OBJECTIVE To explore the clinical characteristics of cardiotoxicity caused by lidocaine， and provide a reference for the safe use of drug in clinical practice. METHODS Chinese and English search terms， such as “lidocaine”“ cardiotoxicity”， were used to search for literature related to lidocaine-induced cardiac toxicity from CNKI， Wanfang Data， VIP， PubMed and Embase， and conduct descriptive analysis. RESULTS A total of 31 papers were included， with 40 patients. Of the 40 patients， 23 were male and 17 were female； ages ranged from 5 months to 73 years， with 4 patients≤18 years old， 17 patients 19-59 years old， and 19 patients≥60 years old. The main indications for medication were surgical anesthesia （26 cases）， and the main routes of administration were intravenous administration， nerve block anesthesia and local infiltration anesthesia （15， 6， 6 cases）； the dosage of medication for 34 patients complied with the instructions； the most of cardiotoxicity occurred 1 min-1 h after medication （19 cases）， and the main symptoms were bradycardia， atrial conduction slowing， atrioventricular block， sinus arrest， etc. Thirty- four patients improved after resuscitation and symptomatic treatment， and six patients died. CONCLUSIONS Lidocaine-induced cardiotoxicity can occur in all ages， mainly within 1 h after administration， and is manifested as arrhythmia， tachycardia or tachycardia， atrioventricular block， etc.， which is severe. When using it clinically， it is necessary to strengthen pharmaceutical monitoring of medication dosage， administration route， toxic reactions， etc.； when relevant symptoms appear， medication should be stopped promptly and symptomatic treatment should be carried out， to protect the safety of drug use.

OBJECTIVE To explore the clinical characteristics of cardiotoxicity caused by lidocaine， and provide a reference for the safe use of drug in clinical practice. METHODS Chinese and English search terms， such as “lidocaine”“ cardiotoxicity”， were used to search for literature related to lidocaine-induced cardiac toxicity from CNKI， Wanfang Data， VIP， PubMed and Embase， and conduct descriptive analysis. RESULTS A total of 31 papers were included， with 40 patients. Of the 40 patients， 23 were male and 17 were female； ages ranged from 5 months to 73 years， with 4 patients≤18 years old， 17 patients 19-59 years old， and 19 patients≥60 years old. The main indications for medication were surgical anesthesia （26 cases）， and the main routes of administration were intravenous administration， nerve block anesthesia and local infiltration anesthesia （15， 6， 6 cases）； the dosage of medication for 34 patients complied with the instructions； the most of cardiotoxicity occurred 1 min-1 h after medication （19 cases）， and the main symptoms were bradycardia， atrial conduction slowing， atrioventricular block， sinus arrest， etc. Thirty- four patients improved after resuscitation and symptomatic treatment， and six patients died. CONCLUSIONS Lidocaine-induced cardiotoxicity can occur in all ages， mainly within 1 h after administration， and is manifested as arrhythmia， tachycardia or tachycardia， atrioventricular block， etc.， which is severe. When using it clinically， it is necessary to strengthen pharmaceutical monitoring of medication dosage， administration route， toxic reactions， etc.； when relevant symptoms appear， medication should be stopped promptly and symptomatic treatment should be carried out， to protect the safety of drug use.

Objective:To explore the association between postoperative radiotherapy for bladder cancer and the risk of second primary rectal cancer.Methods:Eligible 75 120 patients with bladder cancer from the Surveillance, Epidemiology, and End Result database (SEER) of the National Cancer Institute (NCI) (1975-2017) were enrolled in this study. The second primary cancers referred to rectal cancers patients suffered after more than five years post-treatment for bladder cancer, and the cumulative incidence was estimated using Fine-Gray competing risk regression. The relative risk (RR) of rectal cancer in patients treated with or without radiotherapy (the RT group or the NRT group) was evaluated using Poisson regression.Results:Among the 75 120 patients, 70 045 (92.4%) were Caucasian, with a median age of 65.8 years (54-74 years). A total of 2 236 (3%) received postoperative radiotherapy, while 72 884 (97%) received surgery alone. The 30-year follow-up revealed a cumulative incidence of rectal cancer of 0.93% in the RT group and 0.43% in the NRT group ( P = 0.004). The competing risk regression analysis identified a significant association between radiotherapy and rectal cancer ( HR: 1.86; 95% CI 1.26-2.74, P < 0.009). Furthermore, the RR of radiotherapy-associated rectal cancer significantly increased as the diagnosis occurred earlier (1975-1985 vs. 1985-1994: RR 2.59; 95% CI 1.20-4.86, P < 0.001), and a lower age at the time of radiotherapy was associated with a higher probability of second primary tumors (≤50-year old vs. > 50 year old : RR 7.89, 95% CI 2.97-21.30, P < 0.001). As calculated using the Poisson distribution, the RR of second rectal tumors was higher in the RT group ( RR: 2.20, 95% CI 1.45-3.18, P < 0.001), even after adjusting the date of diagnosis ( RR: 1.77, 95% CI 1.17-2.57, P = 0.009). Conclusions:An increased risk of rectal cancer following bladder cancer radiotherapy necessitates aggressive follow-ups for the purpose of early detecting second primary rectal cancer associated with bladder cancer radiotherapy.

