Aim To design and synthesize a series of phenylacetamide derivatives with different substituted phenylacetic acid as raw materials,and to investigate the protective effects of the compound on the damage of pancreatic β cells induced by palmitate acid(PA).Methods Min6 cells were cultured and divided into B blank control group,PA treatment group and PA+compounds group.The viability of Min6 cells was de-tected by CCK-8.The protein expressions of TXNIP and NLRP3 were observed by Western blot.MDA con-tent and SOD activity were detected by MDA and SOD kit.The insulin secretion of Min6 islet cells was meas-ured with insulin ELISA kit.Results A total of 10 phenylacetamide derivatives were designed and synthe-sized.Their structures were confirmed by 1H NMR and ESI-MS.Pharmacological activity study showed that most of the compounds had protective effects on islet βcells,among which LY-6 and LY-8 had stronger pro-tective effects than PA model group,with the cell via-bility of 61.4％,and LY-6 had the highest cell activi-ty,reaching to 104.9％.Compared with PA group,the protein expression of TXNIP and NLRP3 decreased in LY-6 and LY-8 groups,MDA content decreased and SOD activity increased,and insulin secretion of Min6 cell increased.Conclusions LY-6 and LY-8 inhibit TXNIP expression and decrease the activation of NL-RP3 inflammasome,and decrease the production of MDA and increase SOD activity,and thus reducing is-let β cells apoptosis and increasing insulin secretion.Therefore,the compound LY-6 could serve as a poten-tial anti-diabetic new chemical entity.

The odor fingerprint of Pollygonati Rhizoma samples with different mildewing degrees was analyzed and the relationship between the odor variation and the mildewing degree was explored. A fast discriminant model was established according to the response intensity of electronic nose. The α-FOX3000 electronic nose was applied to analyze the odor fingerprint of Pollygonati Rhizoma samples with different mildewing degrees and the radar map was used to analyze the main contributors among the volatile organic compounds. The feature data were processed and analyzed by partial least squares discriminant analysis(PLS-DA), K-nearest neighbor(KNN), sequential minimal optimization(SMO), random forest(RF) and naive Bayes(NB), respectively. According to the radar map of the electronic nose, the response values of three sensors, namely T70/2, T30/1, and P10/2, increased with the mildewing, indicating that the Pollygonati Rhizoma produced alkanes and aromatic compounds after the mildewing. According to PLS-DA model, Pollygonati Rhizoma samples of three mildewing degrees could be well distinguished in three areas. Afterwards, the variable importance analysis of the sensors was carried out and then five sensors that contributed a lot to the classification were screened out: T70/2, T30/1, PA/2, P10/1 and P40/1. The classification accuracy of all the four models(KNN, SMO, RF, and NB) was above 90%, and KNN was most accurate(accuracy: 97.2%). Different volatile organic compounds were produced after the mildewing of Pollygonati Rhizoma, and they could be detected by electronic nose, which laid a foundation for the establishment of a rapid discrimination model for mildewed Pollygonati Rhizoma. This paper shed lights on further research on change pattern and quick detection of volatile organic compounds in moldy Chinese herbal medicines.
Electronic Nose ; Odorants/analysis* ; Volatile Organic Compounds/analysis* ; Bayes Theorem ; Drugs, Chinese Herbal/analysis* ; Discriminant Analysis

