Environmental explanation of prostate cancer progression based on the comprehensive analysis of polychlorinated biphenyls.

OBJECTIVE: Polychlorinated biphenyls (PCBs) have caused great environmental concerns. The study aims to investigate underlying molecular mechanisms between PCBs exposure and prostate cancer (PCa). METHODS: To investigate the association between PCBs exposure and prostate cancer by using CTD, TCGA, and GEO datasets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore pathways associated with PCBs-related genes (PRGs). Using Lasso regression analysis, a novel PCBs-related prognostic model was developed. Both internal and external validations were conducted to assess the model's validity. Molecular docking was utilized to assess the binding capacity of PCBs to crucial genes. At last, preliminary experimental validations were conducted to confirm the biological roles of Aroclor 1254 in PCa cells. RESULTS: The GO enrichment analysis of PRGs revealed that the biological processes were most enriched in the regulation of transcription from the RNA polymerase II promoter and signal transduction. The KEGG enrichment analysis showed that of the pathways in cancer is the most significantly enriched. Next, a PCBs-related model was constructed. In the training, test, GSE70770, and GSE116918 cohorts, the biochemical recurrences free survival of the patients with high-risk scores was considerably lower. The AUCs at 5 years were 0.691, 0.718, 0.714, and 0.672 in the four cohorts, demonstrating the modest predictive ability. A nomogram that incorporated clinical characteristics was constructed. The results of the anti-cancer drug sensitivity analysis show chemotherapy might be more beneficial for patients at low risk. The molecular docking analysis demonstrated PCBs' ability to bind to crucial genes. PCa cells exposed to Aroclor 1254 at a concentration of 1 µM showed increased proliferation and invasion capabilities. CONCLUSIONS: This study provides new insights into the function of PCBs in PCa and accentuates the need for deeper exploration into the mechanistic links between PCBs exposure and PCa progression.

A Novel Classification System of Renal Hilar Tumors for Surgical Guidance: Technique, Outcome, and Safety.

BACKGROUND: This study was designed to develop an innovative classification and guidance system for renal hilar tumors and to assess the safety and effectiveness of robot-assisted partial nephrectomy (RAPN) for managing such tumors. METHODS: A total of 179 patients undergoing RAPN for renal hilar tumors were retrospectively reviewed. A novel classification system with surgical techniques was introduced and the perioperative features, tumor characteristics, and the efficacy and safety of RAPN were compared within subgroups. RESULTS: We classified the tumors according to our novel system as follows: 131 Type I, 35 Type II, and 13 Type III. However, Type III had higher median R.E.N.A.L., PADUA, and ROADS scores compared with the others (all p < 0.001), indicating increased operative complexity and higher estimated blood loss [180.00 (115.00-215.00) ml]. Operative outcomes revealed significant disparities between Type III and the others, with longer operative times [165.00 (145.00-200.50) min], warm ischemia times [24.00 (21.50-30.50) min], tumor resection times [13.00 (12.00-15.50) min], and incision closure times [22.00 (20.00-23.50) min] (all p < 0.005). Postoperative outcomes also showed significant differences, with longer durations of drain removal (77.08 ± 18.16 h) and hospitalization for Type III [5.00 (5.00-6.00) d] (all p < 0.05). Additionally, Type I had a larger tumor diameter than the others (p = 0.009) and pT stage differed significantly between the subtypes (p = 0.020). CONCLUSIONS: The novel renal hilar tumor classification system is capable of differentiating the surgical difficulty of RAPN and further offers personalized surgical steps tailored to each specific classification. It provides a meaningful tool for clinical practice.

Loss of NAT10 alleviates maternal high-fat diet-induced hepatic steatosis in male offspring of mice.

OBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming an escalating health problem in pediatric populations. This study aimed to investigate the role of N-acetyltransferase 10 (NAT10) in maternal high-fat diet (HFD)-induced MASLD in offspring at early life. METHODS: We generated male hepatocyte-specific NAT10 knockout (Nat10HKO) mice and mated them with female Nat10fl/fl mice under chow or HFD feeding. Body weight, liver histopathology, and expression of lipid metabolism-associated genes (Srebp1c, Fasn, Pparα, Cd36, Fatp2, Mttp, and Apob) were assessed in male offspring at weaning. Lipid uptake assays were performed both in vivo and in vitro. The mRNA stability assessment and RNA immunoprecipitation were performed to determine NAT10-regulated target genes. RESULTS: NAT10 deletion in hepatocytes of male offspring alleviated perinatal lipid accumulation induced by maternal HFD, decreasing expression levels of Srebp1c, Fasn, Cd36, Fatp2, Mttp, and Apob while enhancing Pparα expression. Furthermore, Nat10HKO male mice exhibited reduced lipid uptake. In vitro, NAT10 promoted lipid uptake by enhancing the mRNA stability of CD36 and FATP2. RNA immunoprecipitation assays exhibited direct interactions between NAT10 and CD36/FATP2 mRNA. CONCLUSIONS: NAT10 deletion in offspring hepatocytes ameliorates maternal HFD-induced hepatic steatosis through decreasing mRNA stability of CD36 and FATP2, highlighting NAT10 as a potential therapeutic target for pediatric MASLD.

Sestrin2 maintains hepatic immune homeostasis and redox balance partially via inhibiting RIPK3-mediated necroptosis in metabolic dysfunction-associated steatohepatitis.

BACKGROUND & AIMS: Necroptosis, a novel type of programmed cell death, is intricately associated with inflammatory response. Currently, most studies focus on the activation of necroptosis, while the mechanisms underlying the negative regulation of necroptosis remain poorly understood. METHODS: The effects of sestrin2 (SESN2) overexpression or knockdown on the regulation of necroptosis were assessed in the TNFα/Smac-mimetic/Z-VAD-FMK (T/S/Z)-induced necroptosis model and palmitic acid (PA)-induced lipotoxicity model. Western-blot, co-Immunoprecipitation, Glutathione S-transferase pull-down, and confocal assays were employed to explore the regulatory mechanisms including protein-protein interactions and post-translational modification. Furthermore, we used GSK'872, a specific inhibitor of receptor-interacting serine/threonine-protein kinase (RIPK) 3, to evaluate the relationship between SESN2-related alterations and RIPK3-mediated necroptosis in T/S/Z-induced necroptosis model, PA-induced lipotoxicity model, and high-fat high-cholesterol diet (HFHCD)-induced non-alcoholic steatohepatitis model. RESULTS: Our findings revealed that SESN2 was upregulated under conditions that induce necroptosis and functioned as a negative regulator of necroptosis. High levels of SESN2 could equipped hepatocytes with the ability to defend against necroptotic inflammation and oxidative stress. Mechanistically, SESN2 interacted with RIPK3 and tuned down necroptosis by inhibiting the phosphorylation of RIPK3, promoting the ubiquitination of RIPK3, and preventing the formation of the RIPK1/RIPK3 necrosome. The depletion of SESN2 resulted in excessive necroptosis, accompanied by increased fat accumulation, inflammation, and oxidative stress in the experimental steatohepatitis model. Blocking necroptosis by GSK'872 reduced the liberation of pro-inflammatory cytokines and reactive oxygen species generation, but not hepatocyte fat deposition, in both PA-treated SESN2 knockout cells and HFHCD-fed SESN2 knockout mice, suggesting that the activation of RIPK3-mediated necroptosis may partially account for the hyperinflammation and excessive oxidative stress induced by SESN2 deficiency. CONCLUSION: Our results suggested that SESN2 inhibited RIPK3-mediated necroptosis; this regulation is an important for the immune homeostasis and the redox balance in the liver.

