Cinnamaldehyde: An effective component of Cinnamomum cassia inhibiting Helicobacter pylori.

ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum cassia Presl (Cinnamomum cassia) is a common traditional Chinese medicine, which can promote the secretion and digestion of gastric juice, improve the function of gastrointestinal tract. Cinnamaldehyde (CA) is a synthetic food flavoring in the Chinese Pharmacopoeia. AIM OF THE STUDY: This study aimed to search for the active ingredient (CA) of inhibiting H. pylori from Cinnamomum cassia, and elucidate mechanism of action, so as to provide the experimental basis for the treatment of H. pylori infection with Cinnamomum cassia. MATERIALS AND METHODS: It's in vitro and in vivo pharmacological properties were evaluated based on minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and an acute gastric inflammation model in mice infected with H. pylori. Drug safety was evaluated using the CCK8 method and high-dose administration in mice. The advantageous characteristics of CA in inhibiting H. pylori were confirmed using acidic conditions and in combination with the antibiotics. The mechanism underlying the action of CA on H. pylori was explored using scanning electron microscopy (SEM), adhesion experiments, biofilm inhibition tests, ATP and ROS release experiments, and drug affinity responsive target stability (DARTS) screening of target proteins. The protein function and target genes were verified by molecular docking and Real-Time quantitative reverse transcription PCR (qRT-PCR). RESULTS: The results demonstrated that CA was found to be the main active ingredient against H. pylori in Cinnamomum cassia in-vitro tests, with a MIC of 8-16 µg/mL. Moreover, CA effectively inhibited both sensitive and resistant H. pylori strains. The dual therapy of PPI + CA exhibited remarkable in vivo efficacy in the acute gastritis mouse model, superior to the standard triple therapy. DARTS, molecular docking, and qRT-PCR results suggested that the target sites of action were closely associated with GyrA, GyrB, AtpA, and TopA, which made DNA replication and transcription impossible, then leading to inhibition of bacterial adhesion and colonization, suppression of biofilm formation, and inhibition ATP and enhancing ROS. CONCLUSIONS: This study demonstrated the suitability of CA as a promising lead drug against H. pylori, The main mechanisms can target GyrA ect, leading to reduce ATP and produce ROS, which induces the apoptosis of bacterial.

[Quality evaluation of salt-fired Eucommiae Cortex based on HPLC fingerprint, multi-component content determination, and chemometrics].

This study established an HPLC fingerprint and multi-component content determination method for salt-fired Eucommiae Cortex, and evaluated the quality of salt-fired Eucommiae Cortex from different sources using fingerprint similarity evaluation, cluster analysis(CA), principal component analysis(PCA), and orthogonal partial least square discriminate analysis(OPLS-DA). HPLC was launched on a Cosmosil 5C_(18)-MS-Ⅱ column(4.6 mm×250 mm, 5 µm) by gradient elution with a mobile phase of methanol-0.2% phosphoric acid aqueous solution at a flow rate of 1.0 mL·min~(-1), detection wavelength of 238 nm, column temperature of 30 ℃, and an injection volume of 10 µL. The results of fingerprint similarity evaluation for 20 batches of salt-fired Eucommiae Cortex indicated that, except for batch S3 with a similarity of 0.893, the similarity of the other 19 batches was of ≥ 0.919, suggesting good similarity. Fourteen common peaks were calibrated and seven common peaks were identified including geniposidic acid. The mass fractions of geniposidic acid, chlorogenic acid, geniposide, genipin, pinoresinol diglucoside, liriodendrin, and pinoresinol-4-O-ß-D-glucopyranoside were 0.062 0%-0.426 9%, 0.024 9%-0.116 5%, 0.009 5%-0.052 9%, 0.005 5%-0.034 8%, 0.115 9%-0.317 8%, 0.016 4%-0.108 8%, and 0.026 4%-0.039 8%, respectively. Using CA, PCA, and OPLS-DA, the 20 batches of salt-fired Eucommiae Cortex were classified into three categories. Additionally, through the analysis of variable importance in projection(VIP) under OPLS-DA, two differential quality markers, geniposidic acid and chlorogenic acid, were identified. The established HPLC fingerprint and multi-component content determination method is stable and reliable, providing a reference for quality control of salt-fired Eucommiae Cortex.

Effects of dietary astaxanthin on growth performance, muscle composition, non-specific immunity, gene expression, and ammonia resistance of juvenile ivory shell (Babylonia areolate).