Objective: To analyze the clinical presentation and progression risk factors of patients with monoclonal gammopathy of undetermined significance (MGUS) in China. Methods: We retrospectively assessed the clinical features and disease progression of 1 037 patients with monoclonal gammopathy of undetermined significance between January 2004 and January 2022 at Peking Union Medical College Hospital. Results: A total of 1 037 patients were recruited in the study, including 636 males (63.6%) , with a median age of 58 (18-94) years. The median concentration of serum monoclonal protein was 2.7 (0-29.4) g/L. The monoclonal immunoglobulin type was IgG in 380 patients (59.7%) , IgA in 143 patients (22.5%) , IgM in 103 patients (16.2%) , IgD in 4 patients (0.6%) , and light chain in 6 patients (0.9%) . 171 patients (31.9%) had an abnormal serum-free light chain ratio (sFLCr) . According to the Mayo Clinic model for risk of progression, the proportion of patients in the low-risk, medium-low-risk, medium-high risk, and high-risk groups were 254 (59.5%) , 126 (29.5%) , 43 (10.1%) , and 4 (0.9%) , respectively. With a median follow-up of 47 (1-204) months, 34 of 795 patients (4.3%) had disease progression, and 22 (2.8%) died. The overall progression rate was 1.06 (0.99-1.13) /100 person-years. Patients with non-IgM MGUS have a markedly higher disease progression rate per 100 person-years than IgM-MGUS (2.87/100 person-years vs 0.99/100 person-years, P=0.002) . The disease progression rate per 100 person-years in non-IgM-MGUS patients of Mayo classification low-risk, medium-low risk and medium-high risk groups were 0.32 (0.25-0.39) /100 person-years, 1.82 (1.55-2.09) /100 person-years, and2.71 (1.93-3.49) /100 person-years, which had statistically difference (P=0.005) . Conclusion: In comparison to non-IgM-MGUS, IgM-MGUS has a greater risk of disease progression. The Mayo Clinic progression risk model applies to non-IgM-MGUS patients in China.
Male ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Monoclonal Gammopathy of Undetermined Significance ; Retrospective Studies ; Risk Factors ; Immunoglobulin Light Chains ; Disease Progression

To explore the composition and diversity of the intestinal microflora of Leopoldamys edwardsi in Hainan Island. In November 2019, DNA was extracted from fecal samples of 25 adult Leopoldamys edwardsi (14 males and 11 females) in Hainan Island at the Joint Laboratory of tropical infectious diseases of Hainan Medical College and Hong Kong University. Based on the IonS5TMXL sequencing platform, single-end sequencing (Single-End) was used to construct a small fragment library for single-end sequencing. Based on Reads shear filtration and OTUs clustering. The species annotation and abundance analysis of OTUs were carried out by using mothur method and SSUrRNA database, and further conducted α diversity and β diversity analysis. A total of 1481842 high quality sequences, belonging to 14 Phyla, 85 families and 186 Genera, were obtained from 25 intestinal excrement samples of Leopoldamys edwardsi. At the level of phyla classification, the main core biota of the Leopoldamys edwardsi contained Firmicutes (46.04%),Bacteroidetes (25.34%), Proteobacteria (17.09%), Tenericutes (7.38%) and Actinobacteria (1.67%), these five phyla account for 97.52% of all phyla. The ratio of Helicobacter which occupied the largest proportion at the genus level was 12.44%, followed by Lactobacillus (11.39%), Clostridium (6.19%),Mycoplasma (4.23%) and Flavonifractor (3.52%). High throughput sequencing analysis showed that the intestinal flora of Leopoldamys edwardsi in Hainan Island was complex and diverse, which had the significance of further research.
Adult ; Animals ; Bacteria/genetics* ; Feces/microbiology* ; Female ; Gastrointestinal Microbiome/genetics* ; High-Throughput Nucleotide Sequencing ; Humans ; Intestines ; Male ; Murinae/genetics*

