BACKGROUND:silencing information regulatory 1(SIRT1)regulates the function of related proteins in chondrocytes in a deacetylated manner and participates in chondrocyte proliferation and differentiation,thereby promoting cartilage defect repair. OBJECTIVE:To screen for signaling pathways with unclear action status after SIRT1 gene knockdown in chondrocytes,as well as diseases or functions that produce changes using high-throughput technology. METHODS:ATDC5 chondrocytes from mice in logarithmic growth phase were divided into two groups:the cells were transfected with SIRT1 gene knockdown negative control lentivirus in control group and SIRT1 gene knockdown lentivirus in experimental group.GeneChip? Mouse Genome 430 2.0 Array was used to detect the mRNA expression at 72 hours after transfection.Applied bioinformatics technology was also used to screen for unclear activation or inhibition signaling pathways and their related factors.Moreover,enrichment of disease or function modules was analyzed. RESULTS AND CONCLUSION:After knocking down the SIRT1 gene,there were 245 signaling pathways with unclear activation or inhibition status in the mouse ATDC5 chondrocytes.According to the ranking of-Log(P-value),we reported the factors in the top 20 signaling pathways with unclear activation or inhibition status,including IGFBP4,TGFBR1,CTGF,COL4A5,LHX2,IL1RL1,and KLF6.According to the ranking of-Log(P-value),there were significant changes in 14 disease or function modules,including cellular growth and proliferation,organism survival,cell death and survival.According to the number of differentially expressed genes,there were significant changes in three disease or function modules,including organismal injury and abnormalities,cancer,and cell death and survival.According to the comprehensive ranking of-Log(P-value)and the number of differentially expressed genes,the disease or function module related to intrinsic immune response was significantly activated.

Objective To observe the efficacy of hepatic artery infusion chemotherapy(HAIC)combined with lenvatinib for treating Barcelona clinic liver cancer(BCLC)stage B or C hepatocellular carcinoma(HCC),and to explore the impact factors of patients'survival time.Methods Data of 104 patients with BCLC stage B or C HCC were retrospectively analyzed.The patients were divided into observation group(n=46,underwent HAIC combined with lenvatinib)and control group(n=58,underwent HAIC alone).The clinical efficacy and adverse reactions of treatments,as well as patients'overall survival(OS)and progression free survival(PFS)were recorded and compared between groups.Cox regressions were used to explore the impact factors of patients'survival time.Results Three months and 6 months after HAIC,the results of modified response evaluation criteria in solid tumors(mRECIST)in observation group were both better than those in control group(both P＜0.05),while no significant difference was found between groups one year after HAIC(P＞0.05).The overall survival rate in observation group was higher than that in control group(P＜0.05),while there was no significant difference of progression free survival rate between groups(P＞0.05).The incidence of rash in observation group was higher than that in control group(P＜0.05).Multiple Cox regression showed prolonged OS in HCC patients in observation group(hazard ratio[HR]=0.425,95%CI[0.255,0.791])compared with that in control group.Compared with pre-treatment Eastern Cooperative Oncology Group(ECOG)score 1,AFP≥400 μg/ml,the number of tumor foci≥3 and BCLC stage C,pre-treatment ECOG score 0,AFP＜400 μg/ml,the number of tumor foci≤2 and BCLC stage B were all independent protective factors of OS in HCC patients(all P＜0.05).Conclusion HAIC combined with lenvatinib was safe and effective for treating BCLC stage B or C HCC.Pre-treatment ECOG score,serum AFP level,the number of tumor foci and BCLC stage were all independent impact factors of OS.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Objective:To evaluate the associations of meeting intensive systolic blood pressure (SBP) control goals with risk for incident cardiovascular and cerebrovascular diseases among the adult hypertensive patients in China.Methods:We used data from adult hypertensive patients from the China Kadoorie Biobank. logistic regression models evaluated the influencing factors of meeting intensive and standard SBP control goals. Cox proportional hazard models evaluated the associations between meeting intensive vs. standard SBP control goals and risk for incident cardiovascular and cerebrovascular diseases.Results:A total of 3 628 hypertensive patients who reported continuous medication use were included in this study, of which 5.0% of the participants met the goals of intensive SBP control (≤130 mmHg). Participants with higher educational attainment ( OR=2.36,95% CI: 1.32-4.04), healthier diet ( OR=2.09,95% CI: 1.45-2.96), daily intake of fresh fruit ( OR=1.67,95% CI: 1.17-2.36) and combination treatment ( OR=1.82,95% CI: 1.03-3.09) were more likely to meet intensive SBP control goal after adjustment of age, sex and urban/rural areas. During an average follow-up of (10.0±3.7) years, 1 278 cases of composite cardiovascular outcome were recorded. This study did not find a statistical correlation between achieving the goal of enhanced SBP control and the occurrence of composite cardiovascular and cerebrovascular outcomes ( HR=0.89, 95% CI: 0.63-1.25). For major adverse cardiovascular events (MACE), cerebrovascular diseases, stroke, and ischemic stroke, we observed a trend of decrease in risk of outcomes with more intensive SBP control (trend test P<0.05). Conclusions:We observed decreased risk for MACE and cerebrovascular diseases with more intensive SBP control. However, there was no significant risk reduction for cardiovascular and cerebrovascular diseases when meeting the intensive SBP control goal, compared to the standard SBP control goal.