Head-to-head comparisons of enhanced CT, 68Ga-PSMA-11 PET/CT and 18F-FDG PET/CT in identifying adverse pathology of clear-cell renal cell carcinoma: a prospective study

ABSTRACT Objectives: Accurate preoperative prediction of adverse pathology is crucial for treatment planning of renal cell carcinoma (RCC). Previous studies have emphasized the potential of prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA PET/CT) in differentiating between benign and malignant localized renal tumors. However, there is a scarcity of case reports elucidating the identification of aggressive pathological features using PET/CT. Our study was designed to prospectively compare the diagnostic value of enhanced CT, 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (18F-FDG) PET/CT in clear-cell renal cell carcinoma (ccRCC) with necrosis or sarcomatoid or rhabdoid differentiation. Materials and Methods: A prospective case series of patients with a newly diagnosed renal mass who underwent enhanced CT, 68Ga-PSMA-11 and 18F-FDG PET/CT within 30 days prior to nephrectomy was included. Complete preoperative and postoperative clinicopathological data were recorded. Patients who received neoadjuvant targeted therapy, declined enhanced CT or PET/CT scanning, refused surgical treatment or had non-ccRCC pathological indications were excluded. Radiological parameters were compared within subgroups of pathological characteristics. Bonferroni corrections were used to adjust for multiple testing and statistical significance was set at a p-value less than 0.017. Results: Seventy-two patients were available for the final analysis. Enhanced CT demonstrated poor performance in identifying necrosis, sarcomatoid or rhabdoid differentiation and adverse pathology (all P > 0.05). The maximum standardized uptake value (SUVmax) of 68Ga-PSMA-11 PET/CT was more effective than 18F-FDG PET/CT in identifying tumor necrosis and adverse pathology, with an area under the curve (AUC) of 0.85 (cutoff value=25.26, p<0.001; Delong test z=2.709, p=0.007) for tumor necrosis and AUC of 0.90 (cutoff value=25.26, p<0.001; Delong test z=3.433, p<0.001) for adverse pathology. However, no significant statistical difference was found between 68Ga-PSMA-11 and 18F-FDG PET/CT in predicting sarcomatoid or rhabdoid feature (AUC of 0.91 vs.0.75, Delong test z=1.998, p=0.046). Subgroup analyses based on age, sex, tumor location, maximal diameter, stage and WHO/ISUP grade demonstrated that 68Ga-PSMA-11 PET/CT SUVmax had a significant predictive value for adverse pathology. Enhanced CT value and SUVmax demonstrated strong reliability [intraclass correlation coefficient (ICC) > 0.80], indicating a robust correlation. Conclusions: 68Ga-PSMA-11 PET/CT demonstrates distinct advantages in identifying aggressive pathological features of primary ccRCC when compared to enhanced CT and 18F-FDG PET/CT. Further research and assessment are warranted to fully establish the clinical utility of 68Ga-PSMA-11 PET/CT in ccRCC.

Head-to-head comparisons of enhanced CT, 68Ga-PSMA-11 PET/CT and 18F-FDG PET/CT in identifying adverse pathology of clear-cell renal cell carcinoma: a prospective study.

OBJECTIVES: Accurate preoperative prediction of adverse pathology is crucial for treatment planning of renal cell carcinoma (RCC). Previous studies have emphasized the potential of prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA PET/CT) in differentiating between benign and malignant localized renal tumors. However, there is a scarcity of case reports elucidating the identification of aggressive pathological features using PET/CT. Our study was designed to prospectively compare the diagnostic value of enhanced CT, 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (18F-FDG) PET/CT in clear-cell renal cell carcinoma (ccRCC) with necrosis or sarcomatoid or rhabdoid differentiation. MATERIALS AND METHODS: A prospective case series of patients with a newly diagnosed renal mass who underwent enhanced CT, 68Ga-PSMA-11 and 18F-FDG PET/CT within 30 days prior to nephrectomy was included. Complete preoperative and postoperative clinicopathological data were recorded. Patients who received neoadjuvant targeted therapy, declined enhanced CT or PET/CT scanning, refused surgical treatment or had non-ccRCC pathological indications were excluded. Radiological parameters were compared within subgroups of pathological characteristics. Bonferroni corrections were used to adjust for multiple testing and statistical significance was set at a p-value less than 0.017. RESULTS: Seventy-two patients were available for the final analysis. Enhanced CT demonstrated poor performance in identifying necrosis, sarcomatoid or rhabdoid differentiation and adverse pathology (all P > 0.05). The maximum standardized uptake value (SUVmax) of 68Ga-PSMA-11 PET/CT was more effective than 18F-FDG PET/CT in identifying tumor necrosis and adverse pathology, with an area under the curve (AUC) of 0.85 (cutoff value=25.26, p<0.001; Delong test z=2.709, p=0.007) for tumor necrosis and AUC of 0.90 (cutoff value=25.26, p<0.001; Delong test z=3.433, p<0.001) for adverse pathology. However, no significant statistical difference was found between 68Ga-PSMA-11 and 18F-FDG PET/CT in predicting sarcomatoid or rhabdoid feature (AUC of 0.91 vs.0.75, Delong test z=1.998, p=0.046). Subgroup analyses based on age, sex, tumor location, maximal diameter, stage and WHO/ISUP grade demonstrated that 68Ga-PSMA-11 PET/CT SUVmax had a significant predictive value for adverse pathology. Enhanced CT value and SUVmax demonstrated strong reliability [intraclass correlation coefficient (ICC) > 0.80], indicating a robust correlation. CONCLUSIONS: 68Ga-PSMA-11 PET/CT demonstrates distinct advantages in identifying aggressive pathological features of primary ccRCC when compared to enhanced CT and 18F-FDG PET/CT. Further research and assessment are warranted to fully establish the clinical utility of 68Ga-PSMA-11 PET/CT in ccRCC.