Astaxanthin is one of the important immunopotentators in aquaculture. However, little is known about the physiological changes and stress resistance effects of astaxanthin in marine gastropods. In this study, the effects of different astaxanthin concentrations (0, 25, 50, 75, and 100 mg/kg) on the growth, muscle composition, immune function, and resistance to ammonia stress in Babylonia areolata were investigated after three months of rearing. With the increase in astaxanthin content, the weight gain rate (WGR), specific growth rate (SGR), and survival rate (SR) of B. areolata showed an increasing trend. The 75-100 mg/kg group was significantly higher than the control group (0 mg/kg). There was no significant difference in the flesh shell ratio (FSR), viscerosomatic index (VSI), and soft tissue index (STI) of the experimental groups. Astaxanthin (75 mg/kg) significantly increased muscle crude protein content and increased hepatopancreas alkaline phosphatase (AKP), superoxide dismutase (SOD), and catalase (CAT) activity. Astaxanthin (75-100 mg/kg) significantly increased the total antioxidant capacity (T-AOC) and acid phosphatase (ACP) of the hepatopancreas and decreased the malondialdehyde (MDA) content of B. areolata. Astaxanthin significantly induced the expression levels of functional genes, such as SOD, Cu/ZnSOD, ferritin, ACP, and CYC in hepatopancreas and increased the survival rate of B. areolata under ammonia stress. The addition of 75-100 mg/kg astaxanthin to the feed improved the growth performance, muscle composition, immune function, and resistance to ammonia stress of B. areolata.

Effects of dietary chitosan oligosaccharide on the growth, intestinal microbiota and immunity of juvenile red claw crayfish (Cherax quadricarinatus).

This study aimed to evaluate the potential benefits of chitosan oligosaccharide (COS) on red claw crayfish (Cherax quadricarinatus) and explore its underlying mechanisms. The crayfish were randomly divided into six groups, and the diets were supplemented with COS at levels of 0 (C0), 0.2 (C1), 0.4 (C2), 0.6 (C3), 0.8 (C4), and 1 (C5) g kg-1. Treatment with COS significantly improved the growth performance of the crayfish with a higher weight gain rate (WGR) and specific growth rate (SGR) in the C2 group compared to the C0 group. Additionally, the content of crude protein in the crayfish muscles in the C1 group was significantly higher than that of the C0 group. Regarding non-specific immunity, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and alkaline phosphatase (AKP), and the levels of expression of the genes related to immunity (SOD; anti-lipopolysaccharide factor [ALF]; thioredoxin1 [Trx1]; C-type lysozyme, [C-LZM]; and GSH-Px) in the hepatopancreas and hemolymph increased significantly (P < 0.05) after supplementation with 0.4 g kg-1 of COS, while the content of malondialdehyde (MDA) decreased (P < 0.05). The survival rate of C. quadricarinatus increased (P < 0.05) in the C2, C3, C4, and C5 groups after the challenge with Aeromonas hydrophila. This study found that COS has the potential to modulate the composition of the intestinal microbiota and significantly reduce the abundance of species of the phylum Proteobacteria and the genera Aeromonas and Vibrio in the gut of C. quadricarinatus, while the abundance of bacteria in the phylum Firmicutes and the genus Candidatus_Hepatoplasma improved significantly. This study suggests that the inclusion of COS in the diet of C. quadricarinatus can enhance growth, boost immunity, and increase resistance to infection with A. hydrophila, especially when supplemented at 0.4-0.8 g kg-1.

The role of autophagy in the treatment of type II diabetes and its complications: a review.

Type II diabetes mellitus (T2DM) is a chronic metabolic disease characterized by prolonged hyperglycemia and insulin resistance (IR). Its incidence is increasing annually, posing a significant threat to human life and health. Consequently, there is an urgent requirement to discover effective drugs and investigate the pathogenesis of T2DM. Autophagy plays a crucial role in maintaining normal islet structure. However, in a state of high glucose, autophagy is inhibited, resulting in impaired islet function, insulin resistance, and complications. Studies have shown that modulating autophagy through activation or inhibition can have a positive impact on the treatment of T2DM and its complications. However, it is important to note that the specific regulatory mechanisms vary depending on the target organ. This review explores the role of autophagy in the pathogenesis of T2DM, taking into account both genetic and external factors. It also provides a summary of reported chemical drugs and traditional Chinese medicine that target the autophagic pathway for the treatment of T2DM and its complications.

