Clinical efficacy of Jingyin granules, a Chinese patent medicine, in treating patients infected with coronavirus disease 2019.

BACKGROUND: Jingyin granules (JY), one patented Chinese herbal formula, have been advised for treating coronavirus disease 2019 (COVID-19) in China. As of now, the safety and effectiveness of JY in treating COVID-19 patients were still to be evaluated. PURPOSE: To investigate the safety and clinical effectiveness of JY in treating mild COVID-19 patients. STUDY DESIGN: We carried out a prospective cohort study, as the highly infectious COVID-19 omicron variant ranged in Shanghai (ClinicalTrial.gov registration number: ChiCTR2200058692). METHODS: Participants infected with COVID-19, who were diagnosed as mild cases, were assigned to receive either JY (JY group) or traditional Chinese medicine placebo (placebo group) orally for 7 days. The primary clinical indicators were the RNA negative conversion rate (NCR) and the incidence of severe cases. The secondary clinical indicators were the negative conversion time (NCT), inpatient length of stay (ILOS), and the disappearance rates of clinical symptoms. RESULTS: Nine hundred participants were recruited in this clinical trial study, and 830 patients met the eligibility criteria. Seven hundred and ninety-one patients, accomplished the following-up assessment, including 423 cases of JY group and 368 cases of placebo group. NCR in JY group at 7-day posttreatment was considerably greater compared with placebo group (89.8% [380/423] vs 82.6% [304/368], P = 0.003). None of the patients with mild COVID-19 developed into severe cases. The median NCT of SARS-CoV-2 and ILOS in JY group were lesser than that in placebo group (4.0 [3.0,6.0]vs 5.0 [4.0,7.0] days, P < 0.001; 6.0 [4.0, 8.0] vs 7.0 [5.0, 9.0] days, P < 0.001). In both groups, the obvious improvement in clinical symptoms was observed, but the difference was not significant. In the subgroup of age ≤ 60 years, JY promoted SARS-CoV-2 RNA negative conversion (HR=1.242; 95% CI: 1.069-1.444, P < 0.001). No patients in both groups were reported as the case of serious adverse event. CONCLUSION: JY maybe the potential medicine for treating mild COVID-19 patients, which had beneficial effects on increasing NCR, and shortening NCT and ILOS.

Traditional Chinese Medicine JingYinGuBiao Formula Therapy Improves the Negative Conversion Rate of SARS-CoV2 in Patients with Mild COVID-19.

Background: Traditional Chinese Medicine (TCM) JingYinGuBiao formula (JYGB) was recommended by the Expert consensus on Traditional Chinese Medicine diagnosis and treatment of COVID-19 infection in Shanghai. We evaluated the safety and efficacy of JYGB in treating mild COVID-19 patients. Methods: A prospective, double-blind, randomized, controlled trial was conducted (ClinicalTrial.gov registration number: ChiCTR2200058695). A total of 885 patients were randomized into the treatment group (administration of JYGB,n=508) or the control group (administration of TCM placebo, n=377) with 7-day treatment. The primary outcomes were the negative conversion rate and negative conversion time of SARS-CoV2 RNA. Secondary outcomes included the hospitalized days and symptom improvement. Results: A total of 490 and 368 patients in the treatment and control groups completed the study. The cumulative negative conversion rates at 2 days, 3 days, 4 days, and 6 days post randomization in the treatment group were all markedly higher than those in the control group (13.88% vs. 9.24%, P=0.04; 32.24% vs. 16.58%, P<0.001; 51.43% vs. 36.14%, P <0.001; 77.76% vs. 69.84%, P=0.008). Compared with the control group, after JYGB treatment, the median negative conversion time (4.0 [3.0-6.0] vs. 5.0 [4.0-7.0] days, P<0.001) and hospitalized days (6.0 [4.0-8.0] vs. 7.0 [5.0-9.0] days, P<0.001) were reduced. While the symptoms were improved, there were no significant differences in symptom disappearance rates between both groups. In addition, further sub-group analysis showed that for patients with interval time ≤4 days or patients≤ 60 years, the clinical effects of JYGB were more remarkable with an increase in cumulative negative conversion rates, a decrease in negative conversion time and hospitalized days. JYGB was well tolerated without any severe side effects. Conclusion: JYGB, a TCM prescription, improves the negative conversion rate of SARS-CoV2 in mild COVID-19 patients.

BCAA Supplementation in Mice with Diet-induced Obesity Alters the Metabolome Without Impairing Glucose Homeostasis.

