Objective:To explore the incidence and mortality of digestive system cancers, and the trend of the disease burden attributed to different risk factors in population in China.Methods:Data were obtained from the GLOBOCAN 2020 and the Global Burden of Disease Study in 2019 databases and only the data from the Chinese population were included. Using Excel 2019 and R 4.2.1 software, indicators including age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized disability-adjusted life year (DALY) rate and its rate of change were used to illustrate the disease burden of digestive system cancers attributed to different factors and their trends.Results:In 2020, the ASIR of digestive system cancers in China was 83.00/100 000, and the ASMR was 63.80/100 000. The numbers of digestive system cancer cases and deaths increased with age, and more cases and deaths occurred in men than in women in all age groups. The age-standardized DALY rate of esophageal cancer, gastric cancer and liver cancers showed decreasing trends in China from 1990 to 2019 (rate of change: -45.26%, -46.87%, and -65.63%, respectively), whereas the age-standardized DALY rate of pancreatic cancer, colorectal cancer and gallbladder and biliary tract cancer showed increasing trends (rate of change: 67.61%, 30.52%, and 7.21%, respectively). The trend of the mortality rate was consistent with the DALY rate. Compared with the age-standardized DALY rate attributed to behavioral factors, the annual proportion of the age-standardized DALY rate attributed to metabolic factors to the total age-standardized DALY rate of esophageal cancer, liver cancer, pancreatic cancer, and colorectal cancer increased from 1990 to 2019. There was no significant change in the rank of age-standardized DALY rate of gastric cancer, liver cancer, pancreatic cancer, and gallbladder and biliary tract cancer attributed to different risk factors in China from 1990 to 2019, but the rank of certain attributed risk factors for the age-standardized DALY rate of esophageal cancer and colorectal cancer moved ahead (esophageal cancer: high BMI; colorectal cancer: low milk intake, and low whole-grain intake).Conclusions:The incidence and mortality of digestive system cancers was serious in China in 2020, and the annual proportion of the disease burden of digestive system cancers attributed to metabolic factors increased from 1990 to 2019. The rank of attributed risk factors for several digestive system cancers changed significantly.

Objective:To investigate the effect of GRIM-19 on the resistance of carcinoma cells to the chemotherapeutic agent docetaxel in the treatment of PCa.Methods:Using siRNA technology to interfere with the gene expression in PCa cells,we estab-lished a model of GRIM-19 overexpression/knockdown in PCa cells.We investigated the effect of different expression levels of GRIM-19 on docetaxel-induced death of the PCa cells by qPCR,Western blot and flow cytometry,and assessed the value of GRIM-19 in re-ducing the chemotherapy-resistance of PCa cells.Results:GRIM-19 was down-regulated in PCa tissues and cells.Knockout of GRIM-19 significantly decreased the expression of siGRIM19 in the PC-3 and LNCaP cells,and reduced their death rate when treated with docetaxel compared with the control group.The expressions of GRIM-19 mRNA and protein were remarkably upregulated after transfection with GRIM-19,and the overexpressed GRIM-19 promoted the death of the PC-3 and LNCaP cells treated with docetaxel in a dose-dependent manner.Flow cytometry analysis showed a lower apoptosis rate of PC-3-R cells than that of PC-3 cells at different time points of docetaxel-induction at different doses.Conclusion:GRIM-19 is a PCa suppressor gene with a significant facilitating effect on the apoptosis of PCa cells,and the overexpression of GRIM-19 promotes docetaxel-induced PCa cell death and improves the sensitivity of chemotherapy.

