetics, obesity, age, disease, and drug effects. Mechanistically, any factor leading to abnormalities in the insulin signaling pathway leads to the development of IR in the host, including insulin receptor abnormalities, disturbances in the internal environment (regarding inflammation, hypoxia, lipotoxicity, and immunity), metabolic function of the liver and organelles, and other abnormalities. The available therapeutic strategies for IR are mainly exercise and dietary habit improvement, and chemotherapy based on biguanides and glucagon-like peptide-1, and traditional Chinese medicine treatments (e.g., herbs and acupuncture) can also be helpful. Based on the current understanding of IR mechanisms, there are still some vacancies to follow up and consider, and there is also a need to define more precise biomarkers for different chronic diseases and lifestyle interventions, and to explore natural or synthetic drugs targeting IR treatment. This could enable the treatment of patients with multiple combined metabolic diseases, with the aim of treating the disease holistically to reduce healthcare expenditures and to improve the quality of life of patients to some extent.

The impact of oxidative stress-induced mitochondrial dysfunction on diabetic microvascular complications.

Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycaemia, with absolute insulin deficiency or insulin resistance as the main cause, and causes damage to various target organs including the heart, kidney and neurovascular. In terms of the pathological and physiological mechanisms of DM, oxidative stress is one of the main mechanisms leading to DM and is an important link between DM and its complications. Oxidative stress is a pathological phenomenon resulting from an imbalance between the production of free radicals and the scavenging of antioxidant systems. The main site of reactive oxygen species (ROS) production is the mitochondria, which are also the main organelles damaged. In a chronic high glucose environment, impaired electron transport chain within the mitochondria leads to the production of ROS, prompts increased proton leakage and altered mitochondrial membrane potential (MMP), which in turn releases cytochrome c (cyt-c), leading to apoptosis. This subsequently leads to a vicious cycle of impaired clearance by the body's antioxidant system, impaired transcription and protein synthesis of mitochondrial DNA (mtDNA), which is responsible for encoding mitochondrial proteins, and impaired DNA repair systems, contributing to mitochondrial dysfunction. This paper reviews the dysfunction of mitochondria in the environment of high glucose induced oxidative stress in the DM model, and looks forward to providing a new treatment plan for oxidative stress based on mitochondrial dysfunction.

Effects of antioxidants on diabetic kidney diseases: mechanistic interpretations and clinical assessment.

Diabetic kidney disease (DKD) is more prevalent with an increase in diabetes mellitus. Oxidative stress is a major factor in the occurrence and progression of DKD. Defending against oxidative stress and restoring antioxidant defense might be key to preventing and treating DKD. The purpose of this article is to provide an explanation of how oxidative stress affects DKD, conduct a systematic review and meta-analysis on DKD, and examine the effect of antioxidants on the disease. An analysis of 19 randomized controlled trials showed that the use of antioxidants could reduce UAE (albumin excretion rate) in patients with DKD (SMD: - 0.31; 95% CI [- 0.47, - 0.14], I2 = 0%), UACR (urine albumin/creatinine ratio) (SMD: - 0.60; 95% CI [- 1.15, - 0.06], I2 = 89%), glycosylated hemoglobin (hbA1c) (MD: - 0.61; 95% CI [- 1.00, - 0.21], I2 = 93%) and MDA (malonaldehyde) (SMD:-1.05; 95% CI [- 1.87, - 0.23], I2 = 94%), suggesting that antioxidants seemed to have therapeutic effects in patients with DKD, especially in reducing proteinuria and hbA1c. The purpose of this study is to provide new targets and ideas for drug research and clinical treatment of DKD.

Model exploration for discovering COVID-19 targeted traditional Chinese medicine.

In terms of treatment, a particularly targeted drug is needed to combat the COVID-19 pandemic. Although there are currently no specific drugs for COVID-19, traditional Chinese medicine(TCM) is clearly effective. It is recommended that through data analysis and mining of TCM cases (expert experience) and population evidence (RCT and cohort studies), core prescriptions for various efficacy can be obtained. Starting from a multidimensional model of regulating immunity, improving inflammation, and protecting multiple organs, this paper constructs a multidimensional model of targeted drug discovery, integrating molecular, cellular, and animal efficacy evaluation. Through functional activity testing, biophysical detection of compound binding to target proteins, multidimensional pharmacodynamic evaluation systems of cells (Vero E6, Vero, Vero81, Huh7, and caca2) and animals (mice infected with the new coronavirus, rhesus macaques, and hamsters), the effectiveness of effective preparations was evaluated, and various efficacy effects including lung moisturizing, dehumidification and detoxification were obtained. Using modern technology, it is now possible to understand how the immune system is controlled, how inflammation is reduced, and how various organs are protected. Complete early drug characterization and finally obtain effective targeted TCM. This article provides a demonstration resource for the development of new drugs specifically for TCM.