Circulating branched chain amino acid (BCAA) levels are elevated in obese humans and genetically obese rodents. However, the relationship of BCAAs to insulin resistance in diet-induced obese mice, a commonly used model to study glucose homeostasis, is still ill-defined. Here we examined how high-fat high-sucrose (HFHS) or high-fat diet (HFD) feeding, with or without BCAA supplementation in water, alters the metabolome in serum/plasma and tissues in mice and whether raising circulating BCAA levels worsens insulin resistance and glucose intolerance. Neither HFHS nor HFD feeding raised circulating BCAA levels in insulin-resistant diet-induced obese mice. BCAA supplementation raised circulating BCAA and branched-chain α-keto acid levels and C5-OH/C3-DC acylcarnitines (AC) in muscle from mice fed an HFHS diet or HFD, but did not worsen insulin resistance. A set of short- and long-chain acyl CoAs were elevated by diet alone in muscle, liver, and white adipose tissue (WAT), but not increased further by BCAA supplementation. HFD feeding reduced valine and leucine oxidation in WAT but not in muscle. BCAA supplementation markedly increased valine oxidation in muscle from HFD-fed mice, while leucine oxidation was unaffected by diet or BCAA treatment. Here we establish an extensive metabolome database showing tissue-specific changes in mice on 2 different HFDs, with or without BCAA supplementation. We conclude that mildly elevating circulating BCAAs and a subset of ACs by BCAA supplementation does not worsen insulin resistance or glucose tolerance in mice. This work highlights major differences in the effects of BCAAs on glucose homeostasis in diet-induced obese mice versus data reported in obese rats and in humans.

68Ga-NOTA PET imaging for gastric emptying assessment in mice.

BACKGROUND: Positron emission tomography (PET) has the potential for visualization and quantification of gastric emptying (GE). The traditional Chinese medicine (TCM) has been recognized promising for constipation. This study aimed to establish a PET imaging method for noninvasive GE measurement and to evaluate the efficacy of a TCM on delayed GE caused by constipation using PET imaging. METHODS: [68Ga]Ga-NOTA was synthesized as the tracer and sesame paste with different viscosity were selected as test meals. The dynamic PET scans were performed after [68Ga]Ga-NOTA mixed with test meals were administered to normal mice. Two methods were utilized for the quantification of PET imaging. A constipation mouse model was treated with maren chengqi decoction (MCD), and the established PET imaging scans were performed after the treatment. RESULTS: [68Ga]Ga-NOTA was synthesized within 20 min, and its radiochemical purity was > 95%. PET images showed the dynamic process of GE. %ID/g, volume, and total activity correlated well with each other. Among which, the half of GE time derived from %ID/g for 4 test meals were 3.92 ± 0.87 min, 13.1 ± 1.25 min, 17.8 ± 1.31 min, and 59.7 ± 3.11 min, respectively. Constipation mice treated with MCD showed improved body weight and fecal conditions as well as ameliorated GE measured by [68Ga]Ga-NOTA PET. CONCLUSIONS: A PET imaging method for noninvasive GE measurement was established with stable radiotracer, high image quality, and reliable quantification methods. The efficacy of MCD on delayed GE was demonstrated using PET.

PET evaluation of light-induced modulation of microglial activation and GLP-1R expression in depressive rats.

Light therapy has been accepted as a promising therapeutic choice for depression. Positron emission tomography (PET) combined with specific radiotracers has great benefits for revealing pathogenesis and developing therapeutics. This study aimed to investigate the influences of light therapy on microglial activation and glucagon-like peptide-1 receptor (GLP-1R) expression in the brain of depressive rats using [18F]DPA-714 and [18F]exendin-4 PET. The results showed that chronic unpredictable mild stress (CUMS)-induced depressive rats had poorer performance in behavioral tests compared to normal rats (p < 0.05) and the depressive-like behavior could be ameliorated by light therapy. Besides, depressive rats had significantly higher [18F]DPA-714 uptake and lower [18F]FDG uptake compare to normal rats in 11 and 9 regions of interest (ROIs) of the brain, respectively (p < 0.05). After 5 weeks of light therapy, higher [18F]FDG and [18F]exendin-4 uptake was observed in most ROIs of light therapy-treated depressive rats compared to untreated depressive rats (p < 0.05) and no significant differences existed in [18F]DPA-714 uptake between the two groups. This study demonstrated that light therapy can ameliorate depressive-like behavior, improve glucose metabolism, and halt the decline of brain GLP-1R expression of depressive rats, but have no effects on microglial activation caused by CUMS. Besides, this study validated that [18F]DPA-714 and [18F]exendin-4 PET have the potential for noninvasive evaluation of microglial activation and GLP-1R expression in the brain of depression.

[Characteristics of Phytoplankton Community and Its Relationship with Environmental Factors in Different Regions of Yilong Lake, Yunnan Province, China].