Objective To understand the distribution and antimicrobial resistance changes of bacteria isolated from pleural and peritoneal effusion in Hunan Province,and provide reference for correct clinical diagnosis and rational antimicrobial use.Methods Data reported by member units of Hunan Provincial Antimicrobial Resistance Survei-llance System from 2012 to 2021 were collected.Bacteria antimicrobial resistance surveillance method was imple-mented according to technical scheme of China Antimicrobial Resistance Surveillance System(CARSS),and WHO-NET 5.6 software was used to analyze the data of bacteria isolated from pleural and peritoneal effusion as well as antimicrobial susceptibility testing results.Results From 2012 to 2021,a total of 28 934 bacterial strains were iso-lated from specimens of pleural and peritoneal effusions from member units of Hunan Provincial Antimicrobial Re-sistance Surveillance System,with 5 752 strains from pleural effusion and 23 182 from peritoneal effusion.The top five bacteria isolated from pleural effusion were Escherichia coli(n=907,15.8％),Staphylococcus aureus(n=535,9.3％),Klebsiella pneumoniae(n=369,6.4％),Staphylococcus epidermidis(n=452,7.9％),and Staphy-lococcus haemolyticus(n=285,5.0％).The detection rate of methicillin-resistant Staphylococcus aureus(MR-SA)from pleural effusion was 24.3％-39.2％,and that of methicillin-resistant coagulase negative Staphylococcus(MRCNS)was 58.8％-77.1％.The top five bacteria isolated from peritoneal effusion were Escherichia coli(n=8 264,35.6％),Klebsiella pneumoniae(n=2 074,9.0％),Enterococcus faecium(n=1 458,6.3％),Staphylo-coccus epidermidis(n=1 383,6.0％),and Pseudomonas aeruginosa(n=1 152,5.0％).The detection rate of MRSA from peritoneal effusion was 22.1％-52.4％,which presented a decreasing trend(P=0.004).The detec-tion rate of MRCNS was 60.4％-79.4％.The resistance rates of Enterobacterales from peritoneal effusion to ce-fazolin,cefuroxime,ceftriaxone and cefepime all showed decreasing trends(all P＜0.05).Vancomycin-,linezo-lid-,and teicoplanin-resistant Staphylococcus strains were not found in pleural and peritoneal effusions.The resis-tance rates of Enterococcus faecium to most tested antimicrobial agents were higher than those of Enterococcus fae-calis.The resistance rates of Enterobacterales to imipenem and meropenem were ≤8.5％.The resistance rates of non-fermentative Gram-negative bacilli to imipenem and meropenem were ≤43.3％.Conclusion The data structure of Hunan Antimicrobial Resistance Surveillance System for pleural and peritoneal effusions from 2012 to 2021 is relatively complete.The constituent and antimicrobial susceptibility of isolated pathogenic bacteria vary in different years.

Objective To understand the epidemiology of clinically isolated Acinetobacter baumannii(A.bauma-nnii)in Hunan Province.Methods Bacterial antimicrobial resistance surveillance was carried out according to the requirements of the technical program of National Antimicrobial Resistance Surveillance System.Clinical data of Acinetobacter spp.reported to Hunan Provincial Antimicrobial Resistance Surveillance System by multiple centers in Hunan Province from 2012 to 2021 were summarized and analyzed with reference to the standards of the American Clinical and Laboratory Standards Institute.Results A total of 169 438 strains of Acinetobacter spp.were detected during the 10-year period,with the detection rate of A.baumannii being the highest(82.74％).70 923 strains(53.63％)of carbapenem-resistant A.baumannii(CRAB)and 58 149 strains(43.97％)of carbapenem-sensitive A.baumannii(CSAB)were detected respectively.Both CRAB and CSAB were detected most frequently in the age group＞70 years,which were 34.44％and 32.02％,respectively.The percentage of CRAB and CSAB detected in the intensive care unit were 34.80％and 11.31％,respectively.CRAB and CSAB were mainly isolated from spu-tum/bronchoalveolar lavage fluid,followed by pus/secretion,urine,and blood.The resistance rates of CRAB to commonly used antimicrobial agents didn't change much during the 10-year period.Resistance rates of CRAB to ceftazidime and cefepime were both＞84％,to ampicillin/sulbactam and piperacillin/tazobactam were both＞82％,to aminoglycosides and quinolones were both＞59％,to minocycline and polymyxin B were 15.9％-25.0％and 1.3％-6.9％,respectively.CSAB were sensitive to commonly used antimicrobial agents.Conclusion The isolation rate of CRAB is high and there is no significant change in resistance to commonly used antimicrobial agents.

