This study aims to explore the mechanism of lung and gut protection by Tanreqing Capsules on the mice infected with influenza virus based on "the lung-gut axis". A total of 110 C57BL/6J mice were randomized into control group, model group, oseltamivir group, and low-and high-dose Tanreqing Capsules groups. Ten mice in each group underwent body weight protection experiments, and the remaining 12 mice underwent experiments for mechanism exploration. Mice were infected with influenza virus A/Puerto Rico/08/1934(PR8) via nasal inhalation for the modeling. The lung tissue was collected on day 3 after gavage, and the lung tissue, colon tissue, and feces were collected on day 7 after gavage for subsequent testing. The results showed that Tanreqing Capsules alleviated the body weight reduction and increased the survival rate caused by PR8 infection. Compared with model group, Tanreqing Capsules can alleviate the lung injury by reducing the lung index, alleviating inflammation and edema in the lung tissue, down-regulating viral gene expression at the late stage of infection, reducing the percentage of neutrophils, and increasing the percentage of T cells. Tanreqing Capsules relieved the gut injury by restoring the colon length, increasing intestinal lumen mucin secretion, alleviating intestinal inflammation, and reducing goblet cell destruction. The gut microbiota analysis showed that Tanreqing Capsules increased species diversity compared with model group. At the phylum level, Tanreqing Capsules significantly increased the abundance of Firmicutes and Actinobacteria, while reducing the abundance of Bacteroidota and Proteobacteria to maintain gut microbiota balance. At the genus level, Tanreqing Capsules significantly increased the abundance of unclassified＿f＿Lachnospiraceae while reducing the abundance of Bacteroides, Eubacterium, and Phocaeicola to maintain gut microbiota balance. In conclusion, Tanreqing Capsules can alleviate mouse lung and gut injury caused by influenza virus infection and restore the balance of gut microbiota. Treating influenza from the lung and gut can provide new ideas for clinical practice.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Lung/metabolism* ; Mice, Inbred C57BL ; Capsules ; Orthomyxoviridae Infections/virology* ; Gastrointestinal Microbiome/drug effects* ; Male ; Humans ; Female ; Influenza A virus/physiology* ; Influenza, Human/virology*

Extensive studies have identified potential adverse effects on semen quality of obesity, based on body mass index, but the association between body fat distribution, a more relevant indicator for obesity, and semen quality remains less clear. We conducted a longitudinal study of 4304 sperm donors from the Guangdong Provincial Human Sperm Bank (Guangzhou, China) during 2017-2021. A body composition analyzer was used to measure total and local body fat percentage for each participant. Generalized estimating equations were employed to assess the association between body fat percentage and sperm count, motility, and morphology. We estimated that each 10% increase in total body fat percentage (estimated change [95% confidence interval, 95% CI]) was significantly associated with a 0.18 × 10 6 (0.09 × 10 6 -0.27 × 10 6 ) ml and 12.21 × 10 6 (4.52 × 10 6 -19.91 × 10 6 ) reduction in semen volume and total sperm count, respectively. Categorical analyses and exposure-response curves showed that the association of body fat distribution with semen volume and total sperm count was stronger at higher body fat percentages. In addition, the association still held among normal weight and overweight participants. We observed similar associations for upper limb, trunk, and lower limb body fact distributions. In conclusion, we found that a higher body fat distribution was significantly associated with lower semen quality (especially semen volume) even in men with a normal weight. These findings provide useful clues in exploring body fat as a risk factor for semen quality decline and add to evidence for improving semen quality for those who are expected to conceive.
Humans ; Male ; Adult ; Semen Analysis ; China ; Body Fat Distribution ; Longitudinal Studies ; Sperm Count ; Sperm Motility ; Body Mass Index ; Tissue Donors ; Obesity/complications* ; Spermatozoa ; Young Adult ; Middle Aged ; East Asian People