The critical role of the Hippo signaling pathway in kidney diseases.

The Hippo signaling pathway is involved in cell growth, proliferation, and apoptosis, and it plays a key role in regulating organ size, tissue regeneration, and tumor development. The Hippo signaling pathway also participates in the occurrence and development of various human diseases. Recently, many studies have shown that the Hippo pathway is closely related to renal diseases, including renal cancer, cystic kidney disease, diabetic nephropathy, and renal fibrosis, and it promotes the transformation of acute kidney disease to chronic kidney disease (CKD). The present paper summarizes and analyzes the research status of the Hippo signaling pathway in different kidney diseases, and it also summarizes the expression of Hippo signaling pathway components in pathological tissues of kidney diseases. In addition, the present paper discusses the positive therapeutic significance of traditional Chinese medicine (TCM) in regulating the Hippo signaling pathway for treating kidney diseases. This article introduces new targets and ideas for drug development, clinical diagnosis, and treatment of kidney diseases.

Naoxintong capsule delay the progression of diabetic kidney disease: A real-world cohort study.

Introduction: Diabetic kidney disease (DKD) is a severe and growing health problem, associated with a worse prognosis and higher overall mortality rates than non-diabetic renal disease. Chinese herbs possess promising clinical benefits in alleviating the progression of DKD due to their multi-target effect. This real-world retrospective cohort trial aimed to investigate the efficacy and safety of Naoxintong (NXT) capsules in the treatment of DKD. Our study is the first real-world study (RWS) of NXT in the treatment of DKD based on a large database, providing a basis for clinical application and promotion. Methods: The data was collected from Tianjin Healthcare and Medical Big Data Platform. Patients with DKD were enrolled from January 1, 2011, to March 31, 2021. NXT administration was defined as the exposure. The primary outcome was the change in estimated glomerular filtration rate (eGFR). We employed the propensity score matching (PSM) method to deal with confounding factors. Results: A total of 1,798 patients were enrolled after PSM, including 899 NXT users (exposed group) and 899 non-users (control group). The eGFR changes from baseline to the end of the study were significantly different in the exposed group compared to the control group (-1.46 ± 21.94 vs -5.82 ± 19.8 mL/(min·1.73m2), P< 0.01). Patients in the NXT group had a lower risk of composite renal outcome event (HR, 0.71; 95%CI, 0.55 to 0.92; P = 0.009) and deterioration of renal function (HR, 0.74; 95% CI, 0.56 to 0.99; P = 0.039). Conclusion: NXT can significantly slow the decline of eGFR and reduce the risk of renal outcomes. However, large cohort studies and RCTs are needed to further confirm our results.

The critical role of dysregulated autophagy in the progression of diabetic kidney disease.

Diabetic kidney disease (DKD) is one of the major public health problems in society today. It is a renal complication caused by diabetes mellitus with predominantly microangiopathy and is a major cause of end-stage renal disease (ESRD). Autophagy is a metabolic pathway for the intracellular degradation of cytoplasmic products and damaged organelles and plays a vital role in maintaining homeostasis and function of the renal cells. The dysregulation of autophagy in the hyperglycaemic state of diabetes mellitus can lead to the progression of DKD, and the activation or restoration of autophagy through drugs is beneficial to the recovery of renal function. This review summarizes the physiological process of autophagy, illustrates the close link between DKD and autophagy, and discusses the effects of drugs on autophagy and the signaling pathways involved from the perspective of podocytes, renal tubular epithelial cells, and mesangial cells, in the hope that this will be useful for clinical treatment.

Efficacy and safety of a Chinese herbal formula Maxing Ganshi Decoction in children with community-acquired pneumonia: A randomized, double-blind, placebo-controlled, multicenter trial.

