Objective:To study the correlation between the copy number variations of CCND1 gene and chromosome 11 and their associations with clinicopathologic features in acral melanoma.Methods:Thirty-three acral melanoma cases diagnosed at the Department of Pathology of Peking University Third Hospital, Beijing, China from January 2018 to August 2021 were collected. Fluorescence in situ hybridization (FISH) was used to detect the copy number of CCND1 gene and centromere of chromosome 11. The relationship between the copy numbers of CCND1 and chromosome 11 centromere, and the correlation between CCND1 copy number and clinicopathologic characteristics were analyzed.Results:There were 15 male and 18 female patients, with an age ranging from 22-86 years. 63.6% (21/33) of the patients had an increased CCND1 gene copy number. 21.2% (7/33) of patients with increased CCND1 copy number had an accompanying chromosome 11 centromere copy number increase. 27.3% (9/33) of the cases had a low copy number of CCND1 gene, and 4 of them (4/33, 12.1%) were accompanied by chromosome 11 centromere copy number increase. 36.4% (12/33) of the cases had a high copy number of CCND1 gene, and 3 (3/33, 9.1%) of them were accompanied by chromosome 11 centromere copy number increase. No cases with CCND1 low copy number increase showed CCND1/CEP11 ratio greater than 2.00. The 11 cases with CCND1 high copy number increase showed CCND1/CEP11 ratio greater than or equal to 2.00. However, there was no significant correlation between CCND1 copy number increase and any of the examined clinicopathologic features such as age, sex, histological type, Breslow thickness, ulcer and Clark level.Conclusions:CCND1 copy number increase is a significant molecular alteration in acral melanoma. In some cases, CCND1 copy number increase may be accompanied by the copy number increase of chromosome 11. For these cases the copy number increase in CCND1 gene may be a result of the copy number change of chromosome 11.

Ginkgo biloba preparation is widely used as natural extract preparation both domestically and internationally, for myocardial infarction and cerebral infarction diseases in China; and mainly used to improve memory and treat dementia symptoms abroad. In recent years, there have been a large amount of reports on the treatment of ophthalmic diseases, mental diseases, kidney diseases and so on, however some of which have not uniform literature result. Therefore, it is necessary to summarize the reports on off-label use of Ginkgo biloba preparation. Among them, Ginkgo biloba preparation has a lot of controversy on brain diseases such as dementia and autism, mainly due to the mild effect, the difficulty in tracking long-term medication data for chronic diseases, and the subjective evaluation results of cognitive level, so more high-level research is needed to provide data support. In addition, Ginkgo biloba preparation has obvious protective effects on peripheral nerves and microvascular, and as an adjuvant drug in related diseases, it can effectively accelerate the recovery process of patients. This article summarizes various reports on Ginkgo biloba preparations, which can better clarify the product positioning and provide a reference for the selection of relevant treatment options.

The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients. With the widespread applica-tion of ICIs in HCC, the management of immune-related adverse events (irAE) gained more and more attention. However, the complicated disease characteristics and various combination therapies in HCC throw out challenges to irAE management. Therefore, the editorial board of the 'Chinese expert consensus on the management of immune-related adverse events of hepatocellular carcinoma treated with immune checkpoint inhibitors (2021 edition)' organizes multidisciplinary experts to discuss and formulate this consensus. The consensus focuses on issues related to HCC irAE manage-ment, and puts forward suggestions, in order to improve standardized and safety clinical medication, so as to maximize the benefits of immunotherapy for patients.