Objective:To analyze the detection strategy and basic detection situation of markers of infectious diseases transmitted by transfusion in blood testing laboratories of blood stations in China.Methods:Based on the data of practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021, the data on the testing strategies and the basic detection information of the markers for the transmission of infectious diseases through transfusion in the member laboratories of the practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021 were collected, and the situation of the selection for testing markers, testing strategy and the testing method and other relevant aspects were sorted out and analyzed by charts.Results:The selection of the testing markers was consistent, but HTLV testing item was added in some member laboratories. The detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously was adopted in 47 member blood stations; 3) NAT method was dominated by mini pool-NAT in member laboratories. The number of members adopting mini-pools of 8 (MP8)-NAT decreased from 17 in 2017 to 14 in 2021, while the number of members adopting mini-pools of 6 (MP6)-NAT increased from 13 in 2017 to 22 in 2021; Roche NAT system accounted for the largest proportion.Conclusions:In order to ensure blood safety and avoid missing detection, the blood stations still adopt the detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously; Meanwhile, in order to increase the NAT positive rate, the proportion of mini pool-NAT mainly decreased year by year despite its dominating role, while the proportion of individual donation-NAT increased year by year; NAT method is transiting from mini-pools of 8 (MP8) to mini-pools of 6 (MP6); The proportion of imported NAT system used in NAT laboratory is relatively large.

The relationship between pyroptosis and immune microenvironment and disease has received increasing attention. Pyroptosis plays a dual role in anti-tumor immunotherapy by promoting the release of inflammatory factors, forming the tumor microenvironment and suppressing tumour immunity on the one hand, and inducing the tumour inflammatory response to inhibit the proliferation of tumor cells on the other hand. The relationship between pyroptosis, immune microenvironment and tumors is different in different tissues and genetic backgrounds. This article reviews the molecular mechanisms of pyroptosis and the regulatory role of tumor immune microenvironment in hematologic malignancies, with a view to providing ideas for the anti-hematologic malignancies treatment and research based on the target of pyroptosis-regulated immune microenvironment.

Objective: To investigate the effect and the mechanism of Astragalus membranaceus (Huangqi in Chinese, HQ) extract on the intestinal absorption of six alkaloids of Aconitum carmichaelii (Fuzi in Chinese, FZ) in rats with spleen deficiency and provide novel insights into the application of HQ on modulating intestinal barrier. Methods: Four-week-old male Sprague-Dawley rats were fed with Xiaochengqi Decoction to induce the spleen deficiency model for 40 d. Single-pass intestinal perfusion model were used to study the effects of HQ extract on the absorption of alkaloids. Protein expression and mRNA levels of MRP2 and BCRP and tight junction proteins (TJ, including Claudin-1, Occludin and ZO-1) were measured using Western blot and real-time PCR, respectively. The location and expression of TJ protein was also investigated by the immunofluorescence method. Results: Compared with the normal group, the protein expression of MRP2, BCRP and TJ proteins in the model group were significantly down-regulated. After oral administration of HQ, the alkaloid absorption in intestinal villi was inhibited, MRP2, BCRP and TJ proteins were up-regulated, the green fluorescence staining of Claudin-1, Occludin, and ZO-1 was enhanced, and a thick layer of mucus was deposited on the surface of the epithelium of the intestinal cavity. Conclusion: HQ as an intestinal barrier modulator improves the physiological changes of the intestinal environment of spleen deficiency to reduce the absorption of toxic components, leading to a decrease in the absorption of drug-like molecules.

