Objective: To provide the mechanism-based pharmacotherapy of the Huatan Qushi formula (HTQS formula), for the health management and treatment of non-alcoholic fatty liver disease (NAFLD). Methods: A rat model of NAFLD was employed to examine the efficacy and safety of the HTQS formula. In vivo active components and potential mechanisms of the HTQS formula were identified using UPLC‒MS/MS combined with network pharmacology. The influence of the HTQS formula on the dominating proteins in PI3K/Akt pathway was validated in vivo using western blot. Finally, 16S rRNA sequencing of the gut microbiome was conducted followed by targeted metabolomics detecting fecal short-chain fatty acids (SCFAs) and bile acids to determine the impact of the HTQS formula on gut microbiota. Results: The HTQS formula reduced weight gain and hepatic steatosis in NAFLD rats and decreased serum total cholesterol (TC), triglycerides, blood glucose, and insulin resistance (IR) without causing liver or kidney injury. We detected 28 components using UPLC‒MS/MS and identified 439 shared targets between NAFLD and the HTQS formula. Primarily, we focused on the PI3K/Akt signaling pathway based on protein‒protein interaction network analysis. We validated that the HTQS formula inhibited liver steatosis and inflammation by increasing the phosphorylation levels of PI3K, AKT, P27, GSK3β in the PI3K/Akt signaling pathway. 16S rRNA sequencing revealed that the HTQS formula reduced the abundance of the genus Family_XIII_AD3011_group, which was positively correlated with IR and taurodeoxycholic acid. In addition, Lachnospiraceae_UCG_010 inversely correlated with TC and five bile acids, which could be essential to the therapeutic effect of the HTQS formula against NAFLD. Conclusions The HTQS formula proved to be an effective pharmacotherapy for NAFLD without causing liver or kidney injury. Multiple potent components of the HTQS formula could alleviate liver steatosis and lipid metabolism disorder by modulating the PI3K/Akt signaling pathway and restoring gut microbiota composition.

Background::Heterogeneity of tumor cells and the tumor microenvironment (TME) is significantly associated with clinical outcomes and treatment responses in patients with urothelial carcinoma (UC). Comprehensive profiling of the cellular diversity and interactions between malignant cells and TME may clarify the mechanisms underlying UC progression and guide the development of novel therapies. This study aimed to extend our understanding of intra-tumoral heterogeneity and the immunosuppressive TME in UC and provide basic support for the development of novel UC therapies.Methods::Seven patients with UC were included who underwent curative surgery at our hospital between July 2020 and October 2020. We performed single-cell RNA sequencing (scRNA-seq) analysis in seven tumors with six matched adjacent normal tissues and integrated the results with two public scRNA-seq datasets. The functional properties and intercellular interactions between single cells were characterized, and the results were validated using multiplex immunofluorescence staining, flow cytometry, and bulk transcriptomic datasets. All statistical analyses were performed using the R package with two-sided tests. Wilcoxon-rank test, log-rank test, one-way analysis of variance test, and Pearson correlation analysis were used properly.Results::Unsupervised t-distributed stochastic neighbor embedding clustering analysis identified ten main cellular subclusters in urothelial tissues. Of them, seven urothelial subtypes were noted, and malignant urothelial cells were characterized with enhanced cellular proliferation and reduced immunogenicity. CD8 + T cell subclusters exhibited enhanced cellular cytotoxicity activities along with increased exhaustion signature in UC tissues, and the recruitment of CD4 + T regulatory cells was also increased in tumor tissues. Regarding myeloid cells, coordinated reprogramming of infiltrated neutrophils, M2-type polarized macrophages, and LAMP3 + dendritic cells contribute to immunosuppressive TME in UC tissues. Tumor tissues demonstrated enhanced angiogenesis mediated by KDR + endothelial cells and RGS5 +/ACTA2 + pericytes. Through deconvolution analysis, we identified multiple cellular subtypes may influence the programmed death-ligand 1 (PD-L1) immunotherapy response in patients with UC. Conclusion::Our scRNA-seq analysis clarified intra-tumoral heterogeneity and delineated the pro-tumoral and immunosuppressive microenvironment in UC tissues, which may provide novel therapeutic targets.