Head-to-head comparisons of 68Ga-PSMA-11 and 18F-FDG PET/CT in evaluating patients with upper tract urothelial carcinoma: a prospective pilot study.

PURPOSE: To prospectively compare the uptake of 68Ga-prostate specific membrane antigen (68Ga-PSMA)-11 and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in upper tract urothelial carcinoma (UTUC) and investigate the correlation between radiological parameters and pathological features of UTUC. METHODS: Clinicopathologic and imaging data were collected from 10 UTUC patients who underwent preoperative 68Ga-PSMA-11 and 18F-FDG PET/CT scans. The diagnostic capabilities of both imaging techniques were analyzed and compared in UTUC. Angiogenesis in the malignancies was assessed using Chalkley counting and the expression of folate hydrolase 1 (FOLH1) and glucose transporter 1 (GLUT1) in UTUC were evaluated in the surgical specimens. Double immunofluorescence staining of PSMA and CD34 was used to examine tumor neovascularization. Tracer uptake and expression were compared and explored. Additionally, 10 patients with clear cell renal cell carcinoma (ccRCC) were included for prospective, comparative research. RESULTS: Ten UTUC patients with 12 malignant lesions and another 10 ccRCC patients were included. 18F-FDG PET/CT demonstrated a more effective detection of UTUC foci compared to 68Ga-PSMA-11 PET/CT (the SUVmax of 18.48 ± 6.73 vs. 4.38 ± 1.45, P < 0.01). Immunohistochemical analysis revealed a statistically significant difference in the expression of PSMA and GLUT1 in UTUC (P = 0.048), with higher pathological grades showing more intense GLUT1 staining than PSMA (75% vs. 12.5%). The Chalkley counting of angiogenesis in ccRCC was significantly higher than that in UTUC (229.34 vs. 71.67), which was proportional to 68Ga-PSMA-11 PET/CT SUVmax (both P < 0.05). CONCLUSION: 18F-FDG PET/CT holds better clinical potential for evaluating UTUC and detecting lymph node metastasis compared to 68Ga-PSMA-11 PET/CT, likely due to the relatively scant expression of FOLH1 in tumor neovascular endothelium while the abundant expression of GLUT1 in malignancy. Furthermore, the lower neovascular density in UTUC should not be overlooked.

Effect of tanshinone IIA for myocardial ischemia/reperfusion injury in animal model: preclinical evidence and possible mechanisms.