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

ObjectiveTo investigate the effect of liquiritigenin （LG） on intestinal flora in menopausal APP/PS1 mice. MethodsA total of forty 3-month-old female APP/PS1 mice were randomly divided into sham surgery group （n=20） and ovariectomy group （n=20）. Seven days after surgery， the ovariectomy group was randomly divided into ovariectomy control group （OVX， n=10）， ovariectomy + liquiritigenin treatment group （OVX + LG， n=10）， and the sham surgery group was randomly divided into liquiritigenin treatment group （LG， n=10） and reagent control group （Sham， n=10）， and ten C57BL/6J mice were taken as WT group. The dose of LG group and OVX + LG group was 30 mg•kg^-1•d^-1. After 90 days of drug treatment， fecal samples were gathered， genomes were extracted， and intestinal flora were analyzed by 16S rDNA Amplicon Sequencing. Morris water maze was performed to evaluate learning and memory abilities of mice. Immunofluorescence was used to observe the deposition of senile plaques （SP） in the brain of mice. ResultsThe results of water maze showed that LG significantly improved the learning memory ability of APP/PS1 mice with/without OVX （P<0.05）， and reduced the number of SPs in the brain of APP/PS1 mice with/without OVX， and the differences were statistically significant （P<0.000 1）. 16s rDNA sequencing analysis of the relative abundance of gut microbiota proved that LG treatment significantly increased the relative abundance of Firmicutes and Lactobacillus （P<0.05） and reduced the relative abundance of harmful bacteria belong to Bacteroidetes （P<0.05） in APP/PS1 mice intestines with/without menopause. After LG treatment， the relative abundance of Allobaculun elevated in the intestines of APP/PS1 mice， while declined in the intestines of menopausal APP/PS1 mice， but the difference was not statistically significant. LEfSe analysis revealed the bacteria with the most differential abundance of the gut microbiota of WT mice were Firmicutes， Bacillus， and Lactobacillales （P<0.05）； Lactobacillus reuteri had a greater influence on the LG group （P<0.05）； Bacteroidia， Bacteroidales and Bacteroides gathered in the intestines of mice in the Sham group （P<0.05）. Firmicutes and Allobaculum were the dominant in the WT group （P<0.05）； Bacteroides， Bacteroidia and Bacteroidales were more abundant in the Sham group（P<0.05）； Bacterroidaceae and Bacteroides had the most differential abundances in the OVX group （P<0.05）； Lactobacillaceae and Lactobacillus were more abundant in the intestines in the OVX + LG group （P<0.05）. ConclusionLG could improve the ratio of beneficial and harmful bacteria in the intestines of APP/PS1 mice before and after menopause. Liquiritigenin treatment showed consistent variations in intestinal flora in APP/PS1 mice with or without ovariectomy. It is presumed that menopausal APP/PS1 mice have lipid metabolism disorders which requires further study.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Puerarin was conjugated with bovine serum albumin(BSA) and ovalbumin(OVA) by periodate oxidation to serve as the immunogen and coating antigen, respectively. BALB/c mice were immunized with puerarin-BSA according to the routine immunization procedure, and the titer and specificity of serum were detected after three immunization. After booster immunization, mouse spleen lymphocytes were fused with mouse myeloma cells, and 24 hybridoma cell lines of the monoclonal antibodies against puerarin were screened by monoclonal antibody screening technique. Ascites was prepared and purified. The cross-reactivity of monoclonal antibody(mAb) M1 with 4'-methoxy puerarin, daidzin, puerarin-6″-O-xyloside, daidzein, mirificin, 3'-methoxy puerarin, and 3'-hydroxy puerarin was 239.84%, 112.18%, 67.89%, 58.28%, 22.37%, 0.40%, and 0.20%, respectively, and those with other analogs such as baicalein and baicalin were all less than 0.10%. The IC_(50) and the working range of the indirect competitive enzyme-linked immunosorbent assay(icELISA) for puerarin were 44.80 ng·mL~(-1) and 8.20-292.30 ng·mL~(-1), respectively. The average recovery was 91.95%-98.20% with an RSD in the range of 0.70%-2.60%. The content of puerarin in different Puerariae Lobatae Radix samples was determined with icELISA and validated by UPLC-MS. The correlation between data obtained from icELISA and UPLC-MS was 0.999 0, indicating that icELISA is suitable for the rapid detection of puerarin in Puerariae Lobatae Radix samples.
Animals ; Antibodies, Monoclonal ; Chromatography, Liquid ; Enzyme-Linked Immunosorbent Assay/methods* ; Hybridomas/metabolism* ; Isoflavones ; Mice ; Mice, Inbred BALB C ; Tandem Mass Spectrometry

OBJECTIVE: Through showing the full picture of double-arm controlled clinical research and systematic review evidence in the field of orally administrated Chinese herbal medicine (CHM) for treatment of lung cancer, to provide a reference for future clinical research and to indicate a direction for future systematic reviews. METHODS: A comprehensive search of clinical controlled studies was performed regarding orally administered CHM treatment for lung cancer published from January 1970 to September 2020. The language was restricted to Chinese and English. Relevant data were extracted, the quality of systematic reviews was evaluated, and the research evidence was visually displayed. RESULTS: Randomized controlled trials were the most common type of research design. The research sample sizes were typically small. Oral CHM showed certain curative advantages in treating lung cancer. The key stages in oral CHM intervention for lung cancer are chemotherapy, radiotherapy, and late palliative treatment. The advantageous outcomes of oral CHM treatment of lung cancer are the short-term efficacy, quality of life, and adverse reactions. The perioperative stage, overall survival, pharmacoeconomic evaluation, and Chinese medicine decoctions are weak research areas. CONCLUSIONS CHM has staged and therapeutic advantages in treating lung cancer. The overall methodological quality is poor, and the level of evidence requires improvement. It is necessary to carry out large-scale, standardized, and higher-quality research in the superior and weak areas of CHM treatment of lung cancer.
Drugs, Chinese Herbal/adverse effects* ; Humans ; Lung Neoplasms/drug therapy* ; Quality of Life ; Randomized Controlled Trials as Topic ; Systematic Reviews as Topic