Objective:To investigate the efficacy and safety of ixazomib combined with lenalidomide and dexamethasone (IRd) regimen in treatment of multiple myeloma (MM) patients in the real world practice.Methods:The clinical data of 24 MM patients treated with IRd regimen from January 2019 to January 2021 in the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively analyzed, and their efficacy and adverse reactions were analyzed. Among the 24 patients, 5 patients were relapsed and refractory (relapsed/refractory group), and 19 newly treated patients (conversion group) who responded to bortezomib induction therapy but converted to IRd regimen due to adverse reactions or other reasons.Results:The 24 patients were treated for a median of 4 cycles (2-7 cycles), with 8 cases of complete remission (CR), 6 cases of very good partial remission (VGPR), 8 cases of partial remission (PR), 1 case of disease progression (PD), 1 case of minimal response (MR), and the overall response rate (ORR) was 91.7% (22/24); the median progression-free survival (PFS) time was 15 months (95% CI 6.6-23.4 months); 6 CR patients were negative for minimal residual disease (MRD). The common adverse reactions were hematological adverse reactions, peripheral neuropathy, fatigue, gastrointestinal reactions, and infections. The incidence rate of grade 3-4 adverse reactions was 25.0% (6/24). In the relapsed/refractory group, the best efficacy was VGPR in 1 case, PR in 3 cases, and MR in 1 case, all patients withdrew from the IRd regimen therapy due to PD after transient remission or poor effect; in the conversion group, the best efficacy was CR in 8 cases, VGPR in 5 cases, PR in 5 cases, and PD in 1 case, 57.9% (11/19) patients maintained their original best response, and 36.8% (7/19) patients improved their best response to CR; the difference in median PFS time between the two groups was statistically significant (7 months vs. not reached, P = 0.018). Conclusions:The IRd regimen is safe and effective for MM patients, especially for the conversion patients after effective bortezomib induction therapy. Although patients with relapsed/refractory MM who have previously used multi-line therapy respond to IRd regimen, the duration of remission is limited.

Objective    To explore the mechanism of dihydrouridine synthase 4-like (DUS4L) on the development of lung adenocarcinoma (LUAD). Methods    The RNA-seq expression data of LUAD was downloaded from The Cancer Genome Atlas (TCGA), and the relationship between its clinical pathological characteristics and DUS4L mRNA expression was evaluated. The effect of DUS4L knockdown on the proliferation of A549 cells was detected by EDU proliferation assay. The gene expression profile of lung adenocarcinoma A549 cells in the DUS4L knockdown group (KD group) and control group (NC group) was detected by transcriptome sequencing technique. The differential genes were screened by DESeq2. ClusterProfiler was used to perform GO functional enrichment analysis of differential genes. Results    The expression of DUS4L mRNA in LUAD tissues was higher than that in normal tissues, and the up-regulation of DUS4L was related to the clinical pathological characteristics of LUAD patients. EDU proliferation assay suggested that knocking down DUS4L could inhibit the proliferation of A549 cells. A total of 456 differential genes were screened, including 289 up-regulated genes and 167 down-regulated genes [|log2(fold change)|>1 and Padj<0.05]. STC2 and TRIB3 were significantly down-regulated (P<0.05). Differential genes were mainly involved in the production of interleukin-8, angiogenesis, vascular endothelial cell proliferation and other biological pathways. Conclusion    DUS4L can widely regulate the gene expression of LUAD cells, which provides a new idea for further studying the function and role of DUS4L in the occurrence and development of LUAD and finding new therapeutic targets for LUAD.