Introduction: Tanshinone IIA (Tan IIA), the major active lipophilic ingredient of Radix Salviae Miltiorrhizae, exerts various therapeutic effects on the cardiovascular system. We aimed to identify the preclinical evidence and possible mechanisms of Tan IIA as a cardioprotective agent in the treatment of myocardial ischemia/reperfusion injury. Methods: The study quality scores of twenty-eight eligible studies and data analyses were separately assessed using the CAMARADES 10-item checklist and Rev-Man 5.3 software. Results: The study quality score ranged from 3/10 to 7/10 points. The present study provided preliminary preclinical evidence that Tan IIA could significantly decrease the myocardial infarct size, cardiac enzyme activity and troponin levels compared with those in the control group (p < 0.05). Discussion: Tan IIA alleviated myocardial I/R injury via antioxidant, anti-inflammatory, anti-apoptosis mechanisms and improved circulation and energy metabolism. Thus, Tan IIA is a promising cardioprotective agent for the treatment of myocardial ischemia/reperfusion injury and should be further investigated in clinical trials.

Semantic Computed Tomography Features for Predicting BRCA1-associated Protein 1 and/or Tumor Protein p53 Gene Mutation Status in Clear Cell Renal Cell Carcinoma.

PURPOSE: The purpose of this study was to explore the semantic computed tomography (CT) features associated with BRCA1-associated protein 1 (BAP1) and/or tumor protein p53 (TP53) mutation in clear cell renal cell carcinoma (ccRCC). METHODS AND MATERIALS: Clinical characteristics and gene mutation information of 336 ccRCC patients were retrieved from The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma database (TCGA-KIRC). Kaplan-Meier analysis was performed to examine prognosis by gene mutation. The CT imaging data and gene mutation information of 156 ccRCC patients treated between January 2019 and January 2021 (the training cohort) were retrospectively analyzed. The CT imaging information and gene mutation data of 123 patients with ccRCC were downloaded from The Cancer Imaging Archive and The Cancer Genome Atlas database (the external validation cohort). Univariate Chi-square test and multivariate binary logistic regression analysis were performed to determine predictors of gene mutation; a nomogram was developed using these predictors. Receiver operating characteristic curve analysis and the Hosmer-Lemeshow test were performed to evaluate the performance of the nomogram. RESULTS: Kaplan-Meier analysis showed that BAP1 and/or TP53 mutation was significantly correlated with worse survival outcome. Multivariate binary logistic regression analysis indicated ill-defined margin (P = .001), spiculated margin (P = .018), renal vein invasion (P = .002), and renal pelvis invasion (P = .001) were independent predictors of BAP1 and/or TP53 mutation. A nomogram containing these 4 semantic CT features was constructed; the area under the receiver operating characteristic curves was 0.872 (95% CI, 0.809-0.920). The Hosmer-Lemeshow test showed acceptable goodness-of-fit for the nomogram (X2 = 1.194, P = .742). The nomogram was validated in the validation cohort; it showed good accuracy (area under the receiving operating characteristic curve = 0.819, 95% CI, 0.740-0.883) and was well calibrated (X2 = 3.934, P = .559). CONCLUSIONS: Semantic CT features are a potential and promising method for predicting BAP1 and/or TP53 mutation status in ccRCC patients.

Early-life exposure to gestational diabetes mellitus predisposes offspring to pediatric nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) has emerged as the prevailing chronic liver disease in the pediatric population due to the global obesity pandemic. Evidence shows that prenatal and postnatal exposure to maternal abnormalities leads to a higher risk of pediatric NAFLD through persistent alterations in developmental programming. Gestational diabetes mellitus (GDM) is a hyperglycemic syndrome which has become the most prevalent complication in pregnant women. An increasing number of both epidemiologic investigations and animal model studies have validated adverse and long-term outcomes in offspring following GDM exposure in utero. Similarly, GDM is considered a crucial risk factor for pediatric NAFLD. This review aimed to summarize currently published studies concerning the inductive roles of GDM in offspring NAFLD development during childhood and adolescence. Dysregulations in hepatic lipid metabolism and gut microbiota in offspring, as well as dysfunctions in the placenta are potential factors in the pathogenesis of GDM-associated pediatric NAFLD. In addition, potentially effective interventions for GDM-associated offspring NAFLD are also discussed in this review. However, most of these therapeutic approaches still require further clinical research for validation.

The burden and sexual dimorphism with nonalcoholic fatty liver disease in Asian children: A systematic review and meta-analysis.