Objective:To evaluate the value and identify the prognosic factors of postoperative radiotherapy (PORT) in completely resected stage Ⅲ(pN 2) lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) wild-type who received adjuvant chemotherapy. Methods:Clinical data of 172 patients with stage Ⅲ(pN 2) EGFR wild-type lung adenocarcinoma who underwent radical resection and adjuvant chemotherapy from 2009 to 2016 were retrospectively analyzed. All patients received platinum-based adjuvant chemotherapy combining two drugs for>4 cycles, and divided into the PORT group and the non-PORT group. The survival rate was calculated by Kaplan- Meier method and log-rank test, and multivariate prognostic analysis was performed by Cox’s regression model. Results:Among 172 patients, the median overall survival (OS), 3-year and 5-year OS rates were 40 months, 55.9% and 28.3%, respectively. The median disease-free survival (DFS), 3-year and 5-year DFS rates were 17 months, 24.5% and 13.0%, respectively. DFS was significantly improved in the PORT group (29 months vs. 13 months, P=0.001), whereas OS did not significantly differ between two groups (51 months vs. 38 months, P=0.151). In subgroup analysis, DFS of patients with multistation N 2 or the number of N 2 metastases of≥3 or skip N 2 in the PORT group was significantly longer ( P<0.05), whereas PORT exerted no significant effect on OS ( P>0.05). Conclusions:For patients with completely resected stage Ⅲ(N 2) EGFR wild-type lung adenocarcinoma receiving adjuvant chemotherapy, PORT might increase DFS and have a trend toward longer OS. However, these findings remain to be validated by large sample size investigations.

Background: Metabolic diseases pose considerable burden on the healthcare system worldwide, indi-cating the significance of prevention and treatment. In constitution theory of traditional Chinese med-icine, phlegm-dampness constitution (PDC) is the common basis of metabolic diseases. In clinical practice, Huatan Qushi (HTQS) decoction targeting on PDC can effectively improve metabolic indicators. However, its underlying biochemical mechanism still remains unclear.Methods: Eight PDC participants received HTQS decoction for three months. Their blood was collected at baseline and 1 and 3 months after intervention started. Related biomedical indicators were detected. High-throughput sequencing and RT-qPCR were used for validation. Due to the missing data, repeated measures with missing values in mixed models were used. Results: After 3-month treatment, HDL-C level increased (P<.001) and FBG, FINS, and HbA1c all showed decreasing trend at different time points (all P < .05). After miRNA high-throughput sequencing, compared with the baseline, differential miRNAs at 1 and 3 months were screened, and target gene prediction and KEGG pathway enrichment analysis were performed. The results displayed that metabolic disease-related pathways mainly included pathways in cancer, PI3K-Akt signaling pathway, etc. Further, RT-qPCR showed that hsa-miR-1237-3p differed statistically (P =.008). Then we validated the target genes of hsa-miR-1237-3p in the"Pathways in Cancer"pathway including SDF1, AC, CRK, and HGF, also known as upstream target genes of PI3K/AKT pathway. The results showed that two indicators of CRK and HGF were in statistical significance (P=.045 and P=.036, respectively). Conclusion: PDC serves as a common basis for various metabolic diseases. Through adjusting PDC, HTQS decoction can improve biomedical indicators including blood glucose, HbA1c, insulin, and HDL-C. The target pathway is"Pathways in cancer". Specifically, HTQS decoction acts on targets of CRK and HGF by regulating hsa-miR-1237-3p, and probably exerts effects on their downstream PI3K/AKT pathway.