Sources, morphology, phytochemistry, pharmacology of Curcumae Longae Rhizoma, Curcumae Radix, and Curcumae Rhizoma: a review of the literature.

Curcumae Longae Rhizoma (turmeric), Curcumae Radix and Curcumae Rhizoma are derived from the Curcuma species, and have gradually become three of the most commonly used medicinal herbs in China due to their different origins, processing methods and medicinal part. These three herbs have certain similarities in morphology, chemical composition, and pharmacological effects. All three of these herbs contain curcuminoids and volatile oil compounds, which exhibit anti-inflammatory, anti-tumor, antioxidant, and neuroprotective properties, although modern clinical applications have their own requirements. At present, there is no systematic guidelines for the clinical application of these three of Curcuma species; consequently, there is a high risk of unwanted phenomena associated with the mixing and indiscriminate use of these herbs. In this review, we focus predominantly on morphology, chemical composition, and the pharmacological activity of these three Curcuma herbs and summarize the current status of research in this field. Our goal is to provide a better understanding of clinical value of these Curcuma species so that we can provide reference guidelines for their further development, utilization and rational clinical application.

New cyclic C-geranylflavanones isolated from Paulownia fortunei fruits with their anti-proliferative effects on three cancer cell lines.

Seven new C-geranylated flavanones, fortunones F - L (1-7), were isolated from the fresh mature fruits of Paulownia fortunei (Seem.) Hemsl. Their structures were determined by extensive spectroscopic data interpretation (UV, IR, HRMS, NMR, and CD). These new isolated compounds were all with a cyclic side chain modified from the geranyl group. Among them, compounds 1-3 all possessed a dicyclic geranyl modification, which was described firstly for Paulownia C-geranylated flavonoids. All the isolated compounds were subjected to the cytotoxic assay on human lung cancer cell A549, mouse prostate cancer cell RM1 and human bladder cancer cell T24, respectively. Results indicated A549 cell line was more sensitive to C-geranylated flavanones than the other two cancer cell lines and compounds 1, 7 and 8 exhibited potential anti-tumor effects (IC50 ˂ 10 µM). Further research revealed the effective C-geranylated flavanones could exert their anti-proliferative activity on A549 cells by inducing apoptosis and blocking cells in G1 phase.

Babao Dan decreases hepatocarcinogenesis by inhibiting hepatic progenitor cells malignant transformation via down-regulating toll-like receptor 4.

Background: Babao Dan (BBD) is a traditional Chinese medicine that has been widely used as a complementary and alternative medicine to treat chronic liver diseases. In this study, we aimed to observe the effect of BBD on the incidence of diethylnitrosamine (DEN)-initiated hepatocellular carcinoma formation in rats and explored its possible mechanism. Methods: To verify this hypothesis, BBD was administrated to rats at a dose of 0.5g/kg body weight per two days from the 9th to 12th week in HCC-induced by DEN. Liver injury biomarkers and hepatic inflammatory parameters were evaluated by histopathology as well as serum and hepatic content analysis. We applied immunohistochemical analysis to investigate the expression of CK-19 and SOX-9 in liver tissues. The expression of TLR4 was determined by immunohistochemical, RT-PCR, and western blot analysis. Furthermore, we also detected the efficacy of BBD against primary HPCs neoplastic transformation induced by LPS. Results: We observed that DEN could induce hepatocarcinogenesis, and BBD could obviously decrease the incidence. The biochemical and histopathological examination results confirmed that BBD could protect against liver injury and decrease inflammatory infiltration. Immunohistochemistry staining results showed that BBD could effectively inhibit the ductal reaction and the expression of TLR4. The results showed that BBD-serumcould obviously inhibit primary HPCs neoplastic transformation induced by regulating the TLR4/Ras/ERK signaling pathway. Conclusion: In summary, our results indicate that BBD has potential applications in the prevention and treatment of HCC, which may be related to its effect on hepatic progenitor cells malignant transformation via inhibiting the TLR4/Ras/ERK signaling pathway.

Efficacy and safety of salvianolate and enoxaparin in the prevention of perioperative deep venous thrombosis in gastrointestinal surgery.