BACKGROUND: Despite substantial attention paid to the epidemic of nonalcoholic fatty liver disease (NAFLD) in adults, data on the burden and sexual dimorphism of NAFLD in Asian children have not yet been synthesized. METHODS: We conducted a literature search of 735 references up to April 2021. Pooled analyses, stratified analyses and meta-regression were all performed. RESULTS: Thirty-three study populations were finally included. Nine of them comprising 20 595 children showed an overall NAFLD prevalence of 5.53% (95% CI 3.46%-8.72%), in which, 36.64% (95% CI, 27.99%-46.26%) NAFLD subjects had elevated levels of ALT. The prevalence rate of NAFLD increased about 1.6-fold from 2004 to 2010 to the last decade. Male predominant trends were observed in paediatric NAFLD (boys: 8.18%, 95% CI 4.93%-13.26%; girls: 3.60%, 95% CI 1.60%-7.87%). Moreover, meta-analysis showed that after 10 years of age, boys were more prone to have NAFLD than girls (OR = 1.75; P = .0012). In addition, the pooled prevalence of NAFLD increased sequentially in normal-weight (1.49%, 95% CI 0.88%-2.51%, n = 2610), overweight (16.72%, 95% CI 7.07%-34.65%, n = 1265) and obese children (50.13%, 95% CI 41.99%-58.27%, n = 6434 individuals). After full covariate adjustment, the multivariate meta-regression also showed that boy percentage (P = .0396) and body mass index (P < .0001) were positively correlated with prevalent NAFLD. CONCLUSIONS: In Asia, paediatric NAFLD is becoming prevalent over the recent decades, particularly among obese children and boys after 10 years old. The hormonal and chromosomal origins of paediatric NAFLD dimorphism need further investigation.

Escherichia fergusonii Promotes Nonobese Nonalcoholic Fatty Liver Disease by Interfering With Host Hepatic Lipid Metabolism Through Its Own msRNA 23487.

BACKGROUND & AIMS: Gut microbiota and microbial factors regulate the pathogenesis of nonalcoholic fatty liver disease (NAFLD) in patients with obesity and metabolic abnormalities, but little is known about their roles in nonobese NAFLD. Expansion of Escherichia is associated with NAFLD pathogenesis. We aimed to investigate the pathogenic role of Escherichia fergusonii and its products in the development of nonobese NAFLD. METHODS: We characterized the intestinal microbiome signature in a cohort of NAFLD patients and healthy controls by 16S ribosomal RNA sequencing. The role of E fergusonii was estimated in rats after 16 weeks of administration, and features of NAFLD were assessed. E fergusonii-derived microRNA-sized, small RNAs (msRNAs) were analyzed by deep sequencing. RESULTS: We detected an expansion of Escherichia_Shigella in NAFLD patients compared with healthy controls, and its increase was associated with disease severity independent of obesity. E fergusonii, a member of the genus Escherichia, induced the development of nonobese NAFLD characterized by hepatic steatosis and hepatocyte ballooning in rats without obesity. It disturbed host lipid metabolism by inhibiting hepatic lipid ß-oxidation and promoting de novo lipogenesis. We also showed that E fergusonii caused the development of hepatic inflammation and fibrosis in a sizable fraction of animals at an advanced stage of NAFLD. Mechanistically, E fergusonii-derived msRNA 23487 down-regulated host hepatic peroxisome proliferator-activated receptor α expression, which could contribute to lipid accumulation in the liver. CONCLUSIONS: These results suggest that E fergusonii promotes the pathogenesis of steatohepatitis and fibrosis in nonobese rats by secreting msRNA 23487, and it might be a potential biomarker for predicting steatohepatitis in nonobese NAFLD.

[Meta-analysis of Tanreqing Injection in adjuvant treatment of stroke-associated pneumonia].