OBJECTIVE: To investigate the efficacy and safety of venetoclax (VEN) combined with demethylating agents (HMA) in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML). METHODS: The clinical data of 26 adult R/R AML patients who received the combination of VEN with azacitidine (AZA) or decitabine (DAC) in Huai'an Second People's Hospital from February 2019 to November 2021 were retrospectively analyzed. The treatment response, adverse events as well as survival were observed, and the factors of influencing the efficacy and survival were explored. RESULTS: The overall response rate (ORR) of 26 patients was 57.7% (15 cases), including 13 cases of complete response (CR) and CR with incomplete count recovery (CRi) and 2 cases of partial response (PR). Among the 13 patients who got CR/CRi, 7 cases achieved CRm (minimal residual disease negative CR) and 6 cases did not, with statistically significant differences in overall survival (OS) and event-free survival (EFS) between the two groups (P=0.044, 0.036). The median OS of all the patients was 6.6 (0.5-15.6) months, and median EFS was 3.4 (0.5-9.9) months. There were 13 patients in the relapse group and refractory group, respectively, with response rate of 84.6% and 30.8% (P=0.015). The survival analysis showed that the relapse group had a better OS than the refractory group (P=0.026), but there was no significant difference in EFS (P=0.069). Sixteen patients who treated for 1-2 cycles and 10 patients who treated for more than 3 cycles achieved response rates of 37.5% and 90.0%, respectively (P=0.014), and patients treated for more cycles had superior OS and EFS (both P<0.01). Adverse effects were mainly bone marrow suppression, complicated by various degrees of infection, bleeding, and gastrointestinal discomfort was common, but these could be all tolerated by patients. CONCLUSION VEN combined with HMA is an effective salvage therapy for patients with R/R AML and is well tolerated by patients. Achieving minimal residual disease negativity is able to improve long-term survival of patients.
Adult ; Humans ; Retrospective Studies ; Neoplasm, Residual/drug therapy* ; Bridged Bicyclo Compounds, Heterocyclic/adverse effects* ; Recurrence ; Leukemia, Myeloid, Acute/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Objective:To study peripheral nerve morphology in patients with transthyretin familial amyloid polyneuropathy (TTR-FAP) using high-frequency ultrasonography (HFUS), and to evaluate the value of HFUS in diagnosis of TTR-FAP.Methods:Thirty-eight patients with TTR-FAP diagnosed by gene detection and 23 normal controls from June 2015 to June 2021 in Peking University First Hospital were enrolled in this study. Consecutive ultrasonography scanning was performed in 6 pairs of nerves of bilateral limbs with 30 sites. The cross sectional area (CSA), CSA variability and inter-nerve CSA variability data of the two groups were retrospectively calculated and compared.Results:Compared with the normal controls, TTR-FAP patients showed larger CSA values at most nerve sites of both upper and lower limbs, and there were statistically significant differences at M1(median nerve) [8.55 (6.90, 9.40) mm 2vs 10.05 (9.10, 14.10) mm 2, Z=5.58, P<0.001], M3 (median nerve) [(6.98±1.66) mm 2vs (9.29±2.30) mm 2, t=6.28, P<0.001], M5 (median nerve) [(8.91±1.81) mm 2vs (14.33±4.20) mm 2, t=9.84, P<0.001], U5 (ulnar nerve) [(6.20±1.93) mm 2vs (9.34±2.85) mm 2, t=7.31, P<0.001], Sci1 (sciatic nerve) [(53.50±17.24) mm 2vs (79.74±20.75) mm 2, t=7.57, P<0.001], Sci2 (sciatic nerve) [(53.66±14.21) mm 2vs (73.98±19.21) mm 2, t=6.82, P<0.001] and Tib (tibial nerve) [(31.05±8.43) mm 2vs (46.29±13.14) mm 2, t=7.84, P<0.001] sites. There was no statistically significant difference in CSA at each site among the different subtypes and disease severity of TTR-FAP patients ( P>0.05). There was no statistically significant difference in CSA-variability of the median and ulnar nerves between the patients with TTR-FAP and the normal controls ( P>0.05). The side-to-side difference ratio of intra-nerve CSA variability of the ulnar nerve in the patients with TTR-FAP was smaller than that of the normal controls (1.15±0.10 vs 1.46±0.43, t=3.43, P=0.002), whereas no statistically significant difference of that in the median nerve was found between the two groups ( P>0.05). Conclusions:The most pronounced peripheral nerve thickening in the proximal limb segments with no signs of asymmetric distribution or lateralization is confirmed by HFUS in TTR-FAP patients and should be regarded as a marker of TTR-FAP. HFUS has clinical value in diagnosis of peripheral neuropathy in TTR-FAP patients.

OBJECTIVES: To study the characteristics of amino acid metabolism in preterm infants in Guangxi, China. METHODS: A retrospective analysis was performed on the medical data of 30 757 neonates who underwent the screening for inherited metabolic diseases and had negative results in Guangxi Neonatal Disease Screening Center from 2018 to 2020. Among these neonates, there were 28 611 normal full-term infants (control group) and 2 146 preterm infants (preterm birth group). According to gestational age, the preterm infants were further divided into four groups: very preterm (n=209), moderately preterm (n=307), and late preterm group (n=1 630). According to birth weight, they were divided into three groups: very low birth weight group (n=161), low birth weight group (n=1 085), and normal birth weight group (n=900). According to blood collection time, they were divided into three groups: 3-7 days group (n=1 664), 8-14 days group (n=314) and 15-28 days group (n=168). Tandem mass spectrometry was performed to measure the levels of 11 amino acids in dried blood spots, which were then compared between groups. RESULTS: After adjustment for confounding factors, there were significant differences in the levels of 11 amino acids among different gestational age groups (P<0.05), and significant differences were observed in the levels of the 11 amino acids between the control group and the various preterm groups (except for citrulline and methionine in the late preterm group). There were significant differences in the levels of 11 amino acids among different birth weight groups (P<0.05). Except for ornithine, there were significant differences in the levels of other amino acids among the different blood collection time groups (P<0.05). CONCLUSIONS Gestational age, birth weight and blood collection time all affect amino acid metabolism in preterm infants in Guangxi, China. This provides a basis for the laboratory to establish the reference standard and clinical interpretation of blood amino acid levels in preterm infants, and to improve the nutritional metabolism of preterm infants.
Amino Acids ; China ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Premature Birth ; Retrospective Studies

