Gastric cancer(GC)is one of the most common tumors and the fourth leading cause of cancer-related death worldwide.Due to the lack of specific signs in early GC,most cases are diagnosed at an advanced stage,often accompanied by infiltration and distant metastasis.Although chemotherapy is the most commonly used treatment for gastric cancer,due to the emergence of drug resistance,many patients will still relapse after chemo-therapy,resulting in poor prognosis.Exosome(EXOs)in the Tumor micro environment(TME)can participate in intercellular communication and play an important role in GC distant metastasis and drug resistance.At present,the detailed mechanism of GC distant metastasis and drug resistance is still unclear.Identifying the exosome-induced mechanism involved in GC distant metastasis and drug resistance can help us find more reliable treatment methods for GC metastasis and drug resistance.This article reviews the mechanism of exosome in GC distant metastasis and drug resistance,in order to provide help for the diagnosis,treatment and research of GC.

Objective To investigate the effect and mechanism of Houpu Sanwu decoction on subcutaneous tumors in C57BL/6J mice.Methods Mouse colorectal cancer MC-38 cells were injected subcutaneously into C57BL/6J mice to establish a subcutaneous tumor model of colorectal cancer.The model mice were then divided randomly into model control,Houpu Sanwu decoction(HPSWD)low dose,HPSWD medium dose,HPSWD high dose,5-fluorouracil(5-FU),and combination groups(5-FU+HPSWD medium dose)(n=6 mice per group).The mice were treated with normal saline and Houpu Sanwu decoction by gavage,or normal saline and 5-FU by intraperitoneal injection once a day for 24 consecutive days.During the intervention period,the mental state,diet,and other general conditions of the mice,as well as changes in tumor volume,were monitored regularly.At the end of the experiment,the subcutaneous tumors in each group were removed and weighed,and pathological features were examined by hematoxylin and eosin staining.Transmission electron microscopy,Western blot,and nanoparticle tracking analysis were used to identify exosomes derived from colorectal cancer tissues.Tumor mRNA and protein expression levels of Rab27a and the exosome markers CD63,TSG101,and ALIX were detected by reverse transcription-quantitative polymerase chain reaction and Western blot,respectively.Results Houpu Sanwu decoction inhibited tumor growth in mice.Tumor growth was inhibited to varying degrees in all the HPSWD dose groups and in the combination group.The HPSWD medium does group showed the greatest anticancer effect,and the combination group showed a synergistic effect with 5-FU.Houpu Sanwu decoction induced tumor necrosis in a dose-dependent manner,with a similar anticancer effect to 5-FU.Houpu Sanwu decoction also inhibited the protein and mRNA expression levels of Rab27a and the exosome-specific markers CD63,ALIX,and TSG101 in mice.Conclusions Houpu Sanwu decoction inhibits tumor growth and the secretion of exosomes,possibly by regulating Rab27a.

AIM: To prepare the model of diabetic retinopathy(DR)on the basis of the model of type 2 diabetes mellitus(T2DM)in rats, observe the preventive and protective effect of metformin on DR in T2DM rats and the effect on serum Cystatin C(Cys C), and discuss its mechanism.METHODS: A total of 120 male SD rats were selected and 30 rats were randomly divided into blank control group A(10 rats), T2DM group(10 rats)and metformin intervention group A(10 rats). The remaining 90 rats were randomly divided into three groups: blank control group B(30 rats), DR group(30 rats)and metformin intervention group B(30 rats). Except for blank control groups A and B, T2DM models were constructed in all other groups. After modeling, rats in metformin intervention group A were given metformin by gavage, and rats in blank control group A and T2DM group were given normal saline by gavage. After 3mo of intervention, fasting blood glucose(FBG)and fasting serum insulin(FINS)indexes of the three groups were measured respectively, and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated and analyzed; The serum Cys C, tumor necrosis factor-α(TNF-α), the levels of Interleukin-8(IL-8), vascular endothelial growth factor(VEGF)and reactive oxygen species(ROS)were measured, and we observed the retinal tissue and vascular morphology of rats by FFA, HE staining and transmission electron microscopy; rats in metformin intervention group B began to give metformin by gavage 3mo after the course of T2DM, and other rats were given normal saline. According to the length of intervention, 10 rats were taken from each group and observed at 4, 5 and 6mo respectively. Serum levels of Cys C, TNF-α, IL-8, VEGF and ROS were measured in each group. We observed the retinal tissue and vascular morphology of rats by FFA, HE staining and transmission electron microscopy.RESULTS: The expressions of serum FBG, FINS, HOMA-IR, Cys C, TNF-α, IL-8, VEGF and ROS were statistically significant among the blank control group A, T2DM group and metformin intervention group A(P<0.05), which were the highest in T2DM group, and the metformin intervention group A were lower than T2DM group; The expression of Cys C, TNF-α, IL-8, VEGF and ROS of rat serum were statistically significant among the blank control group B, DR group and metformin intervention group B within the same age groups at 4, 5 and 6mo respectively(P<0.05), and were all the highest in DR group. The expressions of metformin intervention group B were lower than those of the DR group. With the prolongation of DR course, the expression of Cys C, TNF-α, IL-8, VEGF and ROS also increased further; FFA results showed that compared with the corresponding blank control group, the retinal blood vessels of each model group were tortuous, and microaneurysms and fluorescence leakage were visible with the prolongation of the disease course; HE staining results showed that compared with the corresponding blank control group, the retinal cells of each model group were arranged disorderly, and abnormal dilated blood vessels were visible with the prolongation of the disease course; Transmission electron microscopy results showed that compared with the corresponding blank control group, the retinal capillaries in each model group were seriously damaged; However, compared with the corresponding model group, the results of FFA, HE and transmission electron microscopy of rats in each metformin intervention group had different degrees of improvement.CONCLUSIONS: Metformin can improve retinal tissue lesions by down-regulating serum Cys C-mediated levels of inflammation and oxidative stress, thus playing a preventive and therapeutic role in the retinopathy in T2DM rats.