Objective To investigate the clinical characteristics of invasive fungal infections(IFI) in PICU and analyze the risk factors for diagnosis and treatment earlier.Methods The clinical data of patients with IFI hospitalized in PICU from January 2013 to December 2017 were retrospectively studied.Results There were 179 cases of patients with positive fungal cultures,of which 49 cases were IFI.There were 23 males and 26 females,the mean age was (3.87 ± 2.42) years.A total of 47 cases had underlying diseases.In positive specimen,there were 36 cases of bronchoalveolar lavage fluid or sputum cultures,14 cases of blood cultures,7 cases of urinary cultures,3 cases of thoracic/ascites cultures,2 cases of bone marrow cultures,and 1 case of cerebrospinal fluid culture.There were 12 cases who had at least two sites infection at the same time.A total of 53 strains of fungal pathogens were cultivated,among which 45 cases were candida,5 cases were aspergillus,and 3 cases were penicillium marneffei,and 4 cases had two fungal infections.The presence of underlying diseases,blood transfusions,use of antibiotics/glucocorticoids/immunosuppressors,invasive procedures,and long hospital stays were risk factors (all P ＜ 0.05).Drug susceptibility analysis showed that all strains were sensitive to antifungal drugs of amphotericin B/liposomes,azoles and echinocandins,except 1 case of Candida utilis,1 case of Saccharomyces cerevisiae and 1 case of Candida lusitaniae.There were 26 patients only treated with one antifungal drug and 23 had combined drugs.All patients had fever.Eleven patients developed multiple organ dysfunction syndrome and 6 died.Conclusion There are no specific clinical manifestations for children with IFI and with critical condition and high mortality.Candida is the most common fungal infection.The lung is the most common part of infection.The children of IFI with risk factors such as underlying diseases,blood transfusions,use of antibiotics/glucocorticoids/immunosuppressors,invasive procedures and long hospital stays,should be identified in combination with laboratory examination and use antifungal drugs rationally as early as possible.

Objective    To investigate the learning curve of non-tube and early oral feeding procedure following McKeown minimally invasive esophagectomy (MIE). Methods    We analyzed the clinical data of 38 patients (26 males, 12 females, aged 42–79 years) with esophageal cancer who received non-tube and early oral feeding procedure after surgery at the Affiliated Tumor Hospital, Zhengzhou University from November 2017 to August 2018. They suffered upper thoracic esophageal cancer (n=4), middle thoracic esophageal cancer (n=22) or lower thoracic esophageal cancer (n=12). Results    McKeown MIE was successfully performed on 38 patients. Oral feeding began 1.7 (1-4) days after surgery in the 38 patients with non-tube. Pneumonia/atelectasis occurred in 5 patients (13.1%), respiratory failure in 1 patient (2.6%), arrhythmia in 3 patients (7.9%), hoarseness in 5 patients (13.1%), anastomotic fistula in 1 patient (2.6%), cervical incision infection in 1 patient (2.6%), pneumomediastinum and infection in 1 patient (2.6%) and gastric emptying disorder in 2 patients (5.2%). No death was observed. After 26 patients with McKeown MIE were treated with enhanced recovery after surgery procedure, the operation time and complications could reach a relatively stable state and entered a plateau phase of learning curve. Conclusion    Non-tube and early oral feeding procedure following MIE is technically safe and feasible. It can shorten hospital stay, relieve the discomfort of placement of nasogastric and nutrition tube and may reduce the incidence of complications. The learning curve of non-tube and early oral feeding procedure following MIE is  about 26 cases.

Objective To describe the effects of surgical intervention on the prognosis in non-small-cell lung cancer patients with pleural carcinomatosis detected at thoracotomy.Methods Retrospectively analyzed clinical data from 54 patients who have unexpected malignant pleural nodules and/or malignant pleural effusions first detected at thoracotomy from January 2009 and December 2013.The effects of surgical intervention on the prognosis were also discussed.Results Sixteen cases had only biopsy,whereas 38 (70.4％) cases had primary tumor resection.The median survival time of 54 patients with pleural carcinomatosis were 23 months.The overall 1 and 5-year survival rates were 64％ and 18％,respectively.Primary tumor resection had significantly better outcome compared with biopsy(MST:respectively,24 vs 15 months,5-year survival rate 39％ vs 6％,P ＜0.05).Univariate analysis showed that primary tumor resection,no smoking history,lower T and N stage has favorable survival(P ＜ 0.05).Multivariate analysis showed that the best N stage(P =0.002) and adenocarcinoma(P =0.035) were favorable prognostic factors in these patients.Conclusion For patients with pleural careinomatosis first detected at thoracotomy,limited primary tumor resection may have survival benefits,lower T and N stage for them was associated with better survival.

