BACKGROUND:The specific molecular mechanism of the transformation from normal healthy people to acute cervical spondylotic radiculopathy has not been clear,which needs to be further studied. OBJECTIVE:To investigate the differential expression of serum proteomics between normal healthy people and patients with acute cervical spondylotic radiculopathy,and to find and identify potential specific serum markers between them. METHODS:The serum samples of eight patients with acute cervical spondylotic radiculopathy and eight normal healthy people were collected,and the proteomic screening and analysis were performed by tandem mass tag combined with liquid chromatography-tandem mass spectrometry technology,in order to explore and identify serum proteins differentially expressed in patients with acute cervical spondylotic radiculopathy. RESULTS AND CONCLUSION:A total of 183 significantly differential proteins were screened by tandem mass tag technology,and 11 significantly differential proteins were identified(P＜0.05).Compared with normal healthy people,three differential proteins were significantly up-regulated,including human leukocyte antigen-A,secretoglobin family 1a member 1,and protein 4-hydroxyphenylpyruvate dioxygenase,and seven differential proteins were significantly down-regulated,such as immunoglobulin heavy constant gamma 3,skin factor,and myosin light chain 3,in patients with acute cervical spondylotic radiculopathy.Gene ontology enrichment analysis showed that these differential proteins participated in antigen binding,immunoglobulin receptor binding and other molecular functions.Protein-protein interaction analysis showed that among the common differential proteins between normal healthy people and patients with acute cervical spondylotic radiculopathy,HLA-A,HPD,PSMA3,DMKN,SCGB1A1,and MYL3 were located at the nodes of the functional network,and were closely related to the systems of body immunity,cellular inflammatory response,energy metabolism,and mechanical pressure.The significantly differential proteins HLA-A,HPD and MYL3 were verified by western blot,and the results were consistent with those of proteomics.To conclude,tandem mass tag combined with liquid chromatography-tandem mass spectrometry technology can be used to find the differentially expressed proteins in serum between normal healthy people and patients with acute cervical spondylotic radiculopathy.It is preliminarily believed that HLA-A,HPD and MYL3 may be specific serum markers of acute cervical spondylotic radiculopathy,providing a new direction for further research on its pathogenesis.

Objective:To explore the risk factors for the occurrence of thrombocytopenia (TCP) within 2 weeks after pediatric liver transplantation (LT) and examine the relationship between the occurrence of TCP and prognosis.Methods:From January 2021 to November 2021, clinical data were retrospectively reviewed for 162 pediatric LT recipients aged under 4 years at Organ Transplantation Center of Tianjin First Central Hospital.Based upon the lowest value of platelet count at Week 2 post-operation, they were assigned into two groups of TCP (n=90) and non-TCP (n=72). General preoperative profiles, intraoperative findings, postoperative complications, types of commonly used antibiotics, anticoagulant dosing and prognosis of two groups were compared.Univariate and multivariate analyses were utilized for examining the independent risk factors for TCP.Receiver operating characteristic (ROC) curve was plotted for examining the cut-off value of independent risk factors for diagnosing TCP.Results:Among them, 90 (55.56%) developed TCP within 2 weeks post-operation and 25(15.43%) developed TCP at Day 1 post-operation.The median preoperative platelet count was 178×10 9/L and the lowest value was 65×10 9/L at Day 3(1-4) post-operation with a declining rate of 63.5% and platelet count of recipient normalized at Day 6(4-7.25) post-operation.The results of univariate analysis showed statistically significant inter-group differences in operative duration[(574.43±80.53)min vs.(526.75±72.42)min], intraoperative blood loss[400(300, 550)ml vs.320(300, 400)ml], red blood cell transfusion[2(2, 3)U vs.2(1.5, 2.0)U], preoperative platelet count[178.5(141.75, 242.5)×10 9/L vs.257 (209.75, 357)×10 9/L], postoperative infection rate[27.8%(25/90)vs.13.9%(10/72)] and dosing rates of piperacillin sodium and tazobactam sodium[8.9%(8/90)vs.25.0%(18/72)] ( P<0.05). Multivariate Logistic regression analysis revealed statistically significant inter-group differences in operative duration( P=0.008), red blood cell transfusion( P=0.01), preoperative platelet count( P<0.01) and postoperative infection rate ( P=0.02). The results of ROC curve analysis showed that the cut-off values of operative duration, red blood cell transfusion and preoperative platelet count were 535 min, 2.75 U and 183.5×10 9/L respectively.Length of ICU stay was higher in TCP group than that in non-TCP group, and the difference was statistically significant [4(3, 5) vs.3(3, 4) day, P=0.006]. Conclusions:LT children aged under 4 years with intraoperative red blood cell transfusion>2.75 U, operative duration>535 min and preoperative platelet count<183.5×10 9/L are more likely to develop post-transplantation TCP.And occurrence of TCP prolongs the length of ICU stay in pediatric recipients.