OBJECTIVE: In this study, the efficacy and safety of salvianolate were compared with enoxaparin in the prevention of perioperative deep vein thrombosis in gastrointestinal surgery. METHODS: From October 2017 to September 2019, 563 patients who underwent gastrointestinal surgery were collected. Based on the inclusion and exclusion criteria, 119 patients were divided into two groups: enoxaparin group (n = 65) and salvianolate group (n = 54). Comparisons were made regarding the outcomes: prothrombin time (PT), prothrombin activity (PTA), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), D-dimer level (D-D), platelet count (PLT), hematokrit (HCT), and incidence of deep vein thrombosis (DVT). RESULTS: The main outcomes showed no significance between enoxaparin group and salvianolate group (p > .05). The incidence of DVT in salvianolate group was 1.85%, significantly lower than that in enoxaparin group (12.3%) (p < .05). No serious adverse reactions occurred in the two groups during treatment. CONCLUSION: Compared with enoxaparin, salvianolate has an advantage in the prevention of perioperative thrombosis in gastrointestinal surgery with a lower incidence of DVT.

Effects of hepatitis B virus infection and strategies for preventing mother-to-child transmission on maternal and fetal T-cell immunity.

One of the most common routes of chronic hepatitis B virus (HBV) infection is mother-to-child transmission (MTCT). Approximately 6.4 million children under the age of five have chronic HBV infections worldwide. HBV DNA high level, HBeAg positivity, placental barrier failure, and immaturity of the fetal immune are the possible causes of chronic HBV infection. The passive-active immune program for children, which consists of the hepatitis B vaccine and hepatitis B immunoglobulin, and antiviral therapy for pregnant women who have a high HBV DNA load (greater than 2 × 105 IU/ml), are currently two of the most important ways to prevent the transmission of HBV from mother to child. Unfortunately, some infants still have chronic HBV infections. Some studies have also found that some supplementation during pregnancy can increase cytokine levels and then affect the level of HBsAb in infants. For example, IL-4 can mediate the beneficial effect on infants' HBsAb levels when maternal folic acid supplementation. In addition, new research has indicated that HBV infection in the mother may also be linked to unfavorable outcomes such as gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, and premature rupture of membranes. The changes in the immune environment during pregnancy and the hepatotropic nature of HBV may be the main reasons for the adverse maternal outcomes. It is interesting to note that after delivery, the women who had a chronic HBV infection may spontaneously achieve HBeAg seroconversion and HBsAg seroclearance. The maternal and fetal T-cell immunity in HBV infection is important because adaptive immune responses, especially virus-specific CD8 T-cell responses, are largely responsible for viral clearance and disease pathogenesis during HBV infection. Meanwhile, HBV humoral and T-cell responses are important for the durability of protection after fetal vaccination. This article reviews the literature on immunological characteristics of chronic HBV-infected patients during pregnancy and postpartum, blocking mother-to-child transmissions and related immune mechanisms, hoping to provide new insights for the prevention of HBV MTCT and antiviral intervention during pregnancy and postpartum.

Coexposure to multiple metals and renal tubular damage: a population-based cross-sectional study in China's rural regions.

Previous studies have indicated that exposure to a single toxic metal can cause renal tubular damage, while evidence about the effects of multimetal exposure on renal tubular damage is relatively limited. We aimed to evaluate the relationships of multimetal coexposure with renal tubular damage in adults in heavy metal-polluted rural regions of China. A cross-sectional study of 1918 adults in China's heavy metal-contaminated rural regions was conducted. Inductively coupled plasma-mass spectrometry (ICP-MS) was used to measure the plasma levels of 18 metals in participants, and immune turbidimetry was used to measure sensitive biological indicators, reflecting renal tubular damage (including retinol-binding protein and ß2-microglobulin). Least absolute shrinkage and selection operator (LASSO) penalized regression analysis, logistic and linear regression analysis, restricted cubic spline (RCS) regression analysis and the Bayesian kernel machine regression (BKMR) method were used to explore associations of multimetal coexposure with renal tubular damage risk or renal tubular damage indicators. Plasma selenium, cadmium, arsenic, and iron were identified as the main plasma metals associated with renal tubular damage risk after dimensionality reduction. Multimetal regression models showed that selenium was positively associated, and iron was negatively associated with renal tubular damage risk or its biological indicators. Multimetal RCS analyses additionally revealed a non-linear relationship of selenium with renal tubular damage risk. The BKMR models showed that the metal mixtures were positively associated with biological indicators of renal tubular damage when the metal mixtures were above the 50th percentile of concentration. Our findings indicated that natural exposure to high levels of multimetal mixtures increases the risk of renal tubular damage. Under the conditions of multimetal exposure, selenium was positively associated, and iron was negatively associated with renal tubular damage risk or its biological indicators.

