Evaluation of Relationship of Pueraria lobata Quality from Different Producing Areas Based on "Climate Factor-component Content-antioxidant Capacity" / 中国实验方剂学杂志

ObjectiveThe correlation of Pueraria lobata producing areas， climate factors， total flavonoids of P. lobata， polysaccharide content of P. lobata， and antioxidant activity of P.lobata for medicinal application was analyzed， and the relationship between climate factors and the formation of P. lobata quality was evaluated. MethodThe scavenging rates of 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl（DPPH） and 2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)（ABTS） radicals by total flavonoids and polysaccharides of P. lobata were detected， and the correlation between the contents of each component and the information of producing areas and climate factors was analyzed. ResultThe ABTS+ scavenging rate by total flavonoids of P.lobata was negatively correlated with altitude （P<0.05） and positively correlated with annual sunshine hours （P<0.05）. The altitude was positively correlated with the total flavonoid content， while the annual sunshine hours were negatively correlated with the total flavonoid content. There was a negative correlation between total flavonoid content and ABTS+ scavenging rate by total flavonoids. In other words， lower altitude and longer annual sunshine hours indicated lower total flavonoid content and higher ABTS+ scavenging rate by total flavonoids. The ABTS+ scavenging rate by polysaccharides of P. lobata was negatively correlated with the frost-free period （P<0.05） and the mean temperature in July （P<0.01）. There was a positive correlation between the polysaccharide content of P. lobata and the frost-free period. The mean temperature in July was positively correlated with the polysaccharide content of P. lobata （P<0.05）. The polysaccharide content of P. lobata was negatively correlated with the ABTS+ scavenging rate by polysaccharides of P. lobata. In other words， a shorter frost-free period in the producing area and lower mean temperature in July indicated lower polysaccharide content of P. lobata and higher ABTS+ scavenging rate by polysaccharides of P. lobata. The mean temperature in July was significantly correlated with the contents of total flavonoids and polysaccharides in P. lobata samples （P<0.05）. The lower mean temperature in July was often accompanied by lower total flavonoid content of P. lobata， lower polysaccharide content of Pueraria lobata， and stronger antioxidant activity of P. lobata samples. ConclusionThe ability of P. lobata to remove ABTS+ is stronger than that of DPPH+. There is a significant correlation between climate factors， content， and antioxidant capacity in each producing area. Further research on the internal law of the formation of medicinal active components of P. lobata induced by core climate factors will provide a scientific basis for revealing the formation mechanism of genuine P. lobata and the subsequent control of P. lobata quality according to the environment of producing areas.

Comprehensive evaluation of Pinellia ternata germplasm resources based on phenotypic trait classification / 中国中药杂志

The evaluation of germplasm resources is the prerequisite for the development, utilization, and conservation of Chinese medicinal resources. The selection of excellent germplasm is the key to the breeding and orderly production of Pinellia ternata. In this study, 21 germplasm materials of P. ternata from major production areas in China were collected and analyzed for population diversity after phenotypic preliminary screening. The results have revealed that the P. ternata population has abundant phenotypic variation, and the phenotypic changes could be divided into five phenotypes in terms of organ trait variation. Further analysis of variation in 20 quantitative traits of the population revealed that the coefficient of variation for adenosine content(339.05%) was the largest, while the coefficient of variation for the underground plant height(16.35%) was the smallest. Correlation analysis showed that there was a strong correlation among various traits, with 52 pairs of traits showing highly significant correlation(P<0.01) and 19 pairs of traits showing a significant correlation(P<0.05). The 21 germplasms in the test could be classified into three major clusters by cluster analysis, with Cluster Ⅱ having the highest number and content of nucleosides, making it suitable for the selection and breeding of P. ternata varieties with high content of nucleosides. The yield in Cluster Ⅲ was higher than that in other groups, making it suitable for the selection and breeding of P. ternata varieties with a high yield. All trait indicators could be simplified into five principal component factors through principal component analysis, and the cumulative contribution rate was up to 86.04%. Further, comprehensive analysis using membership function and stepwise regression analysis identified nine traits, such as plant height, main leaf length, and underground plant height as characteristic indicators for the comprehensive evaluation of germplasm resources of P. ternata. BX007, BX008, and BX005 were identified as germplasms with both high yield and high uridine content, with BX007 having the highest uridine content of 479.51 μg·g~(-1). It belonged to the germplasm of P. ternata with double bulbils and could be cultivated as a potential good variety. Based on the phenotypic classification of P. ternata, systematic resource evaluation was carried out in this study, which could lay a foundation for the excavation of genetic resources and the breeding of new varieties of P. ternata.

