BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Objective: To deliver macro understanding of the latest research progress on clinical trials and approved products of cancer drugs in China in 2019. Methods: The number of clinical trials and related investigational products by domestic and foreign enterprises in 2019 were acquired in the China Food and Drug Administration Registration and Information Disclosure Platform for Drug Clinical Studies, while listed drugs were obtained in the China Food and Drug Administration Query System for Domestic and Imported Drug. Characteristics on stage, scope, indication of those trials, classification and mechanism of involved products, as well as listed anticancer drugs were summarized and depicted. Results: There were 474 cancer drug trials registered in China in 2019, accounting for 21.8% of the total, and 397 (83.8%) were initiated by domestic pharmaceutical enterprises. Overall, international multicenter trials accounted for 13.1%, and phase I trials accounted for 47.3%. Compared with global enterprises, the proportion of international multi-center trials initiated by domestic companies is lower (4.8% vs. 55.8%, P<0.001), and the proportion of phase I clinical trials and bioequivalence trials is higher (51.9% vs. 23.4%, 19.4% vs. 1.3%, P<0.001). An accumulative of 27 cancer types were involved for all the cancer drug trials, and lung cancer, solid tumor, and breast cancer were the most common cancer types, with 103, 95 and 49 trials, respectively. For the three cancer types unique to Chinese population, gastric, liver and esophageal cancer, the total number of initiated trials was 47. For all those trials, there were 335 cancer drug varieties, with 86.0% developed by domestic pharmaceutical enterprises, including 300 therapeutic drugs, 30 adjunctive drugs and 5 preventive drugs. In terms of mechanism, targeted drugs and immune drugs were the most popular, accounting for 74.6% and 20.3%, respectively. In addition, 17 anticancer drugs targeting on 11 cancer types were approved in China in 2019. Conclusions Clinical trials on cancer drugs in China have ushered a booming era, with large number of innovative agents represented by targeted drugs and immune drugs under clinical development or putting into clinical practice. Those local enterprises are playing more and more critical roles. Strengthening clinical research and development on Chinese unique cancer types is the key direction of future work.

A 8-channel neural signal′s simultaneous transducer detection micro system was developed to research the neural loop located at the brain hippocampus zone. The components of the system contained the neural probe manufactured with the Micro-electro-mechanical-systems (MEMS) technique based on silicon-on-insulator (SOI) substrate, biological low noise chopper-stabilization amplifier, low noise and intermediate speed SAR-ADC converter, reduced and low power ASK/FSK modulation radio transmitter. The micro system was applicable with the characters of small volume, interferences free, neural electrophysiology and neurotransmitter simultaneous detection, high sensitivity, high linearity, etc. The electrode resistance was optimized to 35.0 kΩ after depositing nanometer platinum black on the 4 electrophysiological sites on the Pt electrode. With the modification enzyme technique, nanomaterial enzyme membrane (Pt-mPD-GluOx) was directly fixed on the glutamate detection locus for selectively detecting special neural neurotransmitter matter. In addition, the electrochemistry measurement results indicated that the linear range of glutamate was 6-35 μmol/L with correlation coefficient of 0.97, the sensitivity was 0.0069 pA/(μmol/L). The current response error was less than 3.0 pA, which showed that the neural needle satisfied differential selection. Also, the logic/analog mixed signal 180-nm Application specific integrated circuit (ASIC ) technique (SmicRF180 nm 1Poly6M) was used to manufacture the transducer back-end disposing IC chip, and the test results provided some key parameters such as chopper-stabilization amplifier (equivalent in putting noise voltage ≤0.7 μV rms@1 kHz, gain of 71-82 dB, CMRR/PSRR>100 dB), SAR-ADC (ENOB is 12 bits, power consumption is 1.2 mW when maxmium conversion speed is 1 Msps, signal-noise-ratio is 60.9 dB, etc), and ASK/FSK modulation radio transmitter (the PA′s outputting power of 4-5 dBm, the radiation range of 10 meters). The micro neural transducer integrated system was convenient and wireless wearable for the research of brain hippocampus region.