Colorectal cancer (CRC), a malignant tumor worldwide consists of microsatellite instability (MSI) and stable (MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types of tumor microenvironment (TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68⁺ macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively, our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.

Massive open online courses (MOOC) is an emerging teaching mode based on website, which has been developed rapidly in China since 2013. Contemporary medical education, assisted by MOOC, diverges greatly with various modes. In this paper, the current situation and advantages of MOOC on medical education in the information age were analyzed, and suggestions for improvement of MOOC on modern medical education were proposed in combination with foreign case study, which is conducive to the reform and innovation of medical education model.

Objective To investigate any protective effect of low-intensity pulsed ultrasound (LIPUS) and pioglitazone on chondrocytes in osteoarthritic patients using the pathway from peroxisome proliferator-activated γreceptor (PPARγ) to nuclear factor kappa B (NF-κB) to inducible nitric oxide synthase (iNOS).Methods Normal chondrocytes of 24 healthy adult New Zealand white rabbits were extracted and divided into a normal group,a lipopolysaccharide (LPS) group,a LIPUS group (LPS+LIPUS) and a pioglitazone group (LPS+pioglitazone),each of 6 using a random number table.Each group was given the intervention their names implies.The levels of tumor necrosis factor-α (TNF-α),leptin (LEP) and nitric oxide (NO) in the chondrocytes were detected using enzyme-linked immune sorbent assays.The expression of type Ⅱ collagen (COL2) in the chondrocytes of each groups was detected using immunocytochemistry and fluorescent staining.The mRNA and protein expressions of PPARγ,NF-κB and iNOS were detected using reverse transcription polymerase chain reactions and western blotting respectively.Results Compared with the LPS group,the average level of TNF-α,LEP and NO in the LIPUS and pioglitazone groups was significantly lower,with the levels in the pioglitazone group significantly lower than in the LIPUS group.Compared with the LPS group,COL2 expression in the LIPUS group was significantly greater.The mRNA and protein expressions of PPARγ in the chondrocytes in the LIPUS and pioglitazone groups were significantly higher than those in the LPS group.Compared with the LPS group,the mRNA and protein expressions of NF-κB and iNOS in the pioglitazone and LIPUS groups were significantly lower,with the pioglitazone group's levels significantly below those of the LIPUS group.Conclusion LIPUS and pioglitazone may promote anti-inflammatory action and COL2 synthesis in chondrocytes through the PPARγ/ NF-κB/iNOS pathway and play a protective role,at least in rabbits.

Objective To observe the effect of low intensity pulsed ultrasound (LIPUS) on chondrocytes co-cultured with infrapatellar fat pads.Methods Twenty-four infrapatellar fat pads and cartilages from female knee trauma patients aged between 25 and 35 were cut and stained using hematoxylin-eosin staining.Chondrocytes were isolated from part of the integrated surface of the cartilages to be cultured in vitro.They were then randomly divided into a normal chondrocyte group (the control group),a normal chondrocyte+FCM (fat conditioned medium) group (the model group),a normal chondrocyte+ FCM + LIP US group (the treatment group),and a normal chondrocyte+ FCM + LIPUS + GRGDSP (an integrin inhibitor) group (the inhibited group).The treatment group and inhibited group received LIPUS at 40 mW/cm2 for 20 min once a day,while the other groups received sham LIPUS treatment.Five days later,the cells were collected and western blotting was used to examine the expression of type Ⅱ collagen (COL2),aggrecan (Acan),matrixmetalloproteinase (MMP)-13,integrin β1,phosphorylation-focal adhesion kinase (p-FAK) and phosphorylation p38 (p-p38).Results Western blotting showed that compared with the control group,the expression of COL2 and Acan was significantly lower in the model group,but that of MMP-13,integrin β1,p-FAK and p-p38 was significantly higher.As compared with the model group,the expression of COL2,Acan,integrin β1 and p-FAK was significantly higher,and that of MMP-13 and p-p38 was significantly lower in the treatment group.The expression of COL2,Acan,MMP-13,integrin β1,p-FAK and p-p38 showed no significant difference between the inhibited and model groups,but that of COL2,Acan,MMP-13,integrin β1,p-FAK and p-p38 was significantly different between the control and treatment groups.Conclusions LIPUS provides a protective effect on chondrocytes through inhibiting the expression of MMP-13 induced by adipokines and the degradation of COL2 and Acan through activating the integrin-FAK-p38 MAPK pathway.