Real-world Study of Medication Characteristics and Clinical Efficacy of Tenghuang Jiangu Tablets in Treatment of Knee Osteoarthritis in Remission Stage / 中国实验方剂学杂志

ObjectiveTo explore the medication characteristics and clinical efficacy of the Tenghuang Jiangu tablets in the treatment of knee osteoarthritis （KOA） in the remission stage in the real world，providing references for rational clinical use of this prescription. MethodBased on the "registration system of KOA treated with Tenghuang Jiangu tablets"，2 439 KOA cases in the remission stage were analyzed by SPSS 25.0，IBM SPSS Modeler18.0，and Apriori algorithm. To be specific，the age，body mass index （BMI），and course of treatment were described in the form of x̄±s. The information on gender，K-L grade，daily dose，and frequency of drug use was described by frequency analysis. The number of cases，course of treatment，daily dose，and drug use frequency of the single-use group and the combined-use group were described by frequency analysis，and the combination of drugs was described by frequency analysis and Apriori algorithm. Mann-Whitney U test was employed to compare the scores of Visual Analogue Scale （VAS），Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC），pain，stiffness，and joint function between the single-use group and the combined-use group. ResultThe results of clinical treatment showed that 2 439 patients with KOA in the remission stage were treated with Tenghuang Jiangu tablets，with 1 432 （58.71%） in the single-use group and 1 007 （41.29%） in the combined-use group. The average daily dose of Tenghuang Jiangu tablets was （3.90±1.44） g，and the majority of the patients were at grade Ⅱ （54.47%）. The daily average daily dose of Tenghuang Jiangu tablets in the single-use group was （3.64±1.35） g，which was lower than that in the combined-use group ［（4.26±1.48） g，P<0.05］. In the combined use，the top three western medicines were glucosamine （270 times，14.68%），sodium hyaluronate （126 times，6.85%），and imrecoxib （116 times，6.31%），and the top three Chinese medicines were Huoxuezhitong capsules/tablets/ointments （31 times，1.69%），Biqi capsules （25 times，1.36%），and Maizhiling （23 times，1.25%）. As for the overall clinical efficacy，the VAS score was （5.13±0.93） score before treatment and （2.22±1.18） score after treatment （P<0.05），with an overall average decrease of （2.91±1.14） score， and the average decrease in the single-use group was （2.76±1.43） score， which was lower than that in the combined-use group ［（3.12±1.36） score，（P<0.01）］. The WOMAC score was （31.05±11.84） score before treatment and （13.55±9.91） score after treatment （P<0.05）. The overall average decrease was （17.50±11.79） score， and the average decrease in the single-use group and combined-use group was （16.39±11.14） score and （19.08±12.50） score，respectively （P<0.01）. The patients with KOA>grade Ⅱ accounted for 91.34%（1 308/1 432） and 93.55%（942/1 007） in the single-use group and combined-use group，respectively （χ2=80.026，P<0.05）. A total of 43.37%（621/1 432） of the patients in the single-use group had other complications，lower than that in the combined-use group ［54.92%（553/1 432），（χ2=20.087，P<0.01）］. ConclusionMore than half of the patients with KOA in the remission stage are treated with Tenghuang Jiangu tablets alone，and the combination therapy is mainly applied in patients with severe conditions or other complications. In relieving knee joint pain and improving joint stiffness and joint function，both the Tenghuang Jiangu tablets alone and the combination therapy are effective.

Meta-analysis of Effect of Tripterygium wilfordii Polyglycoside Tablets Combined with Methotrexate and/or Leflunomide on Autoantibodies in Rheumatoid Arthritis / 中国实验方剂学杂志

ObjectiveTo evaluate the effect of Tripterygium wilfordii polyglycoside tablets （TWPT） combined with conventional synthetic disease-modifying antirheumatic drugs （csDMARDs） including methotrexate （MTX） and/or leflunomide （LEF） on autoantibodies in rheumatoid arthritis （RA） patients. MethodPubMed， EMBASE， Web of Science， Cochrane Library， China National Knowledge Infrastructure （CNKI）， VIP， Wanfang Data， and China Biomedical Literature Service System （SinoMed） were searched for randomized controlled trials （RCTs） of TWPT combined with MTX and/or LEF in the treatment of RA patients from database inception to December 1， 2021. Primary outcome indicators included rheumatoid factor （RF） and anti-citrullinated protein antibody （ACPA）， and secondary outcome indicators included immunoglobulin （IgA， IgG， and IgM） and adverse drug events （ADE）. ResultThirty-one RCTs， involving 2 643 adult patients， were included， including 20 RCTs of TWPT combined with MTX， 10 of TWPT combined with LEF， and one of TWPT combined with MTX and TWPT. The follow-up time ranged from two weeks to 13 months. Compared with csDMARDs alone， TWPT combined with other drugs significantly improved serum RF of RA patients ［SMD=-2.45， 95% CI ［-2.97， -1.93］， P<0.000 01］， anti-CCP ［SMD=-1.41， 95% CI （-2.35， -0.48）， P=0.003］， IgM ［SMD=-1.90， 95% CI （-3.03， -0.76）， P=0.001］， and IgA ［SMD=-1.18， 95% CI （-2.23， -0.12）， P=0.03］. There were no significant effects on IgG ［SMD=-1.02， 95% CI （-2.04， 0.01）， P=0.05］ and ADE ［RR=0.87， 95% CI （0.66， 1.15）， P=0.32］. ConclusionThe results of this study show that compared with csDMARDs alone， TWPT combined with csDMARDs can effectively improve the levels of autoantibodies in RA patients without increasing the incidence of ADE. However， due to the limited quality and quantity of the included RCTs， the relevant conclusions are only used as a reference for the clinical diagnosis and treatment of RA， and more high-quality studies are still needed to further confirm their efficacy.