Yilong Lake, a shallow, plateau lake, is the ninth largest water body in the Yunnan Province, China. In order to figure out the characteristics of phytoplankton communities in different regions of this lake, the phytoplankton and environmental factors in the west region, east region, and in a submerged macrophytes restoration demonstration region were monthly investigated and analyzed from August 2013 to July 2014. The results showed that the habitats in different regions were spatially heterogeneous. Total nitrogen (TN), total phosphorus (TP), ammonia nitrogen (NH4+-N), five-day biochemical oxygen demand (BOD5), transparency (SD), turbidity (Turb.), and electrical conductivity (EC) had no significant differences between the demonstration region and the west region, but these two regions showed significant differences in comparison with the east region (P<0.05). The largest phytoplankton density was Cyanophyta and the dominant species in the three regions were different. Mersmopedia tenuissima had the highest dominance in the west region; Cylindrospermopsis raciborskii and Pseudanabaena limntica were the most dominant taxa in the east region; while Merismopedia tenuissima and Anabaenopsis sp. were dominant in the O. uminata restoration demonstration region. PCoA compared the ß diversity of phytoplankton communities in the three different regions based on the entire year investigations. It was found that the community structures of the west region and O. uminata restoration demonstration region were similar (P>0.05), but they were significantly different from the community from the east region (P<0.01). Redundant analysis (RDA) showed that TN, TP, BOD5, and SD were the main environmental factors affecting the distribution of phytoplankton community in Yilong Lake. In addition, NH4+-N, EC, permanganate index, and pH also have a certain effect on the phytoplankton community.

Catalytic hydrothermal upgrading of crude bio-oils produced from different thermo-chemical conversion routes of microalgae.

This study presents experimental results that compare the use of hydrothermal liquefaction (HTL), alcoholysis (Al), pyrolysis (Py) and hydropyrolysis (HPy) for the production of bio-oil from a microalga (Chlorella pyrenoidosa) and the catalytic hydrothermal upgrading of crude bio-oils produced by these four conversion routes. The yields and compositions of bio-oil, solid residue, and gases were evaluated and compared. HTL resulted in a bio-oil that has a higher energy density and superior fuel properties, such as thermal and storage stabilities, compared with the other three conversion routes. The N in crude bio-oils produced from Py and HPy is more easily removed than that in the bio-oils produced from HTL and Al. The upgraded bio-oils contain reduced amounts of certain O-containing and N-containing compounds and significantly increased saturated hydrocarbon contents. All of the upgraded bio-oils have a larger fraction boiling below 350°C than their corresponding crude bio-oils.

A rapid UFLC-MS/MS method for simultaneous determination of formononetin, cryptotanshinone, tanshinone IIA and emodin in rat plasma and its application to a pharmacokinetic study of Bu Shen Huo Xue formula.

Bu Shen Huo Xue formula (BSHX) is a traditional Chinese medicine prescription used for clinical treatment of chronic kidney diseases. A rapid and selective Ultra fast liquid chromatography with tandem mass spectrometry (UFLC-MS/MS) method was developed for simultaneous determination of four bioactive components of BSHX including formononetin, cryptotanshinone, tanshinone IIA, and emodin in control and unilateral ureteral obstruction (UUO) model rat plasma for the first time. Atorvastatin was used as the internal standard (IS). Plasma samples were extracted by liquid-liquid extraction with ethyl acetate. The chromatographic separation was carried out on a Shim-pack XR-ODS III column with a gradient mobile phase consisting of acetonitrile and 0.1% formic acid. The detection was performed on a triple-quad tandem mass spectrometer by multiple reaction monitoring (MRM) via electrospray ionization (ESI) source with positive ionization mode for formononetin, cryptotanshinone, tanshinone IIA, and negative mode for emodin. The method was linear for four analytes over the range of investigated concentration with all coefficients of determination (R(2)) greater than 0.9938. The lower limits of quantification (LLOQ) for formononetin, cryptotanshinone, tanshinone IIA, and emodin were defined as 0.3, 0.5, 1.5, and 0.3ng/mL, respectively. The rapid and sensitive method was fully validated and successfully applied to the pharmacokinetic study of formononetin, cryptotanshinone, tanshinone IIA and emodin in rats following oral administration of Bu Shen Huo Xue formula.

[The effect of Gynostemma pentaphyllum (GP) on plasma lipoprotein metabolism and lipoperoxidation lipoprotein in the experimental hyperglycemia rats].

AIM: To study the regulation mechanism of GP on plasma lipoprotein metabolism and To explore its mechanism of anti-lipoperoxidation in the experimental hyperglycemia rats. METHODS: The rats were raised with high fat diet for six weeks,and the model of hyperglycemia was then established. After that, those rats were treated with high or low dose of GP and xuezhikang as a masculine comparison for four weeks. Then, those rat were executed, and detected the plasma TC, TG, LDL-C, HDL-C, GSH-Px, at the same time the SOD, CAT and MDA concentration also be mensurated. RESULTS: The results showed that high and low dose of GP could decrease the concentration of serum LDL-C, cholesterol and triglyceride remarkably and raise the concentration of HDL-C. The activity of GSH-Px, SOD and CAT in GP groups were promoted and the level of MDA was decreased distinctly. CONCLUSION: The GP can therapy the abnormity of serum lipid and has obviously anti-lipoperoxidation affection.