Efficacy and Safety of Glycyrrhizic Acid in Treatment of Autoimmune Hepatitis.

To compare the long-term efficacy and safety of glycyrrhizic acid preparation and hormone treatment in patients with autoimmune hepatitis, we enrolled 377 patients in a study that lasted from January 2009 to January 2020. After performing propensity score matching, we included 58 patients in the hormone group and 58 in the glycyrrhizic acid preparation group in statistical analysis. We then compared the ratio of sustained biochemical responses at 48 weeks after treatment. Adverse events, including some incidence of decompensated liver cirrhosis and liver cancer, were evaluated. The results showed that a total of 61.8% of treated patients achieved complete biochemical remission. The cumulative biochemical remission rate in the hormone group and glycyrrhizic acid preparation group showed no significant difference (62.3% vs. 60.7%, [Formula: see text], [Formula: see text]). At the end of follow-up, the total bile acid in the hormone group was significantly higher than that in the glycyrrhizic acid preparation group (8.9[Formula: see text][Formula: see text]mol/L vs. 5.6[Formula: see text][Formula: see text]mol/L, [Formula: see text], [Formula: see text]). The incidence of adverse reactions in the hormone group was significantly higher than that in the glycyrrhizic acid preparation group (31.03% vs. 15.52%, [Formula: see text], [Formula: see text]). In conclusion, compared with the hormone treatment, glycyrrhizic acid preparation might be a safe and effective treatment for autoimmune hepatitis.

Treatment of tibial large bone defects: A comparative study of bone transport over an intramedullary nail in combination with antibiotic-impregnated calcium sulphate versus bone transport alone with antibiotic-impregnated calcium sulphate.

PURPOSE: To compare the bone transport over an intramedullary nail in combination with antibiotic-impregnated calcium sulphate versus bone transport alone with antibiotic-impregnated calcium sulphate for the treatment of tibial large bone defects. METHODS: A retrospective analysis was conducted by enroling 33 surgically treated patients with tibial large bone defects after the debridement for tibial infection or osteomyelitis who were admitted in Lower Limb Surgery Ward of Traumatic orthopaedic Department, Xi'an Honghui Hospital from January 2018 to January 2021. All the patients were categorized in Group A (transport over intramedullary nail, 12 cases) and Group B (transport alone, 21 cases) based on the surgery strategy. The collected clinical materials and data included gender, age, injury mechanism, smoking habits, comorbidity diseases, initial fracture type (open or close), bone defect size, surgical duration, intraoperative bleeding loss, resorption time of calcium sulphate, bone transport time, external fixation time, external fixation index, weight bearing time, complications and Paley bone and functional criteria. RESULTS: Thirty-three patients were enroled and successfully followed up with an average time of 15.25±4.31 months ranged from 8 to 21 months in Group A and an average time of 17.09±5.64 months ranged from 9 to 31 months in Group B. No significantly statistical differences of the demographic data were discovered between the two groups. There were no significantly statistical differences of the average bone defect size, intraoperative bleeding loss, resorption time of calcium sulphate and bone transport time between the two groups. However, the average surgical duration (P = 0.002) was significantly longer in Group A than Group B and the average external fixation time (P<0.001), external fixation index(P = 0.002) and weight bearing time (P = 0.030) were significantly shorter in Group A than Group B. No significantly statistical difference of excellent and good rate of bone outcomes and complication rate was observed, however, the excellent and good rate of functional outcomes (P = 0.041) was significantly higher in Group A than Group B. CONCLUSION: Compared with the conventional Ilizarov technique combining with antibiotic-impregnated calcium sulphate for large tibial bone defects, bone transport over an intramedullary nail in combination with antibiotic-impregnated calcium sulphate had favourable external fixation time, external fixation index, weight bearing time and clinical functional outcomes which effectively suppressed the infection and allowed patients earlier removal of the external fixator and weight bearing for rehabilitation.