Contamination of common food-borne pathogens in foods sold in Changzhou / 公共卫生与预防医学

Objective To understand the contamination status of common food-borne pathogens in foods sold in Changzhou, and to provide evidence for food safety risk assessment and prevention of food-borne diseases. Methods From 2010 to 2020 , 2 513 samples of 17 types of foods were collected in Changzhou area. The detection of pathogenic bacteria was carried out in accordance with the standard operation procedure specified in the “Workbook for Surveillance on Food Microorganisms and Pathogenic Factors in Jiangsu Province”. Results A total of 260 positive samples of common food-borne pathogens were detected in all 2 513 samples with an overall detection rate of 10.30%. Single factor analysis showed that the detection rate of pathogenic bacteria in non-ready-to-eat samples was higher than that in ready-to-eat samples (χ2=148.875，P =0.000). The detection rate of pathogenic bacteria in bulk samples was higher than that in prepackaged ones (χ2=70.956，P=0.000). There is a difference in the detection rate of food-borne pathogens from different types of sampling sites (χ2=65.017，P=0.000). Logistic regression analysis showed that ready-to-eat food, packaging type, and sampling season were significantly correlated with the detection rate of food-borne pathogens. The detection rate of pathogenic bacteria in samples collected in the third or fourth quarters was higher than that in the first quarter. Conclusion The commercial foods sold in Changzhou have a relatively high level of contamination of food-borne pathogenic bacteria, and they should be fully heated and sterilized before consumption. The relevant departments should strengthen supervision and health education in summer and autumn.

Traditional Chinese medicine microbiomics and its research strategies / 中国中药杂志

The tight relationships between microbiome and traditional Chinese medicine(TCM)have been widely recognized. New technologies, results, and theories are emerging in the field of microbiomics in recent years with the advances in high-throughput sequencing and multi-omics technologies. Based on the previous research, the present study has proposed the concept of TCM microbiomics(TCMM), which is an interdisciplinary subject aiming at elucidating the functions and applications of microbiome in the areas of herb resources, herb processing, herb storage, and clinical effects by using modern technology of biology, ecology, and informatics. This subject essentially contains the structures, functions, interactions, molecular mechanisms, and application strategies of the microbiome associated with the quality, safety, and efficacy of TCM. Firstly, the development of the TCMM concept was summarized, with the profound understanding of TCMM on the complexity and entirety of microbiome being emphasized. Then, the research contents and applications of TCMM in promoting the sustainable development of herb resources, improving the standardization and diversification of herb fermentation, strengthening the safety of herb storage, and resolving the scientific connotation of theories and clinical efficacy of TCM are reviewed. Finally, the research strategies and methods of TCM microbiomics were elaborated from basic research, application research, and system research. TCMM is expected to promote the integrative development of TCM with frontier science and technology, thereby expanding the depth and scope of TCM study and facilitating TCM modernization.

Hepatotoxicity and mechanism of Rhododendri Mollis Flos based on zebrafish model / 中国中药杂志

This study used the zebrafish model to explore the hepatotoxicity of Rhododendri Mollis Flos(RMF). The mortality was calculated according to the number of the survival of zebrafish larvae 4 days after fertilization under different concentration of RMF, and the dose-toxicity curve was fitted to preliminarily evaluate the toxicity of RMF. The liver phenotypes under the sublethal concentration of RMF in the treatment group and the blank control group were observed by hematoxylin-eosin(HE) staining and acridine orange(AO) staining. Meanwhile, the activities of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were determined to confirm the hepatotoxicity of RMF. Real-time quantitative polymerase chain reaction(real-time PCR) and Western blot were used to determine the expressions of genes and proteins in zebrafish larvae. Gas chromatography time-of-flight mass spectrometry(GC-TOF-MS) was used to conduct untargeted metabolomics testing to explore the mechanism. The results showed that the toxicity of RMF to zebrafish larvae was dose-dependent, with 1 100 μg·mL~(-1) of the absolute lethal concentration and 448 μg·mL~(-1) of sublethal concentration. The hepatocyte apoptosis and degeneration appeared in the zebrafish larvae under the sublethal concentration of RMF. The content of ALT and AST in zebrafish larvae at the end of the experiment was significantly increased in a dose-dependent manner. Under the sublethal concentration, the expressions of genes and proteins related to apoptosis in zebrafish larvae were significantly increased as compared with the blank control group. The results of untargeted metabolomics showed that the important metabolites related to the he-patotoxicity of RMF were mainly enriched in alanine, aspartic acid, glutamic acid, and other pathways. In conclusion, it is inferred that RMF has certain hepatotoxicity to zebrafish larvae, and its mechanism may be related to apoptosis.