Objective The aim of this study was to investigate the effects of Rad9 mutants with impaired DNA mismatch repair ( MMR) function on the tumorigenesis of colorectal cancer. Methods The colorectal cancer tumor samples were collected from 100 patients. The mutation profiles of human Rad9 ( hRad9) gene in these samples were detected by reverse transcriptase?polymerase chain reaction ( RT?PCR) and sequencing. The plasmid of pFLAG?hRad9 ( L101M ) was constructed following the QuickChange mutagenesis procedure and transfected into mRad9?deleted mouse cells ( mRad9-/- cells) . The expression of hRad9 protein was measured by western blot analysis. The MMR activity in live cells was detected by flow cytometry using the reporter plasmid for MMR function. Results Mutation from Leu to Met at the residue 101 ( L101M) of hRad9 gene was detected in 7 of the 100 samples. The mismatch repair efficiency of mRad9-/-+L101M cells ( mRad9?deleted mouse cells with ectopic expression of L101M hRad9 gene) was (34.0± 5. 6)%, which was significantly lower than that in the mRad9-/-+ hRad9 cells [ mRad9?deleted mouse cells with ectopic expression of hRad9 gene, (48.0±7.5)%, P<0.05]. After N?nitroso?N?methylurea (MNU) treatment, the survival rate of mRad9-/-+L101M cells was (33.7±5.9)%, which was significantly higher than that in the mRad9-/-+ hRad9 cells [(21.3±4.7)%, P<0.05]. Thus, ectopic expression of L101M hRad9 gene resulted in significantly reduced MMR activity and increased resistance to MNU. Furthermore, ectopic expression of hRad9 gene with mutation at the target residues of post?translational modification in mRad9-/- cells also led to a reduced MMR activity. Conclusion Rad9 mutants with impaired DNA mismatch repair function may promote tumorigenesis of colorectal cancer.

Objective The aim of this study was to investigate the effects of Rad9 mutants with impaired DNA mismatch repair ( MMR) function on the tumorigenesis of colorectal cancer. Methods The colorectal cancer tumor samples were collected from 100 patients. The mutation profiles of human Rad9 ( hRad9) gene in these samples were detected by reverse transcriptase?polymerase chain reaction ( RT?PCR) and sequencing. The plasmid of pFLAG?hRad9 ( L101M ) was constructed following the QuickChange mutagenesis procedure and transfected into mRad9?deleted mouse cells ( mRad9-/- cells) . The expression of hRad9 protein was measured by western blot analysis. The MMR activity in live cells was detected by flow cytometry using the reporter plasmid for MMR function. Results Mutation from Leu to Met at the residue 101 ( L101M) of hRad9 gene was detected in 7 of the 100 samples. The mismatch repair efficiency of mRad9-/-+L101M cells ( mRad9?deleted mouse cells with ectopic expression of L101M hRad9 gene) was (34.0± 5. 6)%, which was significantly lower than that in the mRad9-/-+ hRad9 cells [ mRad9?deleted mouse cells with ectopic expression of hRad9 gene, (48.0±7.5)%, P<0.05]. After N?nitroso?N?methylurea (MNU) treatment, the survival rate of mRad9-/-+L101M cells was (33.7±5.9)%, which was significantly higher than that in the mRad9-/-+ hRad9 cells [(21.3±4.7)%, P<0.05]. Thus, ectopic expression of L101M hRad9 gene resulted in significantly reduced MMR activity and increased resistance to MNU. Furthermore, ectopic expression of hRad9 gene with mutation at the target residues of post?translational modification in mRad9-/- cells also led to a reduced MMR activity. Conclusion Rad9 mutants with impaired DNA mismatch repair function may promote tumorigenesis of colorectal cancer.