Objective: To provide reference and evidence for clinical application of neoadjuvant immunotherapy in patients with colorectal cancer through multicenter large-scale analysis based on real-world data in China. Methods: This was a retrospective multicenter case series study. From January 2017 to October 2021, data of 94 patients with colorectal cancer who received neoadjuvant immunotherapy in Peking University Cancer Hospital (55 cases), Union Hospital of Tongji Medical College of Huazhong University of Science and Technology (19 cases), Sun Yat-sen University Cancer Center (13 cases) and Changhai Hospital of Navy Medical University (7 cases) were retrospectively collected, including 48 males and 46 females. The median age was 58 years. Eighty-one cases were rectal cancer and 13 cases were colon cancer (2 cases of double primary colon cancer). Twelve cases were TNM staging II and 82 cases were stage III. Forty-six cases were well differentiated, 37 cases were moderately differentiated and 11 cases were poorly differentiated. Twenty-six patients (27.7%) with mismatch repair defects (dMMR) and microsatellite instability (MSI-H) were treated with immunotherapy alone, mainly programmed cell death protein-1 (PD-1); sixty-eight cases (72.3%) with mismatch repair proficient (pMMR) and microsatellite stability (MSS) were treated with immune combined with neoadjuvant therapy, mainly CapeOx (capecitabine+oxaliplatin) combined with PD-1 antibody plus long- or short-course radiotherapy, or PD-1 antibody combined with cytotoxic T lymphocyte associated antigen 4 (CTLA-4) antibody. Analysis and evaluation of adverse events during neoadjuvant immunotherapy were performed according to the National Cancer Institute Common Toxicity Standard version 3.0; the surgical complications were evaluated according to the Clavien-Dindo grading standard; the efficacy evaluation of neoadjuvant immunotherapy included the following indicators: major pathological remission (MPR) was defined as tumor regression induced by neoadjuvant therapy in pathology residual tumor ≤10%; pathological complete response (pCR) was defined as tumor regression induced by neoadjuvant therapy without residual tumor in pathology; the tumor response rate was disease control rate (DCR), namely the proportion of complete response (CR), partial response (PR) and stable disease (SD) in the whole group; the objective response rate (ORR) was CR+PR. Results: The median cycle of neoadjuvant immunotherapy was 4 (1-10) in whole group, and the incidence of immune-related adverse reactions was 37.2% (35/94), including 35 cases (37.2%) of skin-related adverse reactions, 21 cases (22.3%) of thyroid dysfunction and 8 cases (8.5%) of immune enteritis, of which grade III or above accounted for 1.1%. The median interval between completion of neoadjuvant therapy and surgery was 30 (21-55) days. There were 81 cases of radical resection of rectal cancer, 11 cases of radical resection of colon cancer, and 2 cases of colon cancer combined with other organ resection. The primary tumor resection of all the patients reached R0. The incidence of surgical-related complications was 22.3% (21/94), mainly anastomotic leakage (4 cases), pelvic infection (4 cases), abdominal effusion (3 cases), anastomotic stenosis (3 cases ) and abdominal and pelvic hemorrhage (2 cases). Grade I-II complications developed in 13 cases (13.8%), grade III and above complications developed in 8 cases (8.5%), no grade IV or above complications were found. During a median follow-up of 32 (1-46 ) months, DCR was 98.9% (93/94), ORR was 88.3 % (83/94), pCR was 41.5% (39/94), MPR was 60.6% (57/94). The pCR rate of 26 patients with dMMR and MSI-H undergoing simple immunotherapy was 57.7% (15/26), and MPR rate was 65.4% (17/26). The pCR rate of 68 pMMR and MSS patients undergoing combined immunotherapy was 35.3%(24/68), and MPR rate was 58.8% (40/68). Conclusions: Neoadjuvant immunotherapy has favorable tumor control rate and pathological remission rate for patients with initial resectable colorectal cancer. The incidences of perioperative adverse reactions and surgical complications are acceptable.
Colorectal Neoplasms/surgery* ; Female ; Humans ; Immunotherapy ; Male ; Middle Aged ; Neoadjuvant Therapy ; Rectal Neoplasms/surgery* ; Retrospective Studies

Starvation therapy is an emerging oncological treatment that targets the abnormally elevated nutrient uptake and metabolic pathways to inhibit and kill tumors. In addition to glucose, the targets of starvation therapy also include other nutrients in tumor cells.However, concerns like ineffective targeting and drug tolerance probably have an impact on their clinical translation.Nanomaterial-assisted starvation treatment has been developing quickly in recent years to address these concerns.In this review, several exemplary nanomedicines for starvation therapy and combined starvation therapy with other therapies were offered.They target nutrients other than glucose metabolism, including lactic acid, amino acids, and lipids, using nanomaterials to improve the efficacy of starvation therapy.This review provides reference for further development of nanomedicines with starvation treatment effect.