Development of flow cytometry and its application in plant research / 生物工程学报

Flow cytometry is a multi-parameter, rapid and efficient method for qualitative analysis and quantitative determination of various fluorescently labeled particles in liquid flow. Flow cytometry has been applied in multiple disciplines such as immunology, virology, molecular biology, cancer biology and infectious disease monitoring. However, the application of flow cytometry in plant research is hampered due to the special composition and structure of plant tissues and cells, such as cell walls and secondary metabolites. In this paper, the development, composition and classification of flow cytometry were introduced. Subsequently, the application, research progress and application limitations of flow cytometry in plant field were discussed. At last, the development trend of flow cytometry in plant research was prospected, which provides new perspectives for broadening the potential application scope of plant flow cytometry.

The common morphology and clinical significance of the axillary arch / 中华外科杂志

Axillary arch is the most common type of axillary muscle fiber variation, with about 10.8% incidence in the Chinese population. Its natural forms are varied and fluid, with different starting points and terminations, and clinicians frequently lack recognition. Under commonly applicated sentinel lymph node biopsy, the axillary arch has been endowed with more clinical significance. The fabric of axillary arch will not only block lymphatic drainage in axilla and unclear anatomical level of axillary dissection, but also compress the axillary neurovascular bundle, causing upper limb venous thrombosis, lymphedema and nerve entrapment. The intumescent axillary arch may also show abnormal axillary bulge. In addition to finding axillary arch during cadaveric study and operation, several of imaging methods availably diagnose axillary arch preoperative, which can create new way for detection of axillary arch and extension of the surgical plan of sentinel lymph node biopsy. Although embryology and comparative anatomy have been used to explain the origin of the axillary arch, most of the ideas are still hypotheses and need further study.

Prevalence and incidence of heart failure among community in China during a three-year follow-up / 老年心脏病学杂志（英文版）

BACKGROUND@#Epidemiological surveys on heart failure (HF) in Chinese community are relatively lacking. This study aimed to estimate the prevalence and incidence of HF among community residents in southern China.@*METHODS@#Baseline data of this prospective study was collected from 2015 to 2017 among 12,013 permanent residents aged ≥ 35 years in Guangzhou, China. The same survey process was carried out for individuals aged ≥ 65 years after a three-year follow-up.@*RESULTS@#The overall prevalence of HF in community residents aged ≥ 35 years was 1.06%. Male had significantly higher risk of HF prevalence [odds ratio (OR) = 1.50, P = 0.027]. The gender-adjusted risk of HF was 1.48 times higher per 10 years aging. HF prevalence was statistically associated with atrial fibrillation, valvular heart disease, hypertension and chronic obstructive pulmonary disease after adjusting for age and gender (OR = 8.30, 5.17, 1.11, 2.28, respectively; all P < 0.05). HF incidence in individuals aged ≥ 65 years were 847 per 100,000 person-years. Baseline atrial fibrillation, valvular heart disease, and diabetes mellitus were risk factors for HF incidence for individuals aged ≥ 65 years adjusting for age and gender (OR = 5.05, 3.99, 2.11, respectively; all P < 0.05). Besides, residents with new-onset atrial fibrillation and myocardial infarction were at significantly higher risk of progression to HF (OR = 14.41, 8.54, respectively; all P < 0.05).@*CONCLUSIONS@#Both pre-existing and new-onset cardiovascular diseases were associated with HF incidence in southern China. Management of related cardiovascular diseases may be helpful to reduce the incidence of HF.

Assay of amino acids in leaves of Eucommia ulmoides under arbor forest mode and leaf-oriented cultivation mode by pre-column derivatization HPLC / 中国中药杂志