Fexaramine improves non-alcoholic fatty liver disease in mice by stimulating intestinal FXR / 药学学报

Non-alcoholic fatty liver disease (NAFLD) is considered to be a manifestation of metabolic syndrome and has become one of the chronic diseases that endanger health around the world. There is still a lack of effective therapeutic drugs in clinical practice. Farnesoid X receptor (FXR) has been a popular target for NAFLD research in recent years. Fexaramine (Fex) is a potent and selective agonist of FXR, and its mechanism of action to improve NAFLD is unclear. Therefore, in this study, a mouse model of NAFLD was constructed using a high-fat, high-cholesterol diet and treated with Fex orally for 6 weeks. We evaluated the ameliorative effect of Fex on disorders of glucolipid metabolism in NAFLD mice, and preliminarily explored its potential mechanism of action. The animal experiments were approved by the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval number: PZSHUTCM210913011). In this study, it was found that 100 mg·kg-1 Fex significantly inhibited body weight gain, alleviated insulin resistance, improved liver injury and lipid accumulation in NAFLD mice. The effect of Fex on the expression of hepatic intestinal FXR and its target genes in NAFLD mice was further examined. Analysis of serum and hepatic bile acid profiles and expression related to hepatic lipid metabolism. It was found that Fex could stimulate intestinal FXR, promote fibroblast growth factor 15 (FGF15) secretion, inhibit the expression of cytochrome P450 family 7 subfamily A member 1 (CYP7A1), the rate-limiting enzyme of bile acid synthesis in liver, regulate bile acid synthesis by negative feedback, and improve the disorder of bile acid metabolism. At the same time, Fex reduces liver lipid synthesis and absorption, increases fatty acid oxidation, thus improving liver lipid metabolism. This study shows that Fex can improve NAFLD by activating intestinal FXR-FGF15 signal pathway and regulating liver lipid metabolism.

Study on HBV-related acute-on-chronic liver failure risk factors and novel predictive survival model / 中华肝脏病杂志

Objective: To identify the predisposing factors, clinical characteristics, and risk factors of disease progression to establish a novel predictive survival model and evaluate its application value for hepatitis B virus-related acute-on-chronic liver failure. Methods: 153 cases of HBV-ACLF were selected according to the guidelines for the diagnosis and treatment of liver failure (2018 edition) of the Chinese Medical Association Hepatology Branch. Predisposing factors, the basic liver disease stage, therapeutic drugs, clinical characteristics, and factors affecting survival status were analyzed. Cox proportional hazards regression analysis was used to screen prognostic factors and establish a novel predictive survival model. The receiver operating characteristic curve (ROC) was used to evaluate predictive value with the Model for End-Stage Liver Disease (MELD) and the Chronic Liver Failure Consortium Acute-on-Chronic Liver Failure score (CLIF-C ACLF). Results: 80.39% (123/153) based on hepatitis B cirrhosis had developed ACLF. HBV-ACLF's main inducing factors were the discontinuation of nucleos(t)ide analogues (NAs) and the application of hepatotoxic drugs, including Chinese patent medicine/Chinese herbal medicine, non-steroidal anti-inflammatory drugs, anti-tuberculosis drugs, central nervous system drugs, anti-tumor drugs, etc. 34.64% of cases had an unknown inducement. The most common clinical symptoms at onset were progressive jaundice, poor appetite, and fatigue. The short-term mortality rate was significantly higher in patients complicated with hepatic encephalopathy, upper gastrointestinal hemorrhage, hepatorenal syndrome, and infection (P < 0.05). Lactate dehydrogenase, albumin, the international normalized ratio, the neutrophil-to-lymphocyte ratio, hepatic encephalopathy, and upper gastrointestinal bleeding were the independent predictors for the survival status of patients. The LAINeu model was established. The area under the curve for evaluating the survival of HBV-ACLF was 0.886, which was significantly higher than the MELD and CLIF-C ACLF scores (P < 0.05), and the prognosis was worse when the LAINeu score ≥ -3.75. Conclusion: Discontinuation of NAs and the application of hepatotoxic drugs are common predisposing factors for HBV-ACLF. Hepatic decompensation-related complications and infection accelerate the disease's progression. The LAINeu model can predict patient survival conditions more accurately.

Genomic Testing in Localized Prostate Cancer Can Identify Subsets of African Americans With Aggressive Disease.