Background: As one of the most commonly used Chinese medicine formula in the manage of respiratory diseases, Maxing Ganshi Decoction (MGD) has been demonstrated to improve the clinical symptoms of pneumonia. To evaluate the efficacy and safety of MGD in treating children with community-acquired pneumonia (CAP), we conducted the clinical trial. Methods: A randomized, double-blind, placebo-controlled, multicenter trial was conducted in 3 study sites in Tianjin, China. MDG or placebo were randomly given to patients aged 3-6 years with onset of CAP within 48 h. Changes in disease efficacy during the study period (which was measured as recovery, significant effect, improvement and no effect) was evaluated as the primary outcome. Time from enrollment to fever resolution was assessed as the secondary outcome. The adverse event was analyzed as safety evaluation. Results: A total of 71 patients (36 in MGD and 35 in placebo) were randomized and completed the whole study. The patient demographics and other characteristics at baseline were similar between the 2 groups (p > 0.05). After 10 days of intervention, the proportion of recovered and significant effective patients was increased significantly in the MGD group (34.85% [95% CI, 12.44%-57.26%]; p < 0.05) compared with the control group. Besides, the symptom score of the MGD group was lowered significantly (p < 0.001). The estimated time to fever resolution in the MGD group was also reduced compared with the control group (p < 0.05). During the whole study, no side effects were observed in both MGD and control groups. Conclusion: MGD was effective in improving disease efficacy, clinical symptoms and reducing time to fever resolution in patients with childhood CAP, which suggested that MGD may be used as an alternative therapy in the treatment of childhood CAP. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=5612, identifier 13003955.

Exploring the Regulation of Jiangtang Tiaozhi Formula on the Biological Network of Obese T2DM Complicated With Dyslipidemia Based on Clinical Transcriptomics.

Objective: To use systems biology to explore the biomolecular network mechanism of the Jiangtang Tiaozhi Recipe (JTTZR) in the intervention of obese Type 2 diabetes (T2DM) patients with dyslipidemia. Methods: Twelve patients with obese type 2 diabetes mellitus and dyslipidemia (traditional Chinese medicine syndrome differentiation was excess heat syndrome of the stomach and intestines) were treated with JTTZR for 24 weeks, and 12 patients were included in the healthy control group. First, blood samples from 6 patients in each group (disease group before treatment, disease group after treatment, and healthy control group) were collected for RNA microarray analysis. Quantitative polymerase chain reaction (qPCR) was used to validate these target lncRNAs and mRNAs. Finally, a detailed analysis of the differences in the disease group before treatment vs. the healthy control group and the disease group after treatment vs. the disease group before treatment was undertaken. In addition, we focused on disease-related pathways and analyzed the correlation between the differential expression of target lncRNAs and clinical indicators. Results: (1) Disease group before treatment vs. healthy control group: There were 557 up-regulated lncRNAs, 273 down-regulated lncRNAs, 491 up-regulated mRNAs, and 1639 down-regulated mRNAs. GO analysis and pathway analysis showed that T2DM may be related to cell proliferation in the forebrain, post-embryonic organ development, calcium signaling pathway. qPCR validation showed that the expression of XLOC-005590 and HNF1A-AS1 as target lncRNAs increased, and this was verified by gene chip analysis. (2) Disease group after treatment vs. disease group before treatment: 128 lncRNAs were upregulated, 32 lncRNAs were downregulated, 45 mRNAs were upregulated, and 140 mRNAs were downregulated. GO analysis and pathway analysis showed that JTTZR may treat T2DM through endosome transport, the insulin signaling pathway, and glycine, serine, and threonine metabolism. qPCR validation showed that in the healthy control group, XLOC_005590 was upregulated, whereas the downstream gene (ECI2) was downregulated in the disease group before treatment. However, after 24 weeks of intervention with JTTZR, XLOC_005590 was downregulated and ECI2 was upregulated compared with the disease group before treatment (0 weeks) (P <0.05). Conclusion: JTTZR may interfere in patients with obese T2DM with dyslipidemia by regulating pathways such as fatty acid degradation, glycolysis/gluconeogenesis, and pyruvate metabolism.

Mechanism of Cornus Officinalis in Treating Diabetic Kidney Disease Based on Network Pharmacology.