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

Objective: To analyze the clinical characteristics of Wilson's disease (WD) with onset of acute liver failure (ALF) in children. Methods: Clinical data of 19 children diagnosed with WD presented with ALF in Xi'an Children's Hospital from January 2016 to April 2021 were retrospectively analyzed, including general condition, clinical manifestation, laboratory examination, and gene detection. The children were divided into the death group and survival group according to the clinical outcome. The children who had hepatic WD with non-ALF onset during the same period were selected as the control. The general conditions and laboratory indexes were compared between death group and survival group, ALF group and non-ALF group. T-test, Mann Whitney U test or χ² test were used to compare the differences between the two groups. Results: Of the 19 WD children with ALF onset, 10 were females and 9 were males. The age of admission was (10.1±2.6) years and time to onset of first visit was 9 (4, 15) days. Among the WD children with ALF onset, 4 children were lost to follow-up, 5 cases death (death group) and 10 cases survived (survival group). The ceruloplasmin in the death group was higher than that in the survival group (0.078 (0.055, 0.105) vs. 0.033 (0.027, 0.058) g/L, Z=-2.33, P=0.020). There were 95 children who had hepatic WD with non-ALF onset. The WD patients with ALF onset were older at admission (9.9 (8.0, 11.1) vs. 5.4 (3.7, 6.9) years, Z=-5.25, P<0.001), had higher ceruloplasmin (0.060 (0.030, 0.078) vs. 0.024 (0.006, 0.060) g/L, Z=-3.11, P=0.002), 24 h urinary copper (674 (205, 1 803) vs. 149 (108, 206) μg, Z=-4.25, P<0.001), and positive rate of K-F ring [17/19 vs. 7%(7/95), χ²=50.17, P<0.001] while shorter onset time at initial visit (0.3 (0.1, 0.5) vs. 1.0 (0.7, 6.0) months, Z=-4.28, P<0.001). There was no gender difference between the two groups [9/19 vs. 61%(58/95), χ²=1.22, P=0.269]. Of the 19 WD children with ALF onset, 13 had the ATP7B gene tested, and 15 reported variants were detected. The main variations were c.2333G>T (p. Arg778Leu), c.2621C>T (p. Ala874Val) and c.2975C>T (p. Pro992Leu). The allele frequencies were 6/26(23%), 4/26(15%) and 3/26(12%), respectively. Conclusions: Children of WD onset with ALF are school-aged and above. They have an acute onset, a short course of the disease, and poor prognosis. The positive rate of K-F ring, ceruloplasmin and urinary copper are higher than those of the hepatic WD children with non-ALF onset.
Ceruloplasmin/metabolism* ; Child ; Copper/metabolism* ; Female ; Hepatolenticular Degeneration/genetics* ; Humans ; Liver Failure, Acute/therapy* ; Male ; Retrospective Studies

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

p62 is a ubiquitous multifunctional protein with six domains in the body.p62 is mainly involved in selective autophagic degradation of ubiquitinated substrates.Hence, it has become an important biomarker of monitoring autophagic flux.p62 is also involved in oxidative stress.Additionally, p62 participates in series of cellular biological processes including nutrient sensing, apoptosis and metabolic reprogramming.The expression of p62 is regulated by some transcriptive factors such as TFEB.The mutations of p62 gene are associated with neurological and other disorders.It has been shown that p62 is necessary for maintaining normal function of glomerular podocytes, massangial cells and renal tubular cells.Based on the diversity and importance of p62 protein functions, it may turn to be a candidate of therapeutic target in renal diseases in future.