Objective: To investigate the impact of different levels of systolic blood pressure on all-cause, cardiovascular and cerebrovascular mortality in patients with nonvalvular atrial fibrillation (AF). Methods: This is a prospective cohort study. Patients with AF or atrial flutter diagnosed by 12 lead electrocardiogram during physical examination of Kailuan Group employees from July 2006 to December 2017 or previously diagnosed with AF in an inpatient setting at a level 2A hospital or above were eligible for the study. Baseline clinical characteristics including age, gender, systolic blood pressure were collected. According to the level of systolic blood pressure, patients were divided into systolic blood pressure<120 mmHg (1 mmHg=0.133 kPa)group, 120 mmHg ≤ systolic blood pressure<140 mmHg group, and systolic blood pressure ≥140 mmHg group. The time of first diagnosis with AF was defined as the start of follow-up and the final follow-up ended at December 2018. Primary endpoint was all-cause death. Related information was obtained through the social security system or inpatient medical records. The cause of death was defined according to the International Classification of Diseases disease (ICD-10) codes by professional medical stuffs. Multifactorial Cox proportional risk model was used to analyze the relative risk ratios for the occurrence of death in different systolic blood pressure level groups. The relationship between systolic blood pressure levels and mortality in the patients with AF was analyzed by using natural spline function curves. Results: A total of 1 721 patients with AF were enrolled (average age=(67.0±9.0) years), patients were followed up for (6.3±3.8) years. 544 out of 1 721 patients with AF died during the follow-up period (31.61%). The cumulative incidence rate of all-cause mortality, cardiovascular and cerebrovascular death was 26.13%, 25.59%, 36.96% and 14.86%, 11.87%, 19.76% respectively in the systolic blood pressure<120 mmHg, 120 mmHg ≤ systolic blood pressure<140 mmHg and systolic blood pressure ≥140 mmHg groups. The cumulative incidence rate of all-cause, cardiovascular and cerebrovascular death was significantly higher in the group with systolic blood pressure ≥140 mmHg than in 120 mmHg ≤ systolic blood pressure<140 mmHg group (P<0.05). Compared with 120 mmHg ≤ systolic blood pressure<140 mmHg group, multivariable Cox proportional hazards regression models showed that the HRs (95%CI) for all-cause, cardiovascular and cerebrovascular death were 1.47 (1.20 to 1.79) and 1.69 (1.27 to 2.26) for the group with systolic blood pressure ≥ 140 mmHg (P<0.05). In contrast, the HRs (95%CI) for all-cause, cardiovascular and cerebrovascular death in the systolic blood pressure<120 mmHg group were 0.99 (0.73-1.35) and 1.24 (0.82-1.89), respectively, with no statistically significant differences between the two groups (P>0.05). The natural spline curve showed that there was a "U" relationship between systolic blood pressure levels and all cause death and cardiovascular and cerebrovascular death in this patient cohort. Systolic blood pressure greater than or less than 123 mmHg was associated with increased risk of death of AF patients in this cohort. Conclusion: Compared with systolic blood pressure<120 mmHg and systolic blood pressure≥140 mmHg group, the risk of all-cause and cardiovascular and cerebrovascular death is the lowest in AF patients with 120 mmHg ≤ systolic blood pressure<140 mmHg in this cohort.

Objective:To understand the profile type of serum Epstein-Barr virus (EBV) antibodies in children with infectious mononucleosis (IM), and to analyze the significance of viral capsid antigen (VCA) IgG antibody affinity in the diagnosis of IM.Methods:Retrospective analysis was performed on the results of the serum anti-EBV antibody profile and plasma EBV nucleic acid test of 150 hospitalized children with IM diagnosed in Beijing Children′s Hospital, Capital Medical University, from May 2016 to May 2019.Anti-EBV antibody profiles, including anti-VCA-IgG, anti-VCA-IgM, anti-early antigen (EA) IgA, anti-EBV nuclear antigen (EBNA) IgG, and anti-VCA-IgG affinity, were detected by enzyme-linked immunosorbent assay (ELISA). Plasma EBV nucleic acids were detected by real-time quantitative PCR.Results:There were mainly two types of anti-EBV antibody profiles in 150 children with IM: (1)130 cases who were positive for anti-VCA-IgM/IgG, negative for anti-EBNA-IgG and positive for anti-VCA-IgG antibodies with low affinity, accounting for 86.7% (130/150 cases), of which 50 cases were positive for anti-early antigen IgA; (2)18 cases who were negative for anti-VCA-IgM, positive for anti-VCA-IgG, negative for anti-EBNA-IgG and positive for anti-VCA-IgG antibody with low affinity, accounting for 12.0% (18/150 cases), of which 5 cases were positive for anti-EA IgA.EBV DNA was measured in 132 children, with a posi-tive rate of 37.9% (50/132 cases).Conclusions:There were several types of serum EBV antibody profiles in children with IM, 12.0% of patients with IM in this study were negative for anti-VCA-IgM, and the diagnosis of IM was confirmed by the affinity of anti-VCA IgG.