Diabetic kidney disease (DKD), one of the most important diabetic complications, is a great clinical challenge. It still lacks proper therapeutic strategies without side effects due to the complex pathological mechanisms. Cornus officinalis (CO) is a common traditional Chinese medicine, which has been used in the treatment of DKD and takes beneficial effects in therapy. However, the mechanism of CO in treating DKD is not clear yet. In this study, network pharmacology was applied to illustrate the potential mechanism of CO and the interaction between targets of CO and targets of disease. First, the active ingredients of CO and related targets were screened from the online database. Second, the intersection network between CO and disease was constructed, and protein-protein interaction analysis was done. Third, GO and KEGG analysis were employed to figure out the key targets of CO. Finally, molecular docking was carried out in the software SYBYL to verify the effectiveness of the ingredients and targets selected. According to GO and KEGG analysis, drug metabolism-cytochrome P450, sphingolipid signaling pathway, HIF-1 signaling pathway, TGF-beta signaling pathway, cGMP-PKG signaling pathway, estrogen signaling pathway, and TNF signaling pathway were most closely related to the pathogenesis of DKD. Moreover, NOS3, TNF, ROCK1, PPARG, KDR, and HIF1A were identified as key targets in regulating the occurrence and development of the disease. This study provides evidence to elucidate the mechanism of CO comprehensively and systematically and lays the foundation for further research on CO.

Modulation of Gut Microbiota and Metabolites by Berberine in Treating Mice With Disturbances in Glucose and Lipid Metabolism.

Introduction: Glucose and lipid metabolism disturbances has become the third major disease after cancer and cardio-cerebrovascular diseases. Emerging evidence shows that berberine can effectively intervene glucose and lipid metabolism disturbances, but the underlying mechanisms of this remain unclear. To investigate this issue, we performed metagenomic and metabolomic analysis in a group of normal mice (the NC group), mice with disturbances in glucose and lipid metabolism (the MC group) and mice with disturbances in glucose and lipid metabolism after berberine intervention (the BER group). Result: Firstly, analysis of the clinical indicators revealed that berberine significantly improved the blood glucose and blood lipid of the host. The fasting blood glucose level decreased by approximately 30% in the BER group after 8 weeks and the oral glucose tolerance test showed that the blood glucose level of the BER group was lower than that of the MC group at any time. Besides, berberine significantly reduced body weight, total plasma cholesterol and triglyceride. Secondly, compared to the NC group, we found dramatically decreased microbial richness and diversity in the MC group and BER group. Thirdly, LDA effect size suggested that berberine significantly altered the overall gut microbiota structure and enriched many bacteria, including Akkermansia (p < 0.01), Eubacterium (p < 0.01) and Ruminococcus (p < 0.01). Fourthly, the metabolomic analysis suggested that there were significant differences in the metabolomics signature of each group. For example, isoleucine (p < 0.01), phenylalanine (p < 0.05), and arbutin (p < 0.05) significantly increased in the MC group, and berberine intervention significantly reduced them. The arbutin content in the BER group was even lower than that in the NC group. Fifthly, by combined analysis of metagenomics and metabolomics, we observed that there were significantly negative correlations between the reduced faecal metabolites (e.g., arbutin) in the BER group and the enriched gut microbiota (e.g., Eubacterium and Ruminococcus) (p < 0.05). Finally, the correlation analysis between gut microbiota and clinical indices indicated that the bacteria (e.g., Eubacterium) enriched in the BER group were negatively associated with the above-mentioned clinical indices (p < 0.05). Conclusion: Overall, our results describe that the changes of gut microbiota and metabolites are associated with berberine improving glucose and lipid metabolism disturbances.

Standards for Collection, Preservation, and Transportation of Fecal Samples in TCM Clinical Trials.

Background: Unlike chemical drugs with a single or a few kinds of active compounds, traditional Chinese medicines (TCMs)uses herbal formulas composed of numerous kinds of chemical constituents. Therefore, TCM clinical trials require unique and stricter standards for collecting, preserving, and transporting fecal samples than those used for chemical drugs. Unfortunately, there are no special standards for processing fecal samples in TCM clinical trials. Methods: We invited interdisciplinary experts within TCM clinical trials and gut microbiome research to help formulate this standard. After more than a year's in-depth discussion and amendments, we achieved a standard via expert interviews, literature research, questionnaire surveys, and public opinion solicitation. This standard has been reviewed and approved by the Standards Office of China of the Association of Chinese medicine. Results: We established a sample information processing method prior to TCM clinical sample collection, which is adapted to the unique features of TCM. The method formulates detailed processing requirements for TCM information in addition to the factors that may disturb the gut microbiome. We also constructed a set of methods for collecting, preserving, and transporting fecal samples that meet the characteristics of TCM. These methods formulate detailed operating specifications on the collection approaches, storage conditions, transportation requirements, and management of fecal samples. Conclusions: This standard guides the information processing prior to sample collection and the standard operating procedures for the collection, preservation, and transportation of fecal samples in TCM clinical trials, which also can be used as a reference by clinicians and researchers in modern medicines.