Objective: To describe and compare the epidemiology of Sepsis-1 and Sepsis-3 in Yuetan Subdistrict of Beijing, and to estimate the incidence of Sepsis-3 in China. Methods: A population-based cohort study was conducted. Through the database of Beijing Public Health Information System, the medical records of all adult residents hospitalized from July 1st, 2012 to June 30th, 2014 in Yuetan Subdistrict were reviewed. According to the clinical data of these patients, patients with Sepsis-1 and Sepsis-3 were enrolled in this analysis and the demographic characteristics of them were compared. Incidence and in-hospital mortality was calculated. Logistic regression method was used to analyze the risk factors of sepsis. Results: Compared with non-septic patients with infections, patients with Sepsis-1 or Sepsis-3 were more likely to be male, older, had more comorbidities and lower body mass index (BMI), had more lower respiratory tract infections, more intra-abdominal infections and more blood flow infections, but had fewer urogenital tract infections, fewer upper respiratory tract infections, fewer gastrointestinal infections and fewer skin and soft tissue infections, and had pure prognosis with longer length of hospital stay [days, Sepsis-1 compared with non-Sepsis-1: 18 (10, 34) vs. 14 (9, 22), Sepsis-3 compared with non-Sepsis-3: 20 (11, 39) vs. 14 (9, 25)] and higher mortality [Sepsis-1 compared with non-Sepsis-1: 20.6% (353/1 716) vs. 2.5% (44/1 733), Sepsis-3 compared with non-Sepsis-3: 32.0% (299/935) vs. 3.9% (98/2 514), all P < 0.01]. Logistic regression analysis showed that male, elder (age ≥ 65 years old), low BMI, bed-rest state, and combined with cerebrovascular disease and hematological malignancies were risk factors for Sepsis-1 [all odds ratio (OR) > 1, all P < 0.05], while the male, elder (age ≥ 65 years old), low BMI, bed-rest state, and combined with cerebrovascular disease, rheumatic immune disease, malignant diseases of blood system and dementia were risk factors for Sepsis-3 (all OR > 1, all P < 0.05). Sepsis-3 was more common in males [OR = 1.19, 95% confidence interval (95%CI) was 1.01-1.40, P < 0.05] and elderly patients (age 65-84 years old: OR = 1.60, 95%CI was 1.28-1.99, P < 0.01; age ≥ 85 years old: OR = 1.76, 95%CI was 1.39-2.23, P < 0.01) as compared with Sepsis-1. After adjusted for gender and age, the standardized incidence of Sepsis-1 was 461 per 100 000 person-year, and that of Sepsis-3 was 236 per 100 000 person-year, with the standardized mortality of 79 per 100 000 person-year and 67 per 100 000 person-year, respectively, in Yuetan Subdistrict of Beijing. Corresponding to a speculative extrapolation of 4 856 532 new cases for Sepsis-1 and 2 487 949 new cases for Sepsis-3, there were 831 674 deaths and 700 437 deaths per year in China, respectively. Conclusions Male, elder, more comorbidities and low BMI were risk factors for sepsis. The standardized incidence of Sepsis-3 in Yuetan Subdistrict of Beijing was 236 per 100 000 person-year, and speculated there were 2.5 million new cases of Sepsis-3 per year, resulting in more than 700 000 deaths in China. According to the diagnostic criterion of Sepsis-3, 2.36 million new cases per year were reduced, and the mortality was increased by 11.4%, as compared with the criterion of Sepsis-1.