BACKGROUND: Personalized genomic classifiers have transformed the management of prostate cancer (PCa) by identifying the most aggressive subsets of PCa. Nevertheless, the performance of genomic classifiers to risk classify African American men is thus far lacking in a prospective setting. METHODS: This is a prospective study of the Decipher genomic classifier for National Comprehensive Cancer Network low- and intermediate-risk PCa. Study-eligible non-African American men were matched to African American men. Diagnostic biopsy specimens were processed to estimate Decipher scores. Samples accrued in NCT02723734, a prospective study, were interrogated to determine the genomic risk of reclassification (GrR) between conventional clinical risk classifiers and the Decipher score. RESULTS: The final analysis included a clinically balanced cohort of 226 patients with complete genomic information (113 African American men and 113 non-African American men). A higher proportion of African American men with National Comprehensive Cancer Network-classified low-risk (18.2%) and favorable intermediate-risk (37.8%) PCa had a higher Decipher score than non-African American men. Self-identified African American men were twice more likely than non-African American men to experience GrR (relative risk [RR] = 2.23, 95% confidence interval [CI] = 1.02 to 4.90; P = .04). In an ancestry-determined race model, we consistently validated a higher risk of reclassification in African American men (RR = 5.26, 95% CI = 1.66 to 16.63; P = .004). Race-stratified analysis of GrR vs non-GrR tumors also revealed molecular differences in these tumor subtypes. CONCLUSIONS: Integration of genomic classifiers with clinically based risk classification can help identify the subset of African American men with localized PCa who harbor high genomic risk of early metastatic disease. It is vital to identify and appropriately risk stratify the subset of African American men with aggressive disease who may benefit from more targeted interventions.

Domestication of farmed fish via the attenuation of stress responses mediated by the hypothalamus-pituitary-inter-renal endocrine axis.

Human-directed domestication of terrestrial animals traditionally requires thousands of years for breeding. The most prominent behavioral features of domesticated animals include reduced aggression and enhanced tameness relative to their wild forebears, and such behaviors improve the social tolerance of domestic animals toward both humans and crowds of their own species. These behavioral responses are primarily mediated by the hypothalamic-pituitary-adrenal (inter-renal in fish) (HPA/I) endocrine axis, which is involved in the rapid conversion of neuronal-derived perceptual information into hormonal signals. Over recent decades, growing evidence implicating the attenuation of the HPA/I axis during the domestication of animals have been identified through comprehensive genomic analyses of the paleogenomic datasets of wild progenitors and their domestic congeners. Compared with that of terrestrial animals, domestication of most farmed fish species remains at early stages. The present review focuses on the application of HPI signaling attenuation to accelerate the domestication and genetic breeding of farmed fish. We anticipate that deeper understanding of HPI signaling and its implementation in the domestication of farmed fish will benefit genetic breeding to meet the global demands of the aquaculture industry.

Role of Traditional Chinese Medicine in Treating Severe or Critical COVID-19: A Systematic Review of Randomized Controlled Trials and Observational Studies.

Background: The coronavirus disease 2019 (COVID-19) continues to spread globally. Due to the higher risk of mortality, the treatment of severe or critical patients is a top priority. Traditional Chinese medicine (TCM) treatment has played an extremely important role in the fight against COVID-19 in China; a timely evidence summary on TCM in managing COVID-19 is crucial to update the knowledge of healthcare for better clinical management of COVID-19. This study aimed to assess the effects and safety of TCM treatments for severe/critical COVID-19 patients by systematically collecting and synthesizing evidence from randomized controlled trials (RCTs) and observational studies (e.g., cohort). Methods: We searched nine databases up to 19th March 2022 and the reference lists of relevant publications. Pairs of reviewers independently screened studies, extracted data of interest, and assessed risk of bias. We performed qualitative systematic analysis with visual presentation of results and compared the direction and distribution of effect estimates for each patient's important outcome. We performed sensitivity analyses to observe the robustness of results by restricting analysis to studies with low risk of bias. Results: The search yielded 217,761 records, and 21 studies (6 RCTs and 15 observational studies) proved eligible. A total of 21 studies enrolled 12,981 severe/critical COVID-19 patients with a mean age of 57.21 years and a mean proportion of men of 47.91%. Compared with usual supportive treatments, the effect estimates of TCM treatments were consistent in direction, illustrating that TCM treatments could reduce the risk of mortality, rate of conversion to critical cases, and mechanical ventilation, and showed significant advantages in shortening the length of hospital stay, time to viral clearance, and symptom resolution. The results were similar when we restricted analyses to low-risk-bias studies. No serious adverse events were reported with TCM treatments, and no significant differences were observed between groups. Conclusion: Encouraging evidence suggests that TCM presents substantial advantages in treating severe/critical COVID-19 patients. TCM has a safety profile that is comparable to that of conventional treatment alone. TCMs have played an important role in China's prevention and treatment of COVID-19, which sets an example of using traditional medicine in preventing and treating COVID-19 worldwide.

Baseline lymphocyte and cholinesterase levels may be the predictors of chronic herbal drug-induced liver injury.

