Jin-Zhen oral liquid for pediatric coronavirus disease (COVID-19): A randomly controlled, open-label, and non-inferiority trial at multiple clinical centers.

Background: As the coronavirus disease 2019 (COVID-19) pandemic progressed, especially with the emergence of the Omicron variant, the proportion of infected children and adolescents increased significantly. Some treatment such as Chinese herbal medicine has been administered for COVID-19 as a therapeutic option. Jin-Zhen Oral Liquid is widely used for pediatric acute bronchitis, while the efficacy and safety in the treatment of pediatric COVID-19 are unclear. Methods: We conducted a randomized controlled, open-label, multicenter, non-inferiority clinical study involving hospitalized children with mild to moderate COVID-19. Children eligible for enrollment were randomly assigned in a 1:1 ratio to Jin-Zhen Oral Liquid (the treatment group) and Jinhua Qinggan Granules (the positive control group) and received the respective agent for 14 days, followed by a 14-day follow-up after discontinuation of the treatment. The primary efficacy endpoint was the time to first negative viral testing. The secondary endpoints were the time and rate of major symptoms disappearance, duration of hospitalization, and the proportion of symptoms changed from asymptomatic or mild to moderate or severe/critical illness. In addition, the safety end points of any adverse events were observed. Results: A total of 240 child patients were assigned randomly into the Jin-Zhen Oral Liquid (117 patients) and Jinhua Qinggan Granules (123 patients) groups. There was no significant difference of the baselines in terms of the clinical characteristics and initial symptoms between the two groups. After 14-day administration, the time to first negative viral testing in the Jin-Zhen group (median 6.0 days, 95% CI 5.0-6.0) was significantly shorter compared with the positive control Jinhua Qinggan Granules group (median 7.0 days, 95% CI 7.0-8.0). The time and rate of major clinical symptoms disappearance were comparable to the positive control. The symptom disappearance time of pharyngalgia and hospitalization duration were significantly shortened in the Jin-zhen Oral Liquid group. No participants in either group experienced post-treatment exacerbation to severe or critical illness. No adverse events were observed in the Jin-Zhen Oral Liquid treatment group (0.0%) while 1 patient with adverse events occurred in the positive control Jinhua Qinggan granules group (0.8%). No serious adverse events were observed during the study period in both groups. Conclusion: Jin-Zhen Oral Liquid is safe and effective in the treatment of mild to medium COVID-19 in children. It is non-inferior to Jinhua Qinggan granules in shortening the time to first negative viral testing, the time and rate of major clinical symptoms disappearance, and the hospitalization duration. The results suggest that Jin-Zhen Oral Liquid can be a recommended drug for treatment of pediatric COVID-19 patients.

Comparison of Bisphosphonates Versus Teriparatide in Therapy of the Glucocorticoid-Induced Osteoporosis (GIOP): A Meta-Analysis of Randomized Controlled Trials.

Osteoporosis (OP) is characterized as decreased bone mineral density (BMD) and increased risk of bone fracture. Secondary OP resulting from excess endogenous or exogenous glucocorticoid is defined as glucocorticoid-induced osteoporosis (GIOP). Current therapeutic strategies for GIOP are similar to menopausal osteoporosis, including calcium and vitamin D supplementation, bisphosphonates, and parathyroid hormone (PTH) analogues (teriparatide). Previously, several published meta-analyses compared anti-osteoporotic agents for the menopausal or aging-dependent OP. However, the physiopathologic bone metabolism of GIOP is different. In this study, we investigated the efficacy of BMD enhancement, bone fracture rate and safety of bisphosphonates versus teriparatide in the therapy of GIOP. We searched databases including PubMed, Embase, and the Cochrane Library until Jan 2023, and selected ten random clinical trials (RCT)s that compared the efficacy and/or safety of bisphosphonate versus teriparatide for GIOP patients. Teriparatide therapy increased lumber spinal BMD by 3.96% (95% CI 3.01-4.9%, p<0.00001), 1.23% (95% CI 0.36-2.1%, p=0.006) at total hip, and 1.45% (95% CI 0.31-2.58%, p=0.01) at femoral neck, respectively, compared to bisphosphonates at 18-month therapy for GIOP. Teriparatide also reduced bone fracture especially in vertebral bone (p=0.0001, RR 6.27, 95% CI 2.44-16.07), and increased bone formation and resorption marker levels. There was no difference in the incidence of adverse effects in bisphosphonate and teriparatide groups. Teriparatide showed better performance over bisphosphonate in BMD enhancement, bone fracture reduction, and bone remodeling improvement, without increasing the incidence of adverse effects.

A comparative study of acarbose, vildagliptin and saxagliptin intended for better efficacy and safety on type 2 diabetes mellitus treatment.

As a complicated metabolic disorder, type 2 diabetes mellitus (T2DM) is becoming a major health concern worldwide. Drugs including acarbose, saxagliptin and vildagliptin are applied, but their efficacy is still required to be compared. Therefore, the study aimed to evaluate the efficacy and safety of acarbose, saxagliptin and vildagliptin in the treatment of T2DM. Ninety patients diagnosed with T2DM were treated with acarbose, saxagliptin and vildagliptin, respectively (30 patients for each drug). All patients were examined at 0, 4 and 12 weeks after treatment with vital signs recorded. Fasting blood glucose and blood biochemical indices were analyzed. In addition, fecal samples were taken for microbial macrogenome sequencing and safety evaluation within 12 weeks after treatment. Blood glucose level decreased at 4 and 12 weeks after treatment, and the total cholesterol (TC) and high-density lipoprotein (HDL) levels at 12 weeks were different. Genus abundance of intestinal flora was altered at different time points. Acarbose increased Butyricimonas level first and then decreased it during drug treatment. Saxagliptin increased Megamonas and decreased Turicibacter genus level gradually. Pseudomonas, Klebsiella, Blautia, Faecalibacterium and Roseburia levels fluctuated after Vildagliptin treatment, which increased fasting C-peptide level greater than the other two drugs. Saxagliptin showed higher adverse reactions than acarbose and vildagliptin. Collectively, acarbose, vildagliptin, and saxagliptin can effectively reduce the HbA1c level and affect the intestinal flora distribution in T2DM patients, and the adverse reactions of acarbose and vildagliptin are less than saxagliptin, providing alternative strategies for the treatment of T2DM.