OBJECTIVE: To describe and compare the epidemiology of Sepsis-1 and Sepsis-3 in Yuetan Subdistrict of Beijing, and to estimate the incidence of Sepsis-3 in China. METHODS: A population-based cohort study was conducted. Through the database of Beijing Public Health Information System, the medical records of all adult residents hospitalized from July 1st, 2012 to June 30th, 2014 in Yuetan Subdistrict were reviewed. According to the clinical data of these patients, patients with Sepsis-1 and Sepsis-3 were enrolled in this analysis and the demographic characteristics of them were compared. Incidence and in-hospital mortality was calculated. Logistic regression method was used to analyze the risk factors of sepsis. RESULTS: Compared with non-septic patients with infections, patients with Sepsis-1 or Sepsis-3 were more likely to be male, older, had more comorbidities and lower body mass index (BMI), had more lower respiratory tract infections, more intra-abdominal infections and more blood flow infections, but had fewer urogenital tract infections, fewer upper respiratory tract infections, fewer gastrointestinal infections and fewer skin and soft tissue infections, and had pure prognosis with longer length of hospital stay [days, Sepsis-1 compared with non-Sepsis-1: 18 (10, 34) vs. 14 (9, 22), Sepsis-3 compared with non-Sepsis-3: 20 (11, 39) vs. 14 (9, 25)] and higher mortality [Sepsis-1 compared with non-Sepsis-1: 20.6% (353/1 716) vs. 2.5% (44/1 733), Sepsis-3 compared with non-Sepsis-3: 32.0% (299/935) vs. 3.9% (98/2 514), all P < 0.01]. Logistic regression analysis showed that male, elder (age ≥ 65 years old), low BMI, bed-rest state, and combined with cerebrovascular disease and hematological malignancies were risk factors for Sepsis-1 [all odds ratio (OR) > 1, all P < 0.05], while the male, elder (age ≥ 65 years old), low BMI, bed-rest state, and combined with cerebrovascular disease, rheumatic immune disease, malignant diseases of blood system and dementia were risk factors for Sepsis-3 (all OR > 1, all P < 0.05). Sepsis-3 was more common in males [OR = 1.19, 95% confidence interval (95%CI) was 1.01-1.40, P < 0.05] and elderly patients (age 65-84 years old: OR = 1.60, 95%CI was 1.28-1.99, P < 0.01; age ≥ 85 years old: OR = 1.76, 95%CI was 1.39-2.23, P < 0.01) as compared with Sepsis-1. After adjusted for gender and age, the standardized incidence of Sepsis-1 was 461 per 100 000 person-year, and that of Sepsis-3 was 236 per 100 000 person-year, with the standardized mortality of 79 per 100 000 person-year and 67 per 100 000 person-year, respectively, in Yuetan Subdistrict of Beijing. Corresponding to a speculative extrapolation of 4 856 532 new cases for Sepsis-1 and 2 487 949 new cases for Sepsis-3, there were 831 674 deaths and 700 437 deaths per year in China, respectively. CONCLUSIONS Male, elder, more comorbidities and low BMI were risk factors for sepsis. The standardized incidence of Sepsis-3 in Yuetan Subdistrict of Beijing was 236 per 100 000 person-year, and speculated there were 2.5 million new cases of Sepsis-3 per year, resulting in more than 700 000 deaths in China. According to the diagnostic criterion of Sepsis-3, 2.36 million new cases per year were reduced, and the mortality was increased by 11.4%, as compared with the criterion of Sepsis-1.
Adult ; Aged ; Aged, 80 and over ; Beijing/epidemiology* ; China ; Cohort Studies ; Health Information Systems ; Humans ; Male ; Retrospective Studies ; Sepsis/epidemiology*

Abtract: Acute coronary syndrome is a common clinical and frequently occurring disease, belonging to the chest discomfort, heartache, and true heart pain of TCM category. The clinical observation shows that the heat and blood stasis, and poison damage heart nutrient is one of the important mechanisms of triggering coronary syndrome. Therefore, the method of promoting blood circulation to remove meridian obstruction and the Qing Ying detoxication was established as the basic treatment, and Danshen Tongluo Jiedu Decoction is applied as the main formula. According to the different types of disease and syndrome differentiation, flexible modification can achieve good efficacy. It is expected that these will provide new ideas and methods for clinical treatment of acute coronary syndrome.

Objective To explore the effects ofDanshen Tongluo Detoxication Decoction on the inflammatory response of rats with bone marrow stem cell (BMSC) transplantation in acute myocardial infarction (AMI); To discuss its mechanism of action.Methods The whole bone marrow adherent method was adopted for BMSCs separation and culture. The AMI model was established by closing the left anterior descending coronary artery of SD rats. After the modeling, SD rats were randomly divided into sham-operation group, model group and BMSCs group (BMSCs transplantation group),Danshen Tongluo Detoxication Decoction group, Danshen Tongluo Detoxication Decoction + BMSCs group, 10 rats in each group. BMSCs cell suspension was injected directly into the edge of the myocardial tissue infarction area; Chinese medicine or normal saline were administered for gavage. 4 weeks later, the contents of MCP-1 and sICAM-1 in each group were detected by ELISA. TLR-4 expression was measured by Western blot method, and HE staining was used to observe the myocardial tissue pathological changes.Results Compared with the model group, the contents of MCP-1 and sICAM-1 and the protein expression of TLR-4 in BMSCs group,Danshen Tongluo Detoxication Decoction group, andDanshen Tongluo Detoxication Decoction + BMSCs group decreased, Danshen Tongluo Detoxication Decoction group was better than BMSCs group (P<0.05,P<0.01), andDanshen Tongluo Detoxication Decoction + BMSCs group was better than BMSCs group andDanshen Tongluo Detoxication Decoction group(P<0.05,P<0.01).Conclusion BMSCs transplantation combined withDanshen Tongluo Detoxication Decoction can restrain the inflammatory response of AMI model rats and repair ischemic myocardium issue, which mechanism may be related to regulating TLR-4 induced inflammatory response.