This study aims to develop the pre-column derivatization high performance liquid chromatography(HPLC) method for the determination of 16 kinds of amino acids in Eucommia ulmoides leaves, and compare the content of amino acids in the leaves harvested at different time and under leaf-oriented cultivation mode(LCM) and arbor forest mode(AFM). The HPLC conditions are as below: phenyl isothiocyanate(PITC) as pre-column derivatization agent, Agilent ZORBAX C_(18 )column(4.6 mm×250 mm, 5 μm), mobile phase A of acetonitrile-water(80∶20), mobile phase B of 0.1 mol·L~(-1) sodium acetate solution-acetonitrile(94∶6), gradient elution, flow rate of 1.0 mL·min~(-1), injection volume of 5 μL, column temperature of 40 ℃, and detection wavelength of 254 nm. The HPLC profile indicated well separation of 16 kinds of amino acids and the amino acid content in E. ulmoides leaves was up to 16.26%. In addition, the amino acid content in leaves of E. ulmoides under LCM was higher than under AFM. The amino acid content varied with the harvesting time. Through orthogonal partial least squares discriminant analysis, the amino acids of E. ulmoides under LCM and AFM were compared, which can distinguish the leaves under LCM from those under AFM. Principal component analysis was applied to comprehensively score the amino acids of E. ulmoides leaves. The results showed that the score of leaves under LCM was higher than that under AFM. Nutritional evaluation results indicated that the proteins in E. ulmoides leaves belonged to high-quality vegetable proteins. The established method for the determination of amino acid content is reliable. With the amino acid content as index, the leaf quality of E. ulmoides under LCM is better than that under AFM. This study lays a theoretical basis for the promotion of LCM for E. ulmoides and the development of medicinal and edible products from E. ulmoides leaves.

A Core Genome Multilocus Sequence Typing Scheme for Proteus mirabilis / 生物医学与环境科学（英文）

OBJECTIVE@#A core genome multilocus sequence typing (cgMLST) scheme to genotype and identify potential risk clonal groups (CGs) in Proteus mirabilis.@*METHODS@#In this work, we propose a publicly available cgMLST scheme for P. mirabilis using chewBBACA. In total 72 complete P. mirabilis genomes, representing the diversity of this species, were used to set up a cgMLST scheme targeting 1,842 genes, 635 unfinished (contig, chromosome, and scaffold) genomes were used for its validation.@*RESULTS@#We identified a total of 205 CGs from 695 P. mirabilis strains with regional distribution characteristics. Of these, 159 unique CGs were distributed in 16 countries. CG20 and CG3 carried large numbers of shared and unique antibiotic resistance genes. Nine virulence genes ( papC, papD, papE, papF, papG, papH, papI, papJ, and papK) related to the P fimbrial operon that cause severe urinary tract infections were only found in CG20. These CGs require attention due to potential risks.@*CONCLUSION@#This research innovatively performs high-resolution molecular typing of P. mirabilis using whole-genome sequencing technology combined with a bioinformatics pipeline (chewBBACA). We found that the CGs of P. mirabilis showed regional distribution differences. We expect that our research will contribute to the establishment of cgMLST for P. mirabilis.

Comparison of pingyangmycin fibrin glue composite and pingyangmycin dexamethasone composite in the treatment of pharyngolaryngeal venous malformation / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze and compare the efficacy and safety of pingyangmycin fibrin glue composite (PFG) and pingyangmycin dexamethasone composite (PD) in the treatment of pharyngolaryngeal venous malformation (VM). Methods: The clinical data of 98 patients with pharyngolaryngeal VM who underwent sclerotherapy with pingyangmycin composite in the First Affiliated Hospital of Sun Yat-sen University from June 2013 to November 2022 were retrospectively analyzed. According to their treatment, patients were divided into PFG group (n=34) and PD group (n=64), among those patients there were 54 males and 44 females, aged 1-77(37.06±18.86)years. The lesion size, total treatment times and adverse events were recorded before and after treatment. And the efficacy was divided into three grades: recovery, effective and invalid. According to the length of VM, all patients were divided into three subgroups, to compare the differences in efficacy and treatment times between each two groups.And finally the adverse events and their treatments were analyzed. SPSS 25.0 software was used for statistical analysis. Results: The efficacy of PFG group was 94.11%(32/34), the recovery rate was 85.29%(29/34).And the efficacy of PD group was 93.75%(60/64), the recovery rate was 64.06%(41/64). No serious adverse eventst occurred in subgroup comparison, there was no statistical difference between the two groups in efficacy and the times of treatments when the length was≤3 cm (Zefficacy=1.04, ttreatment times=2.18, P>0.05); when the length was 3-5 cm, there was no significant efficacy difference between the two groups(Zefficacy=1.17, P>0.05), but the treatment times of PFG were less (ttreatment times=4.87, P<0.01); when the length≥5 cm, efficacy of PFG was significantly better than PD (Zefficacy=2.94, P<0.01), and had fewer treatments times (ttreatment times=2.16, P<0.01). There were no serious adverse events in either group during treatment and follow-up. Conclusion: Both PFG and PD are safe and effective composite sclerotherapy agent for the treatment of laryngeal VM, but PFG has a higher cure rate and fewer treatment times for massive lesions.