Objective: To investigate the factors influencing the chronicity of drug-induced liver injury (DILI) caused by Chinese herbal medicine. Methods: Patients with DILI diagnosed by using the RUCAM score were enrolled retrospectively. The subjects were patients with DILI induced by taking Chinese herbal medicine and were followed up for 48 weeks. These patients were divided into a cure group and a chronic group. The biochemical indicators were monitored at baseline and every 3 months. Logistic regression was used to analyze the risk factors of DILI chronicity. The ROC (receiver operator characteristic) curve was used to analyze the diagnostic efficiency of each factor. Results: A total of 420 patients with DILI were enrolled; 122 of them were caused by Chinese herbal medicine, 70.5% (86/122) of them were female, chronic group 31.2% (39/122), and cure group 68.0% (83/122); cholinesterase (ChE) in the chronic group was lower than that in the cure group (5467.10 ± 2010.40 U/L vs. 6248.52 ± 1901.78 U/L, p = 0.04, t = 2.078). There was no significant difference in the age between cured patients and chronic patients (p = 0.156, Z = -1.417). There was no significant difference between the prognosis of different genders (p = 0.521, Z = -0.639). The logistic regression analysis showed that baseline lymphocyte (OR = 0.429, 95%CI = 0.205-0.898, p = 0.025) and cholinesterase (OR = 0.088, 95%CI = 0.008-0.994, p = 0.049) were independent risk factors of drug-induced chronicity. Conclusion: Baseline lymphocyte and cholinesterase may be the predictive factors for the chronicity of Chinese herbal medicine-induced liver injury.

Study of Correlation between Intestinal Microbiota and Traditional Chinese Medicine Syndrome of Patients with Colon Cancer.

Objective: This research aims to study the material basis of the formation and specific bacteria of traditional Chinese medicine (TCM) syndrome from the characteristics of the intestinal microbiota of patients with colon cancer (CC) before and after the operation. Methods: A cross-sectional study was conducted on 84 patients with CC and 24 healthy controls. A total of 168 and 24 stool samples were collected from CC patients before and after the operation and healthy controls. DNA was extracted from 192 stool samples and then amplified using PCR. The V3-V4 high variable areas were analyzed by 16s rDNA sequencing. Results: The community diversity, in descending order, was the healthy control group and postoperative and preoperative groups of CC patients. The abundance of beneficial bacteria was postoperative group of CC patients > healthy control group > preoperative group of CC patients. Among the comparisons of the intestinal microbiota of preoperative groups of CC patients with different TCM syndromes, the community diversity in descending order was damp heat accumulation (DHA), spleen deficiency and dampness (SDD), spleen and kidney yang deficiency (SKYD), liver and kidney yin deficiency (LKYD), and deficiency of qi and blood (QBD), respectively. Specific microbiome analysis showed that the differences in the abundance of 42 taxons were statistically significant among the preoperative groups of CC patients with the five TCM syndromes and the healthy control group. While comparing the intestinal microbiota of postoperative groups with the five TCM syndromes, the community diversity in descending order is DHA, SDD, LKYD, SKYD, and QBD. Specific microbiome analysis showed that the differences in the abundance of 46 taxons were statistically significant among the postoperative groups of CC patients with the five TCM syndromes and the healthy control group. Streptococcus and Streptococcus mutans showed no statistical significance between the preoperative group and postoperative groups of CC with DHA syndrome (P > 0.05). Bacteroides at phylum and genus levels showed that there was no statistical significance between the preoperative group and the postoperative group of CC with SKYD syndrome (P > 0.05). Conclusions: Before and after surgery, with the deterioration of TCM syndrome: DHA ⟶ SDD ⟶ SKYD ⟶ LKYD ⟶ QBD, the number of beneficial bacteria in CC patients' intestines decreased while the number of pathogenic bacteria increased, and the community structure of intestinal microbiota tends to be unitized, indicating a serious intestinal microbiological disorder. After radical surgery and perioperative intervention, the intestinal microbiota diversity and community structure of postoperative CC patients were closer to those of healthy people than preoperative. However, they were still imbalanced. The intestinal microbiota of CC patients with different TCM syndromes differs significantly, which is important for understanding the pathogenesis of CC in TCM. The DHA and SKYD syndromes in CC patients before and after surgery showed significant differences in the microbial structure. Streptococcus and Streptococcus mutans were the specific species with a significant difference in CC patients with DHA syndrome, while bacteroides were the specific species in CC patients with SKYD syndrome.