Objective To investigate the effects of soothing liver and activating blood Chinese medicine on myocardial cell apoptosis and related gene expression of BMSCs transplanting on myocardial ischemia reperfusion injury (IRI) of rats;To discuss its mechanism of protecting myocardium. Methods Model of myocardial IRI was established in rats. BMSCs were isolated, cultivated, and transplanted in IRI rats. SD rats were randomly divided into sham-operation group, IRI group, BMSCs group, and combined group. Rats in combined group received gavage with soothing liver and activating blood Chinese medicine, while rats in other groups received gavage with the same dose of normal saline. After 4 weeks, myocardial cell apoptosis, Bcl-2, and Bax protein expression in myocardial cells were detected by TUNEL method and immunohistochemical method. Results Compared with IRI group, myocardial cell apoptosis index in the combined group and BMSCs group was lower, Bax expression decreased, Bcl-2 expression significantly increased (P<0.01);Compared with BMSCs group, myocardial cell apoptosis index in the combined group was lower;Bax expression decreased, Bcl-2 expression increased (P<0.05, P<0.01). Conclusion Soothing liver and activating blood Chinese medicine can inhibit BMSCs transplantation in IRI rat myocardial cell apoptosis, promote myocardial regeneration, and protect myocardial cells.

Objective To investigate the effect of shRNA-mediated down-regulation of the receptor for activated C kinase 1 (RACK1) gene on the chemotherapeutic sensitivities in human lung adenocarcinoma cell line A549.Methods The shRNA recombinant plasmid targeting to human RACK1 gene was designed and transferred into A549 cells by lipofectin technique.The protein level of RACK1 was measured by Western blot to confirm the function of shRNA plasmid.Drug sensitivities of A549 cells to cisplatin,gemcitabine,pemetrexed and paclitaxel were analyzed by MTT assay.The protein expression of LRP and MRP were detected by Western blot.Results After 24 hours transfection,the relative expression quantity of RACK1 protein in RACK1-shRNA group was 0.267± 0.470,which was significantly lower than that in vector-shRNA group (0.821±0.109) and control group (0.842±0.060) (F =54.438,P ＜ 0.05).The results of MTT showed that the growth of A549 cells in the RACK1-shRNA group was markedly inhibited.The sensitivities of A549 cells to cisplatin and paclitaxel were significantly enhanced compared with that in the vector-shRNA group and control group (P ＜ 0.05).The relative expression quantity of LRP and MRP protein in RACK1-shRNA group were 0.163±0.056 and 0.246±0.050,which were lower than that in vector-shRNA group and control group (F LRP =19.430,F MRP =61.548,both P ＜ 0.05).Conclusion Targeted gene silencing of RACK1 improves the sensitivity of A549 cells to the ascisplatin and paclitaxel medicines,which might be achieved through down-regulation of the expression of LRP and MRP.

OBJECTIVETo identify mutations of dystrophin gene in a Chinese pedigree affected with Duchenne muscular dystrophy (DMD).

METHODSClinical data from the pedigree was collected. Subsequently, polymerase chain reaction and DNA sequencing analysis were applied to detect the potential mutations. Restriction enzyme digestion was carried out to determine whether the mutation was present in 118 healthy controls. Clustal software was applied for analyzing the conservation of altered amino acids.

RESULTSDNA sequencing analysis has identified a heterozygous missense mutation c.7578G>C (p.Gln2526His) mutation in exon 52 of the dystrophin gene in the proband and his mother. The same mutation was absent in the 118 healthy controls. Restriction enzyme digestion has confirmed above result. Clustal analysis indicated that the altered amino acid is highly conserved in mammals.

CONCLUSIONThe results revealed a novel missense mutation (c.7578G>C) of the dystrophin gene in DMD patients.

Adolescent ; Adult ; Amino Acid Sequence ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Case-Control Studies ; Child ; Child, Preschool ; China ; Dystrophin ; genetics ; Exons ; Female ; Humans ; Male ; Molecular Sequence Data ; Muscular Dystrophy, Duchenne ; genetics ; Mutation, Missense ; Pedigree ; Young Adult