Analysis of clinicopathological characteristics, therapeutic strategy and prognosis of 501 patients with gastric neuroendocrine neoplasms attending a single center / 中华胃肠外科杂志

Objective: To explore the clinicopathological features, treatment strategy and to analysis of prognosis-related risk factors of gastric neuroendocrine neoplasms(G-NEN). Methods: In this study, a retrospective observational study method was used to collect the clinicopathological data of patients diagnosed with G-NEN by pathological examination in the First Medical Center of PLA General Hospital from January 2000 to December 2021. The basic information of the patients, tumor pathological characteristics, and treatment methods were entered, and the treatment information and survival data after discharge were followed up and recorded. The Kaplan-Meier method was used to construct survival curves, and the log-rank test to analyze the differences in survival between groups. Cox Regression model analysis of risk factors affecting the prognosis of G-NEN patients. Results: Among the 501 cases confirmed as G-NEN, 355 were male and 146 were female, and their median age was 59 years. The cohort comprised 130 patients (25.9%) of neuroendocrine tumor (NET) G1, 54 (10.8%) of NET G2, 225 (42.9%) of neuroendocrine carcinoma (NEC), and 102 cases (20.4%) of mixed neuroendocrine-non-neuroendocrine(MiNEN). Patients NET G1 and NET G2 were mainly treated by endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR). The main treatment for patients with NEC/MiNEN was the same as that for gastric malignancies, namely radical gastrectomy+lymph node dissection supplemented with postoperative chemotherapy. There were significant differences in sex, age, maximum tumor diameter, tumor morphology, tumor numbers, tumor location, depth of invasion, lymph node metastasis, distant metastasis, TNM staging and expression of immunohistological markers Syn and CgA among NET, NEC, and MiNEN patients (all P<0.05). Further for NET subgroup analysis, there were significant differences between NET G1 and NET G2 in the maximum tumor diameter, tumor shape and depth of invasion(all P<0.05). 490 patients (490/501, 97.8%) were followed up with a median of 31.2 months. 163 patients had a death during follow-up (NET G1 2, NET G2 1, NEC 114, MiNEN 46). For NET G1, NET G2, NEC and MiNEN patients,the 1-year overall survival rates were 100%, 100%, 80.1% and 86.2%, respectively; the 3-year survival rates were 98.9%, 100%, 43.5% and 55.1%, respectively. The differences were statistically significant (P<0.001). Univariate analysis showed that gender, age, smoking history, alcohol history, tumor pathological grade, tumor morphology, tumor location, tumor size, lymph node metastasis, distant metastasis, and TNM stage were associated with the prognosis of G-NEN patients (all P<0.05). Multivariate analysis showed that age ≥60 years, pathological grade of NEC and MiNEN, distant metastasis, and TNM stage III-IV were independent factors influencing the survival of G-NEN patients (all P<0.05). 63 cases were stage IV at initial diagnosis. 32 of these were treated with surgery and 31 with palliative chemotherapy. Stage IV subgroup analysis showed that the 1-year survival rates were 68.1% and 46.2% in the surgical treatment and palliative chemotherapy groups, respectively, and the 3-year survival rates were 20.9% and 10.3%, respectively; the differences were statistically significant (P=0.016). Conclusions: G-NEN is a heterogeneous group of tumors. Different pathological grades of G-NEN have different clinicopathological features and prognosis. Factors such as age ≥ 60 years old, pathological grade of NEC/MiNEN, distant metastasis, stage III, IV mostly indicate poor prognosis of patients. Therefore, we should improve the ability of early diagnosis and treatment, and pay more attention to patients with advanced age and NEC/MiNEN. Although this study concluded that surgery improves the prognosis of advanced patients more than palliative chemotherapy, the value of surgical treatment for patients with stage IV G-NEN remains controversial.

A case of stage Ⅲ pneumoconiosis with large shadow by burr-like changes misdiagnosed as lung cancer / 中华劳动卫生职业病杂志

Pneumoconiosis is characterized by chronic lung inflammation and fibrosis, and inflammation can promote pulmonary fibrosis, which in turn leads to pneumoconiosis. When a large shadow with a long diameter of not less than 2 cm and a short diameter of not less than 1 cm appears in the lung, it can be classified as stage Ⅲ pneumoconiosis. This paper reports a case of stage Ⅲ pneumoconiosis with a large shadow in the upper right lung accompanied by burr-like changes misdiagnosed as lung cancer by CT examination.When the large shadow lesions in patients with pneumoconiosis and lung cancer are difficult to distinguish on CT, an additional MRI examination, particularly T(2)W imaging sequence is useful sequence for identifying the two.