ObjectiveThe law of fertilizer requirement serves as the basis for the fertilization of medicinal plants， development of special fertilizer， and high-quality medicinal materials. MethodThis study aims to explore the optimal potassium application rate for Panax ginseng to achieve high yield and quality of the medicinal material and targeted management of potassium fertilizer. To be specific， 6 concentration gradients （0， 2， 4， 8， 10， and 12 mmol·L^-1） of potassium sulfate （potassium fertilizer） were designed and applied to the 4-year-old P. ginseng in CK， C1， C2， C3， C4， and C5 treatments， respectively. Thereby， the influence of potassium concentration on P. ginseng was observed. ResultWhen potassium sulfate was applied at 8 mmol·L^-1， P. ginseng had the chlorophyll content of 32.13%， net photosynthetic rate of 2.548 8 µmol·m^-2·s^-1， and activities of superoxide dismutase （SOD）， peroxidase （POD）， and catalase （CAT） significantly higher than those in the CK， C1， C4， and C5 treatments （P<0.05）. The average fresh weight of P. ginseng roots was 6.25 g， 134% up from the CK， and the content of ginsenoside Rg₁ （5.24 mg·g^-1） and Re （4.17 mg·g^-1） and total saponins （12.33 mg·g^-1） was significantly higher than that in CK and other treatments （P<0.05）. Thus， 8 mmol·L^-1 potassium sulfate was most favorable for the growth and effective component accumulation of four-year-old P. ginseng. ConclusionThis study expounds the effect of potassium fertilizer on the yield and quality of P. ginseng， which is expected to help guide the precise application of potassium fertilizer in P. ginseng production in the field and lay a theoretical basis for the development of special fertilizer for P. ginseng and the optimization of fertilization technology.

Hyperglycemia is the dominant phenotype of diabetes and the main contributor of diabetic complications. Puerarin is widely used in cardiovascular diseases and diabetic vascular complications. However, little is known about its direct effects on diabetes. The aim of our study is to investigate its antidiabetic effect in vivo and in vitro, and explore the underlying mechanism. We used type I diabetic mice induced by streptozotocin to observe the effects of puerarin on glucose metabolism. In addition, oxidative stress and hepatic mitochondrial respiratory activity were evaluated in type I diabetic mice. In vitro, glucose consumption in HepG2 cells was assayed along with the qPCR detection of glucogenesis genes expression. Moreover, ATP production was examined and phosphorylation of AMPK was determined using Western blot. Finally, the molecular docking was performed to predict the potential interaction of puerarin with AMPK utilizing program LibDock of Discovery Studio 2018 software. The results showed that puerarin improved HepG2 glucose consumption and upregulated the glucogenesis related genes expression. Also, puerarin lowered fasting and fed blood glucose with improvement of glucose tolerance in type I diabetic mice. Further mechanism investigation showed that puerarin suppressed oxidative stress and improved hepatic mitochondrial respiratory function with enhancing ATP production and activating phosphorylation of AMPK. Docking study showed that puerarin interacted with AMPK activate site and enhancing phosphorylation. Taken together, these findings indicated that puerarin exhibited the hypoglycemic effect through attenuating oxidative stress and improving mitochondrial function via AMPK regulation, which may serve as a potential therapeutic option for diabetes treatment.

Erigeron breviscapus, a species within the genus of Erigeron, is mainly distributed in Southwest China. It is cold in property, slightly bitter in taste, and has the effect of dispersing cold table, removing wind and dehumidification, promoting blood circulation and removing blood stasis, relieving pain and inflammation. Breviscapine is the extract of E. breviscapus. It is mainly consisted of flavonoids, lignans, coumarins, terpenes, phytosterols, etc. As the major components of breviscapine, the content of breviscapine b (4′-hydroxybaicalin-7-O-glucuronide) and breviscapine a (apigenin-7-O-glucuronide) is greater than 90%. Modern pharmacological studies have shown that breviscapine has a wide range of pharmacological effects, including anti-oxidation, anti-fibrosis, anti-inflammation, anti-aging, anti-platelet aggregation, lowering blood lipid, increasing blood flow, improving microcirculation, preventing and treating tumors, and resisting brain injury. In clinical, breviscapine has been widely used in the treatment of diabetes, cerebral insufficiency, sequelae caused by cerebral hemorrhage, hypermucolipemia, cerebral thrombosis, kidney disease, liver disease, Alzheimer's disease, and some other complex diseases. Specially, in the treatment of diabetes and its chronic complications, such as diabetic nephropathy, diabetic cardiomyopathy, diabetic foot, diabetic retinopathy, breviscapine has showed significant efficacy. In addition, studies have demonstrated that the combined application of breviscapine, mecobalamine, and micopol can improve the therapeutic effect. In this work, the application of breviscapine in the treatment of chronic complications of diabetes mellitus and its related combination drugs were reviewed, by which we attempted to provide some valuable clues for the clinical application of breviscapine in the treatment of diabetes mellitus and its chronic complications.