Anticancer Effects of Fufang Yiliu Yin Formula on Colorectal Cancer Through Modulation of the PI3K/Akt Pathway and BCL-2 Family Proteins.

Colorectal cancer (CRC) is one of the most common malignant tumors in China. Fufang Yiliu Yin (FYY) is a traditional Chinese medicine formula used in clinical practice for cancer treatment, but its effectiveness and mechanism of action in human CRC are unclear. In this study, we investigated the antitumor effect of FYY on HCT116 and SW480 human CRC cell lines in vitro and evaluated the underlying molecular mechanism. A subcutaneous xenograft mouse model was used to confirm the antitumor effect in vivo. The components and targets of FYY were collected from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) database. CRC targets were collected via the GeneCards and OMIM databases. Protein-protein interactions were explored using the STRING platform. Cytoscape was used to construct drug-disease-target networks. KEGG and GO analyses were performed to investigate common FYY and CRC targets. FYY significantly inhibited cell proliferation and induced HCT116 and SW480 cell apoptosis. Cell proliferation was blocked at the G0/G1 phase, while cell apoptosis was promoted at the early stage. According to the network pharmacological analysis, quercetin and kaempferol were the most bioactive compounds of FYY. The key targets of FYY were cyclin-D1, MAPK8, and EGFR. GO analysis showed that core targets included the apoptotic signaling pathway, response to steroid hormone, and cellular response to organic cyclic compound. The KEGG pathway analysis showed that FYY may affect CRC through the PI3K/Akt pathway. In vitro, FYY significantly inhibited tumor growth. Pathway analysis confirmed that FYY induced cell apoptosis by modulating PI3K/Akt signaling and BCL-2 family proteins. Hence, our findings indicate that FYY may be a promising adjuvant therapy for CRC.

Identification of compound mutations of SLC12A3 gene in a Chinese pedigree with Gitelman syndrome exhibiting Bartter syndrome-liked phenotypes.

BACKGROUND: Gitelman syndrome is a rare salt-losing renal tubular disorder associated with mutation of SLC12A3 gene, which encodes the Na-Cl co-transporter (NCCT). Gitelman syndrome is characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria, and renin-angiotensin-aldosterone system (RAAS) activation. Different SLC12A3 variants may lead to phenotypic variability and severity. METHODS: In this study, we reported the clinical features and genetic analysis of a Chinese pedigree diagnosed with Gitelman syndrome. RESULTS: The proband exhibited hypokalaemia, hypomagnesemia, metabolic alkalosis, but hypercalciuria and kidney stone formation. The increased urinary calcium excretion made it confused to Bartter syndrome. The persistent renal potassium wasting resulted in renal tubular lesions, and might affect urinary calcium reabsorption and excretion. Genetic analysis revealed mutations of SLC12A3 gene with c.433C > T (p.Arg145Cys), c.1077C > G (p.Asn359Lys), and c.1666C > T (p.Pro556Ser). Potential alterations of structure and function of NCCT protein due to those genetic variations of SLC12A3 are predicted. Interestingly, one sibling of the proband carried the same mutant sites and exhibited similar clinical features with milder phenotypes of hypokalemia and hypomagnesemia, but hypocalciuria rather than hypercalciuria. Family members with at least one wild type copy of SLC12A3 had normal biochemistry. With administration of spironolactone, potassium chloride and magnesium supplement, the serum potassium and magnesium were maintained within normal ranges. CONCLUSIONS: In this study, we identified compound mutations of SLC12A3 associated with varieties of clinical features. Further efforts are needed to investigate the diversity in clinical manifestations of Gitelman syndrome and its correlation with specific SLC12A3 mutations.

Anticancer Effect of Radix Astragali on Cholangiocarcinoma In Vitro and Its Mechanism via Network Pharmacology.

BACKGROUND This study used network pharmacology method and cell model to assess the effects of Radix Astragali (RA) on cholangiocarcinoma (CCA) and to predict core targets and molecular mechanisms. MATERIAL AND METHODS We performed an in vitro study to assess the effect of RA on CCA using CCK8 assay, the Live-Cell Analysis System, and trypan blue staining. The components and targets of RA were analyzed using the Traditional Chinese Medicine Systems Pharmacology database, and genes associated with CCA were retrieved from the GeneCards and OMIM platforms. Protein-protein interactions were analyzed with the STRING platform. The components-targets-disease network was built by Cytoscape. The TIMER database revealed the expression of core targets with diverse immune infiltration levels. GO and KEGG analyses were performed to identify molecular-biology processes and signaling pathways. The predictions were verified by Western blotting. RESULTS Concentration-dependent antitumor activity was confirmed in the cholangiocarcinoma QBC939 cell line treated with RA. RA contained 16 active compounds, with quercetin and kaempferol as the core compounds. The most important biotargets for RA in CCA were caspase 3, MAPK8, MYC, EGFR, and PARP. The TIMER database revealed that the expression of caspase3 and MYC was related with diverse immune infiltration levels of CCA. The results of Western blotting showed RA significantly influenced the expression of the 5 targets that network pharmacology predicted. CONCLUSIONS RA is an active medicinal material that can be developed into a safe and effective multi-targeted anticancer treatment for CCA.