Objective To evaluate pathogens and antimicrobial resistance of pathogens causing refractory pneumonia in children.Methods Children with refractory pneumonia who admitted to a hospital between May 2008 and December 2014 were performed bronchoscopy,and bronchoalveolar lavage fluid (BALF)were performed bacterial culture and antimicrobial resistance testing.Results 1 693 patients were recruited in the study,273 bacterial isolates were isolated from BALF speci-mens of 226 children,gram-positive bacteria accounted for 38.10% (104/273 ),the main gram-positive bacteria were Streptococcus pneumoniae (n=71)and Staphylococcus aureus (n=23);gram-negative bacteria accounted for 58.24%(159/273),including 44 isolates of Haemophilus parainfluenzae ,28 Klebsiella pneumoniae ,19 Escherichia coli ,and 17 Pseud-omonas aeruginosa ;10 isolates of fungi were also detected,8 of which were Candida albicans .The sensitivity of Streptococ-cus pneumoniae to quinolones,ceftriaxone and cefotaxime were high.Methicillin-resistant Staphylococcus aureus (MRSA) positive rate was 26.32%.ESBLs-producing rate of Haemophilus parainfluenzae and Klebsiella pneumoniae was 32.72% and 62.96% respectively.Conclusion The major pathogens causing refractory pneumonia were Streptococcus pneumoniae and Haemophilus parainfluenzae ,empirical treatment should be conducted accordingly,antimicrobial resist-ance should be considered if therapeutic effect is poor,and targeted therapy should be performed according to cultured re-sults and antimicrobial susceptibility testing result.

Objective To finding out the characters of vascular remolding after the establishment of native arteriovenous fistula on the wrist,and exploring the influential factors.Methods Doppler ultrasound was used to monitor the diameter of cephalic vein,brachial artery,radial artery and ulnar artery at the time before the surgery and one day,one week,two weeks,four weeks and eight weeks after the surgery respectively.The tendency of the diameter change was analyzed.Results Twenty eight patients completed the whole monitor session,in which eleven were female.The average age of those patients was (53.68 ± 2.61) years old.Twelve of them were diabetic nephropathy.The diameters of all vessel were increased more rapidly at the first day than any other days after surgery(all P ＜ 0.01).The patients were divided into two groups depending on whether diabetic nephropathy.No significant difference was found between the two groups on the tendency of diameter change in cephalic vein and brachial artery (all P ＞ 0.05).However,the tendency of diameter change in radial artery and ulnar artery was statistically significant difference between the two groups (all P ＜ 0.05).Conclusions Cephalic vein,brachial artery,radial artery and ulnar artery are all apparently dilated on the first day after the surgery.The vascular dilation and diameter increasing become much slower after the period,the diameter tend to be stable.The primary diseases may affect the tendency of the diameter change in radial artery as well as ulnar artery.

Objective: In China, doctors at TCM hospitals and clinics often divide patients with a Western medicine (WM) disease into several syndrome classes from the TCM perspective and treat patients in different classes using different principles. A key problem is how to carry out the classification properly. We propose an evidence-based ap-proach for solving the problem where evidence is obtained by analyzing unlabeled symptom data using latent tree models.Method: In previous work, we have shown how latent tree analysis of symptom data can be used to identify TCM syndrome classes among patients with a WM disease. In the paper, we investigate how to establish classification rules for distinguishing between the classes.Results: We have applied the method to a data set about Vascular Mild Cognitive Impairment that involves 93 symptoms and 803 patients. Nine syndrome types are identified, along with the corresponding classification rules. Conclusions: An evidence-based approach to the TCM patient classification prob-lem has been developed. The approach can be used to answer the following questions about a WM disease: What TCM syndrome classes are there? What are the sizes of the classes? What are the statistical characteristics of each class? How can one differentiate between the different classes?