Objective:To evaluate the performance of the Cepheid Xpert Xpress Flu/RSV assay (Xpert) in the detection of children infected with influenza virus (Flu) or respiratory syncytial virus (RSV).Methods:Nasopharyngeal specimens were collected from children who showed symptoms of respiratory infection and tested FluA, FluB and RSV by Xpert and sequencing assay respectively side by side. Discordant result were tested with a laboratory-developed real-time PCR for resolution.Results:A total of 388 nasopharyngeal swabs (NAPs) from children with acute respiratory tract infection were analyzed and the result showed 91.75-94.85% agreement between two tests. The sensitivity of FluA, FluB and RSV detected by Xpert and sequencing assay were 99.21% (125/126) vs. 92.86% (117/126), 100.00% (109/109) vs. 84.40% (92/109) and 100.00% (52/52) vs. 40.38% (21/52), respectively. The specificity of FluA, FluB and RSV detected by Xpert were all lower than that of the sequencing assay: 95.42% (250/262) vs 99.24% (260/262), 99.28% (277/279) vs 99.64% (278/279) and 99.70% (335/336) vs 100.00% (336/336). The positive predictive values (PPV) of FluA, FluB and RSV detected by Xpert were lower than those of the sequencing assay: 91.30% (126/138) vs. 98.33% (118/120), 98.18% (108/110) vs. 98.92% (92/93) and 98.11% (52/53) vs. 100.00% (21/21), respectively. The negative predictive values (NPV) of FluA, FluB and RSV detected by Xpert were higher than those of the sequencing assay: 99.60% (251/252) vs. 96.67% (261/270), 99.64% (279/280) vs. 94.27% (280/297) and 100.00% (337/337) vs. 91.60% (338/369).Conclusions:The Cepheid Xpert Xpress Flu/RSV assay is a sensitive, reliable and rapid assay for the detection of FluA, FluB and RSV in pediatrics.

The quality of Astragali Radix (AR) was closely related to the growth period. However, the current commodity grades of AR were only divided by diameter but not directly related to the growth period, which leads to the contradiction between the grade standard and the quality evaluation index. Therefore, solving this problem will be the key for the quality evaluation of AR. The present study established a potential quality evaluation approach for the absolute growth years' wild Astragali Radix (WAR) and transplanted Astragali Radix (TAR) based on the chemical components and anti-heart failure efficacy through adopting a bare-handed sections approach to rapidly identify the growth years of WAR. In this study, the absolute growth years of WAR were obtained by identifying the growth rings of 1-6 growth years root through the methods. The contents of flavonoids and saponins in 2-6 growth years' WAR were determined by HPLC-UV-ELSD. The contents of 12 chemical components and the anti-fatigue failure effects of WAR (4-year-old) and TAR were compared on rat models of heart failure induced by doxorubicin. Meanwhile, NMR-based untargeted metabolomics studies were performed to investigate the regulative effects of WAR and TAR. The result shows that the numbers of growth rings were consistent with the actual growth periods of AR. The HPLC-UV-ELSD determination indicated that the content of total flavonoids in WAR was significantly higher than that in TAR. Pharmacodynamics analysis revealed that the effects of WAR on cardiac function parameters (EF, FS and LVIDs), contents of serum CK and BNP were superior to those of TAR. 13 metabolites of heart were identified that had a higher rate of change in WAR group than TAR. Overall, a rapid identification method for the growth years of WAR was established, and the fact that WAR were significantly better than TAR in the heart failure rats was first proved in the paper. This study provided a scientific basis for establishing a novel commodity specification and grade of AR for clinical rational drug use.