Value of detection of peripheral blood miR-194 combined with fecal miR-143 in the clinical screening of colorectal cancer / 国际肿瘤学杂志

Objective:To explore and analyze the value of detection of peripheral blood miR-194 combined with fecal miR-143 in the clinical screening of colorectal cancer.Methods:A total of 83 patients diagnosed with colorectal cancer by pathological tissue admitted to Huangshi Hospital of Traditional Chinese Medicine of Hubei Province from October 2019 to October 2020 were selected as the observation group, and 50 healthy volunteers who underwent physical examinations during the same period were selected as the control group. The levels of miR-194 in peripheral blood and miR-143 in feces were detected by fluorescence quantitative PCR. The level difference between the two groups and their correlations with clinicopathological parameters of patients with colorectal cancer were analyzed. Receiver operating characteristic (ROC) curve was drawn based on peripheral blood miR-194 and fecal miR-143 to evaluate their value for clinical screening of colorectal cancer.Results:The level of miR-194 in peripheral blood of the observation group was significantly higher than that of the control group (1.91±0.34 vs. 0.76±0.23) , while the level of fecal miR-143 in the observation group being significantly lower than that of the control group (1.85±0.43 vs. 2.48±0.62) , with statistically significant differences ( t=21.16, P<0.001; t=6.91, P<0.001) . Age of patients with colorectal cancer ( t=0.83, P=0.408; t=1.17, P=0.244) , TNM stage ( t=1.03, P=0.307; t=0.11, P=0.909) , lymphatic metastasis ( t=0.37, P=0.711; t=1.85, P=0.068) , distant metastasis ( t=0.41, P=0.683; t=1.72, P=0.089) were not correlated with the levels of peripheral blood miR-194 and fecal miR-143. When the cut-off value of miR-194 in peripheral blood was 1.82, the area under the ROC curve for the diagnosis of colorectal cancer was 0.76, and the diagnostic sensitivity and specificity were 79.38% and 74.29%, respectively. When the cut-off value of fecal miR-143 was 2.16, the area under the ROC curve for the diagnosis of colorectal cancer was 0.71. At this time, the diagnostic sensitivity and specificity were 76.54% and 73.61%, respectively. The area under ROC curve of combined detection for colorectal cancer was 0.81, and the diagnostic sensitivity and specificity were 83.46% and 75.43%, respectively. Conclusion:Peripheral blood miR-194 is highly expressed in colorectal cancer patients, and fecal miR-143 is low in colorectal cancer patients. The combined detection of the two has a high sensitivity for early diagnosis of colorectal cancer, which can provide important reference basis for early diagnosis of colorectal cancer and has high clinical application value.

Exploration of risk factors and establishment of nomograms model for postoperative adjuvant chemotherapy in stage Ⅰ gastric cancer / 国际外科学杂志

Objective:To identify the risk factors associated with postoperative adjuvant chemotherapy in patients with stage I gastric cancer and establish nomograms model based on risk factors.Methods:In this retrospective case-control study, 161 cases with stage Ⅰ primary gastric adenocarcinoma were included who underwent gastrectomy at the Department of General Surgery of the First Medical Center of Chinese PLA General Hospital from January to December in 2020, including 129 male cases and 32 females cases, with the average age of (59.90±0.80) years. Among them, 41 cases were treated with postoperative adjuvant chemotherapy (chemotherapy group), while 120 cases who did not receive postoperative adjuvant chemotherapy (no chemotherapy group). Univariate and multivariate Logistic regression analyses were used to identify the risk factors of adjuvant chemotherapy in stage Ⅰ gastric cancer patients and establish the nomograms predictive model. ROC curve and calibration curve were used to evaluate the performance of the model.Results:Multivariate analysis revealed that primary tumor site, tumor size, T stage, N stage lymph-vascular tumor embolus or perineural invasion were the independent risk factors of postoperative adjuvant chemotherapy for stage Ⅰ gastric cancer( P<0.05). The ROC curve indicated that area under the curve (AUC) of the multivariate model was 0.91(95% CI: 0.86-0.97). The calibration curve showed that probability predicted by nomograms was consistent with the actual situation(C-index: 0.91). Conclusions:The tumor located in the proximal stomach, tumor size>2 cm, T 2, N 1, lymph-vascular tumor embolus or perineural invasion maybe be the risk factors for chemotherapy decision in stage Ⅰ gastric cancer patients. The established model has good predictive ability for postoperative chemotherapy of stage Ⅰ gastric cancer patients, which might provide reference for the selection of clinical decisions in this part of patients.

Application and challenge of neoadjuvant immunotherapy on perioperative treatment for locally advanced gastric cancer / 国际外科学杂志

The application of immunotherapy in advanced gastric cancer has become a research hotspot. At the same time, the combination of immunotherapy and neoadjuvant therapy is expected to further achieve tumor downstage, pathological remission, increase the proportion of R0 resection, which enhance the overall therapeutic effect of locally advanced gastric cancer (LAGC). Whether neoadjuvant immunotherapy affects perioperative complications, adverse events, tumor pathological responses, and long-term survival in LAGC is still in the initial stage of clinical exploration, which depends on large-scale prospective phase III clinical studies to demonstrate its clinical value. Meanwhile, the application of new innovative drugs and comprehensive perioperative treatment, screening high-specific biomarkers for therapeutic prediction, and weighing the selection of neoadjuvant cycle and interval of treatment-operation time are helpful to optimize and standardize the rational application of neoadjuvant immunotherapy, and ultimately bring benefits to patients.