The epidemic caused by coronavirus poses a serious threat to human health, but there is no specific drug or vaccine for the treatment of this kind of virus infection. Herein, this article selects typical case studies in recent years and reviews the medicinal chemistry strategies of anti-SARS-CoV, MERS-CoV and other coronavirus drugs from the perspective of medicinal chemistry, and tries to provide some clues to current drug research againstSARS-CoV-2.

Objective To explore the determinants of infants overweight and obesity using generalized estimation equation (GEE). Methods Data were extracted from 26 624 2-year old infants who completed required health examination from January 2017 to December 2019 in Minhang District of Shanghai.The weight for height at 6, 12, 18 and 24 months of age was calculated to evaluate nutrition status of infants.Ordinal multinomial GEE was fitted with malnutrition, normality, overweight and obesity as responding variables to explore the determinants of infants overweight and obesity. Results Incidence rate of overweight and obesity in infants of 6 to 24 months of age had a tendency of decline, and proportion of normality showed as increasing tendency along with the increase of months of age(P < 0.001).GEE showed that the following factors were more likely involved in infant overweight and obesity: male(OR=1.182), lower education level of mother (OR=1.399 for primary school, OR=1.124 for junior high school, and OR＝1.083 for senior high school, respectively), higher body weight of father(OR=1.003), higher pre-pregnant body weight of mother(OR=1.003), longer gestational age(OR=1.058), longer sleeping time at 6 month of age(OR=1.032), lower month of age (OR=2.911 for 6 months, OR=1.952 for 12 months, and OR=1.232 for 18 months, respectively).Those with low birth weight (OR=0.205 for < 2 500 g, and OR=0.410 for 2 500~3 999 g, respectively)and exclusive breastfeeding at 6 months of age(OR=0.946)had low likelihood of overweight and obesity. Conclusion Comprehensive measures should be taken to control infants overweight and obesity, including encouraging expectant parents to maintain normal body weight before pregnancy, strengthening the education of scientific feeding knowledge, and extending exclusive breastfeeding.

BACKGROUNDInterferon-gamma release assay (IGRA) has been used in latent tuberculosis (TB) infection and TB diagnosis, but the results from different high TB-endemic countries are different. The aim of this study was to investigate the value of IGRA in the diagnosis of active pulmonary TB (PTB) in China.

METHODSWe conducted a large-scale retrospective multicenter investigation to further evaluate the role of IGRA in the diagnosis of active PTB in high TB-epidemic populations and the factors affecting the performance of the assay. All patients who underwent valid T-SPOT.TB assays from December 2012 to November 2015 in six large-scale specialized TB hospitals in China and met the study criteria were retrospectively evaluated. Patients were divided into three groups: Group 1, sputum culture-positive PTB patients, confirmed by positive Mycobacterium tuberculosis sputum culture; Group 2, sputum culture-negative PTB patients; and Group 3, non-TB respiratory diseases. The medical records of all patients were collected. Chi-square tests and Fisher's exact test were used to compare categorical data. Multivariable logistic analyses were performed to evaluate the relationship between the results of T-SPOT in TB patients and other factors.

RESULTSA total of 3082 patients for whom complete information was available were included in the investigation, including 905 sputum culture-positive PTB cases, 914 sputum culture-negative PTB cases, and 1263 non-TB respiratory disease cases. The positive rate of T-SPOT.TB was 93.3% in the culture-positive PTB group and 86.1% in the culture-negative PTB group. In the non-PTB group, the positive rate of T-SPOT.TB was 43.6%. The positive rate of T-SPOT.TB in the culture-positive PTB group was significantly higher than that in the culture-negative PTB group (χ2 = 25.118, P < 0.01), which in turn was significantly higher than that in the non-TB group (χ2 = 566.116, P < 0.01). The overall results were as follows: sensitivity, 89.7%; specificity, 56.37%; positive predictive value, 74.75%; negative predictive value, 79.11%; and accuracy, 76.02%.

CONCLUSIONSHigh false-positive rates of T-SPOT.TB assays in the non-TB group limit the usefulness as a single test to diagnose active TB in China. We highly recommend that IGRAs not be used for the diagnosis of active TB in high-burden TB settings.