Long non-coding RNAs (LncRNAs) are abnormally expressed in a variety of tumors and participate in the occurrence and development of tumors. However, the expression and function of many LncRNAs in tumors have not been fully clarified. In this paper, 113 normal breast tissues and 1 109breast cancer tissues were analyzed in TCGT database. LncRNA AL133467. 1 was found to be lowly expressed in breast cancer tissues and negatively correlated with poor prognosis of breast cancer patients. The expression of AL133467. 1 in breast cancer cells was significantly lower than that in normal breast epithelial cells. We overexpressed AL133467. 1 in relatively low-expression breast cancer cells SKBR3and BT474, and cell count and plate colony-formation experiments showed that overexpression ofAL133467. 1 could significantly inhibit the proliferation and colony formation of breast cancer cells (P< 0. 01). Cell scratch and Transwell assays showed that the migration and invasion ability of breast cancer cells overexpressing AL133467. 1 was significantly reduced compared with the control group (P<0. 01). MiRDB database showed that AL133467. 1 had binding sites with miR-661. miR-661 could bind the transducer of ErbB2, 2 (ErbB2, 2, TOB2). qRT-PCR showed that miR-661 was highly expressed inbreast cancer cells and positively correlated with poor prognosis of breast cancer patients (P < 0. 001). Luciferase reporter assays showed that AL133467. 1 had specific binding to miR-661 (P < 0. 01). AL133467. 1 overexpression could inhibit the expression of miR-661 in breast cancer cells (P<0. 0001). Transfection of miR-661 mimics eliminated the inhibitory effect of overexpression of AL133467. 1 on breast cancer cells (P < 0. 001). In addition, qRT-PCR and Western blotting results showed that overexpression of AL133467. 1 up-regulated TOB2 mRNA (P < 0. 0001) and protein levels. But whenmiR-661 mimics were transfected, TOB2 mRNA (P < 0. 0001) and protein levels were significantly inhibited. In conclusion, as a competitive endogenous RNA of miR-661. AL133467. 1 promotes the expression of TOB2, thereby inhibiting the proliferation and invasion of breast cancer cells.

The purpose of the present study was to investigate the effect of glutamate scavenger oxaloacetate (OA) combined with CGS21680, an adenosine A2A receptor (A2AR) agonist, on acute traumatic brain injury (TBI), and to elucidate the underlying mechanisms. C57BL/6J mice were subjected to moderate-level TBI by controlled cortical impact, and then were treated with OA, CGS21680, or OA combined with CGS21680 at acute stage of TBI. At 24 h post TBI, neurological severity score, brain water content, glutamate concentration in cerebrospinal fluid (CSF), mRNA and protein levels of IL-1β and TNF-α, mRNA level and activity of glutamate oxaloacetate aminotransferase (GOT), and ATP level of brain tissue were detected. The results showed that neurological deficit, brain water content, glutamate concentration in CSF, and the inflammatory cytokine IL-1β and TNF-α production were exacerbated in CGS21680 treated mice. Administrating OA suppressed the rise of both glutamate concentration in CSF and brain water content, and elevated the ATP level of cerebral tissue. More interestingly, neurological deficit, brain edema, glutamate concentration, IL-1β and TNF-α levels were ameliorated significantly in mice treated with OA combined with CGS21680. The combined treatment exhibited better therapeutic effects than single OA treatment. We also observed that GOT activity was enhanced in single CGS21680 treatment group, and both the GOT mRNA level and GOT activity were up-regulated in early-stage combined treatment group. These results suggest that A2AR can improve the efficiency of GOT and potentiate the ability of OA to metabolize glutamate. This may be the mechanism that A2AR activation in combination group augmented the neuroprotective effect of OA rather than aggravated the brain damages. Taken together, the present study provides a new insight for the clinical treatment of TBI with A2AR agonists and OA.
Adenosine A2 Receptor Agonists/therapeutic use* ; Adenosine Triphosphate ; Animals ; Brain Injuries/metabolism* ; Brain Injuries, Traumatic/metabolism* ; Glutamic Acid ; Mice ; Mice, Inbred C57BL ; Neuroprotective Agents/therapeutic use* ; Oxaloacetic Acid/therapeutic use* ; RNA, Messenger ; Receptor, Adenosine A2A/metabolism* ; Tumor Necrosis Factor-alpha/genetics* ; Water

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).
Adult ; Humans ; Secondary Prevention/methods* ; Ischemic Stroke ; Stroke/prevention & control* ; Cerebral Hemorrhage/complications* ; Double-Blind Method ; Platelet Aggregation Inhibitors