Expressions of programmed death 1 and its ligand in acute myeloid leukemia patients and their effect on anti-tumor effect of programmed death receptor 1-positive natural killer cells in vitro / 白血病·淋巴瘤

Objective:To investigate the expression of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway in patients with acute myeloid leukemia (AML) and its relationship with clinical features and prognosis, and to examine its effect on PD-1-positive natural killer (NK) cells against AML cells in vitro.Methods:The bone marrow samples of 65 AML patients and the peripheral blood of 32 AML patients diagnosed in Affiliated Cancer Hospital of Zhengzhou University from July 2019 to December 2020 were prospectively collected, and the peripheral blood of 24 healthy people was taken as healthy control. The expression level of PD-L1 in bone marrow tumor cells and expression level of PD-1 in peripheral blood NK cells were detected by flow cytometry. The correlations of PD-1 expression in bone marrow tumor cells and PD-1 expression in NK cells with the clinicopathological features, curative effect and prognosis of patients were analyzed. Flow cytometry was used to detect the expression level of PD-L1 in AML cell line THP-1 (target cells) and the expression level of PD-L1 in NK cell line NKL (effector cells). THP-1 cells treated with and without 25 μmol/L of PD-L1 inhibitor fraxinellone were used as experimental group and control group, and co-cultured with NKL cells at different effector-to-target ratios. The apoptosis of THP-1 cells and the expression of NKG2D in NKL cells were detected by flow cytometry, the cell proliferation status was detected by CCK-8 and the cell proliferation inhibition rate was calculated; the levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in the supernatant of co-culture system were detected by enzyme-linked immunosorbent assay (ELISA).Results:The proportion of AML patients with PD-L1-positive expression in bone marrow tumor cells was higher than that in the healthy control group [38.5% (25/65) vs. 8.3% (2/24), P = 0.029]. The proportion of AML patients with PD-1-positive expression in peripheral blood NK cells was higher than that in the healthy control group [40.6% (13/32) vs. 12.5% (3/24), P = 0.035]. There were no statistical differences in sex, age, hemogram, proportion of primordial cells, risk stratification, chromosomal karyotype, gene mutation (except NPM1 gene), fusion gene and French-American-British cooperative group (FAB) typing between patients with PD-L1 positive and negative in bone marrow tumor cells and between patients with PD-1 positive and negative in peripheral blood NK cells (all P > 0.05). In relapsed/refractory patients, the proportion of patients with PD-L1-positive expression in bone marrow tumor cells was higher than that in newly treated patients [58.8% (10/17) vs. 31.2% (15/48), P = 0.045]. There was no significant difference in the proportion of patients with PD-1-positive expression in peripheral blood NK cells between relapsed/refractory patients and newly treated patients [(38.5% (5/13) vs. 42.1% (8/19), P = 0.837]. There was no statistical difference in complete remission (CR) rate between PD-L1 positive and negative patients [69.6% (16/23) vs. 74.3% (26/35), P > 0.05]. There was no statistical difference in CR rate between PD-1 positive and negative patients [66.7% (8/12) vs. 70.6% (12/17), P > 0.05]. There was no statistical difference in recurrence rate after CR between PD-L1 positive and negative patients [12.5% (2/16) vs. 19.2% (5/26), P > 0.05]. There was no statistical difference in recurrence rate after CR between PD-1 positive and negative patients [25.0% (2/8) vs. 16.7% (2/12), P > 0.05]. Flow cytometry showed that the positive rate of PD-1 in NKL cells was (67±6)% and the positive rate of PD-L1 in THP-1 cells was (85±5)%. After co-culture with NKL cells, the apoptotic rate and proliferation inhibition rate of THP-1 cells were higher in the experimental group compared with the control group, the expression of NKG2D on the surface of NKL cells was elevated, and the levels of IFN-γ and TNF-α in the co-culture supernatant were increased. Conclusions:In AML patients, the expression of PD-L1 in bone marrow tumor cells is high, and the expression of PD-1 in peripheral blood NK cells is also high. The expression of PD-L1 in bone marrow tumor cells of relapsed/refractory AML patients is higher than that of newly treated patients. Inhibition of PD-L1 expression in THP-1 cells can enhance the tumor killing activity of NKL cells in vitro. The mechanism may be that inhibition of PD-L1 expression in THP-1 cells up-regulates the expression of NKL cell activated receptor NKG2D and promotes the secretion of IFN- γ and TNF- α.

Progress of small molecule targeted therapy for acute myeloid leukemia / 白血病·淋巴瘤

Acute myeloid leukemia (AML) is the most common subtype of acute leukemia in adults with significant heterogeneity. Among hematological malignancies, targeted therapy for AML comes relatively late. Although traditional chemotherapy is still an indispensable part of AML treatment, more and more small molecule targeted drugs have been used in recent years since 2017. This article reviews the progress of small molecule targeted drugs for AML at the 64th American Society of Hematology annual meeting.