BACKGROUND: Immune checkpoint inhibitor associated pneumonia (CIP) is a serious side effect of immune checkpoint inhibitors. There is a consensus on the treatment of acute phase of CIP, but the treatment of pulmonary interstitial fibrosis after the acute phase is still a clinical problem to be solved. METHODS: The diagnosis and treatment of a non-small cell lung cancer (NSCLC) patient with immune checkpoint inhibitor associated pneumonia in the Stereotactic Radiotherapy Department of Qingdao Central Hospital were retrospectively analyzed, and literatures were reviewed. RESULTS: A 70-year-old male patient was diagnosed with Poorly differentiated squamous cell carcinoma of left lung with mediastinal lymph node metastasis T3N3M0 stage IIIc, EGFR/ALK/ROS1/RAF negative, PD-L1 (22c3) immunohistochemistry negative. After the progression of first-line chemotherapy, the patient was diagnosed as immune checkpoint inhibitor associated pneumonia grade 3 during second-line monotherapy with Nivolumab. After initial high-dose glucocorticoid pulse therapy, the lung computed tomography (CT) imaging and clinical symptoms of the patients were partially relieved, and then pirfenidone (300 mg tid) was given orally for more than 11 months. During the treatment of pirfenidone, the CT imaging and clinical symptoms of the patients were significantly improved, and there were no other adverse reactions except grade 1 nausea. During this period, chemotherapy and Anlotinib was given concurrently with pirfenidone and showed good safety profile. CONCLUSIONS This case report is the first report of pirfenidone in the treatment of CIP, which provides a new idea for the clinical practice and research of CIP treatment.

Objective:To observe the effect of electroacupuncture at Baihui and Dazhui on cognitive function of vascular dementia rats and explore its possible mechanism. Methods:Male Sprague-Dawley rats were randomly divided into the sham operation group, model group and electroacupuncture group, with 10 rats in each group. Rats in the model group and the electroacupuncture group were made as vascular dementia models by carotid artery ligation of the two sides. After 2 weeks of modeling, the electroacupuncture group received electroacupuncture at Baihui and Dazhui for 4 weeks. Before and after the intervention, take the novel object recognition behavior test to detect the 1, 24 h new object preference coefficient; and use magnetic resonance spectroscopy to scan the levels of NAA/Cr and Cho/Cr neurometabolites in the hippocampus. q-PCR was used to detect the expression of caspase-3 and Bax in apoptotic cells. Immunohistochemistry was used to detect synapsin SYN expression. Results:Compared with the model group, the preference coefficient of new object of the electroacupuncture group at 1 h [(69.85 ± 11.26)% vs. (50.26 ± 8.85)%] and 24 h [(60.85 ± 11.86)% vs. (43.26 ± 10.25)%] significantly decreased ( P<0.01). The content of NAA/Cr (1.344 ± 0.149 vs. 0.892 ± 0.178) significantly increased ( P<0.01), and the content of Cho/Cr (0.661 ± 0.142 vs. 0.902 ± 0.178) in the hippocampus significantly decreased ( P<0.01). The expression of hippocampus caspase-3 (1.342 ± 0.041 vs. 2.437 ± 0.089), Bax (2.135 ± 0.083 vs. 4.358 ± 0.137) significantly decreased ( P<0.01), and the expression of SYN (0.577 ± 0.035 vs. 0.315 ± 0.025) significantly increased ( P<0.01). Conclusion:Electroacupuncture at Baihui and Dazhui can effectively improve the cognitive dysfunction of rats with vascular dementia, which may be related to the improvement of neuronal metabolites NAA, Cho content and inhibition of neuronal apoptosis and improvement of neuronal touch function.

Objective    To systematically evaluate the expression of programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in esophageal squamous cell carcinoma and its relationship with prognosis. Methods    The literature from PubMed, EMbase, The Cochrane Library, Web of Science, CNKI and Wanfang data from inception to February 22, 2020 was searched by computer. Data were extracted and the quality of literature was evaluated using RevMan 5.3 software for meta-analysis. Egger's and Begg's tests were used to evaluate publication bias, and Stata 15.1 software was used for sensitivity analysis. Results     A total of 16 articles were included, and there were 3 378 patients with esophageal squamous cell carcinoma. The methodological index for nonrandomized studies (MINORS) scores were all 12 points and above. The meta-analysis results showed that the positive expression rates of PD-1 and PD-L1 in tumor cells were 37.8% (190/504) and 41.7% (1 407/3 378), respectively. The positive expression of PD-L1 in tumor immune infiltrating cells was 41.7% (412/987). The overall survival (OS) of the tumor cell with high PD-L1 expression was lower than that with low PD-LI expression (HR=1.30, 95%CI 1.01-1.69, P=0.04). The OS of the tumor immune infiltrating cell with high PD-L1 expression was significantly higher than that with low PD-LI expression (HR=0.65, 95%CI 0.53-0.80, P<0.000 1). Conclusion    PD-L1 has a high expression rate in esophageal squamous cell carcinoma and is an important factor for the prognosis of esophageal squamous cell carcinoma.