To systematically evaluate the efficiency and safety of Tanreqing Injection in the treatment of stroke-associated pneumonia(SAP). Seven domestic and foreign databases(CNKI, Wanfang, VIP, CBM, PubMed, Cochrane Library, EMbase) were retrieved from the establishment to July 2020. According to the inclusion and exclusion criteria, randomized controlled trial of the effect of Tanreqing Injection in the treatment of SAP was selected. NoteExpress software was used to screen out literatures. RevMan 5.4 software was used for data analysis. GRADE system was used to evaluate the evidence quality of the outcome indicators. A total of 1 755 cases in 21 studies were retrieved, including 879 cases in experimental group and 876 cases in control group. In general, the quality of stu-dies received was not high. According to Meta-analysis,(1) in terms of shortening the length of hospital stay, Tanreqing Injection combined with conventional western medicine was better than conventional western medicine(MD=-4.04, 95%CI[-4.43,-3.65], P<0.000 01);(2) in terms of increasing effective rate, Tanreqing Injection combined with conventional western medicine was better than conventional western medicine(RR=1.22, 95%CI[1.17, 1.27], P<0.000 01);(3) in terms of reducing inflammation indicators, Tanreqing Injection combined with conventional western medicine was better than conventional western medicine(MD_(CRP)=-10.75, 95%CI[-15.61,-5.88], P<0.000 01; MD_(WBC count)=-1.62, 95%CI[-2.55,-0.69], P=0.000 6; MD_(PCT)=-0.58, 95%CI[-0.89,-0.26], P=0.000 3];(4) in terms of improving symptoms and signs, Tanreqing Injection combined with conventional wes-tern medicine was better than conventional western medicine(MD_(cough)=-2.73, 95%CI[-4.93,-0.53], P=0.02; MD_(antipyretic)=-1.07, 95%CI[-1.17,-0.98), P<0.000 01];(5) in terms of decreasing the NIHSS scores, Tanreqing Injection combined with conventional western medicine was better than conventional western medicine(MD=-3.02, 95%CI[-4.91,-1.13], P=0.002);(6) in terms of adverse reactions, there was no statistically significant difference between Tanreqing Injection combined with conventio-nal western medicine compared with conventional western medicine treatment(RR=1.19, 95%CI[0.61,2.29], P=0.61). GRADE system showed that the evidence levels of above outcome indicators were low and extremely low. The results proved that Tanreqing Injection combined with conventional western medicine had a good advantage in the treatment of SAP, with better observation indicators better than western medicine conventional treatment, and no increase in the incidence of adverse reactions. However, this study had certain limitations. The overall quality of the included studies was low, which affected the reliability of the results. Therefore, the conclusions of this study shall be used cautiously.

16S ribosomal RNA sequencing reveals a modulation of intestinal microbiome and immune response by dietary L-theanine supplementation in broiler chickens.

Despite the availability of abundant literature on green tea, studies on the use of L-theanine (an amino acid found only in green tea) as a feed additive in poultry especially broiler are limited. So, this study was conducted to explore the effects of L-theanine on the intestinal microbiome and immune response in a broiler. A total of 400-d-old chicks were randomly divided into four treatment groups (A, B, C, and D) using a complete randomized design. Treatments were as follows: A, control (basal diet); B, basal diet + 100 mg L-theanine/kg diet; C, basal diet + 200 mg L-theanine/kg diet; and D, basal diet + 300 mg L-theanine/kg diet. Mucosal samples from ileum and jejunum of broiler chicken were extracted at 21 and 42 d of age. Extraction of genomic DNA was followed by amplification of V3 and V4 hypervariable regions of 16S ribosomal RNA. After Illumina sequencing, results revealed that treatment with L-theanine significantly increased the population of Lactobacillus in ileum and jejunum as compared to a control group, but the higher population was observed in jejunum at both 21 and 42 d of age. The overall diversity of the jejunum microbiome in the treatment group was significantly lower than that of the ileum and control group (P < 0.05). Results of this study revealed that mRNA expression of TLRs (TLR-2 and TLR-4) and cytokines (TNF-α, IFN-γ, and IL-2) was decreased in response to treatment with L-theanine. Moreover, the negative correlation of abundance of Lactobacillus was observed with expression of IL-2 and IFN-γ in the intestine and these effects were highly significant (P < 0.01). In summary, our finding revealed that dietary supplementation of L-theanine exhibited a positive influence on intestinal bacteria by supporting beneficial microbes like Lactobacillus while decreasing harmful microbes like Clostridium.