INTRODUCTION: Ustekinumab is a human monoclonal antibody that binds to the p40 subunit of both interleukin (IL)-12 and IL-23, and it is approved for the treatment of moderate to severe plaque psoriasis. In this study, we assessed the efficacy and safety of patients receiving ustekinumab for psoriasis. METHODS: This retrospective study included all adults with chronic plaque psoriasis who were prescribed ustekinumab in a tertiary dermatologic centre between December 2009 and December 2015. Efficacy end points included a proportion of patients achieving at least 50% and 75% improvement from baseline psoriasis area and severity index (PASI) and body surface area (BSA) at Weeks 4 and 16. RESULTS: A total of 99 patients were prescribed ustekinumab; 69% of these were Chinese, followed by 15% Indians and 9% Malays. 31 patients had documented PASI scores and 55 patients had documented BSA improvements. In patients with recorded PASI scores, 29 (93.5%) of 31 patients achieved PASI 50, and 21 (67.7%) of 31 achieved PASI 75 at week 16. In patients with recorded BSA, 43 (78.2%) of 55 had at least 50% BSA improvement, and 31 (56.4%) of 55 achieved 75% BSA improvement at 16 weeks. Regarding safety, no patient experienced tuberculosis reactivation. A total of 11 (11%) of 99 patients had latent tuberculosis infection and were treated with prophylactic isoniazid. No patient experienced serious adverse events. No cardiovascular events, cutaneous malignancies or deaths were reported over six years. CONCLUSION Ustekinumab is safe and efficacious in the treatment of patients with moderate to severe plaque psoriasis in a multiethnic Asian population.
Adult ; Humans ; Ustekinumab/therapeutic use* ; Singapore ; Retrospective Studies ; Treatment Outcome ; Severity of Illness Index ; Double-Blind Method ; Psoriasis/drug therapy*

The improvement of survival of osteosarcoma patients by the standard treatment strategy of osteosarcoma(neoadjuvant chemotherapy+surgical treatment+adjuvant chemotherapy)has been stabilized in the past 20 years,and the emergence of the slow(controlled)-release drug delivery system has provided a new strategy for the treatment of osteosarcoma.At present,thanks to the development of nanotechnology,great progress had been made to the technology of slow-release chemotherapy for osteosarcoma in China,but the clinical translation of the slow-release chemotherapy system has become the key to constrain its development.Based on this,this review summarizes the preclinical research progress of the main chemotherapeutic agents for osteosarcoma,including methotrexate,doxorubicin,cisplatin,and isocyclophosphamide,in the recent years,with the expectation of clarifying the safety and efficacy of the slow-release chemotherapy system for osteosarcoma,and facilitating the clinical translation of the slow-release chemotherapy system for osteosarcoma.

Alternative polyadenylation(APA)is a crucial step in post-transcriptional regulation.Previous bioinformatic studies have mainly focused on the recognition of polyadenylation sites(PASs)in a given genomic sequence,which is a binary classification problem.Recently,computa-tional methods for predicting the usage level of alternative PASs in the same gene have been pro-posed.However,all of them cast the problem as a non-quantitative pairwise comparison task and do not take the competition among multiple PASs into account.To address this,here we propose a deep learning architecture,Deep Regulatory Code and Tools for Alternative Polyadenylation(DeeReCT-APA),to quantitatively predict the usage of all alternative PASs of a given gene.To accommodate different genes with potentially different numbers of PASs,DeeReCT-APA treats the problem as a regression task with a variable-length target.Based on a convolutional neural network-long short-term memory(CNN-LSTM)architecture,DeeReCT-APA extracts sequence features with CNN layers,uses bidirectional LSTM to explicitly model the interactions among com-peting PASs,and outputs percentage scores representing the usage levels of all PASs of a gene.In addition to the fact that only our method can quantitatively predict the usage of all the PASs within a gene,we show that our method consistently outperforms other existing methods on three different tasks for which they are trained:pairwise comparison task,highest usage prediction task,and rank-ing task.Finally,we demonstrate that our method can be used to predict the effect of genetic variations on APA patterns and sheds light on future mechanistic understanding in APA regulation.

Objective: To explore the association between single nucleotide polymorphism rs12632942 in SCN10A exon and oxaliplatin-induced peripheral neuropathy (OXLIPN) in colorectal cancer (CRC) patients receiving chemotherapy. Methods:Atotal of 319 cases of blood samples from CRC patients receiving chemotherapy regimen with Oxaliplatin (OXL) were collected from the Second Affiliated Hospital of Guangzhou Medical University, the Second Affiliated Hospital of Nanchang University, and Guangzhou Baiyun District Hospital of Chinese Medicine during January 2011 and June 2013. DNAwas routinely extracted, and PCR amplification was performed to analyze the genotype of rs12632942; and OXLIPN of patients was also evaluated. The association between rs12632942 genotype and OXLIPN was analyzed by χ2 test and multivariate logistic regression model. Results: The genotypes of rs12632942 of 319 CRC patients:AAof 134 cases,AG of 156 cases and GG of 29 cases; and the genotype distribution of rs12632942 was in accordance with Hardy-Weinberg equiliberum (P>0.05). χ2 test showed that rs12632942AG+GG genotype was associated with Ⅱ-Ⅳ degree OXLIPN (P<0.01). Multivariate logistic regression model showed that rs12632942 AG + GG genotype was an independent risk factor for Ⅱ-Ⅳ degree OXLIPN（OR=2.044； 95%CI=1.231-3.392; P<0.01） . Conclusion: Colorectal cancer patients with SCN10A exon polymorphism rs12632942AG + GG genotype were susceptible to Ⅱ-Ⅳ degree OXLIPN.

OBJECTIVETo examine the association between the genotype (LL, LS and SS) of serotonin transporter promoter gene polymorphism(5-HTTLPR) and clinicopathological factors, and to investigate the effect of 5-HTTLPR on the prognosis of colorectal cancer patients.

METHODSData of peripheral blood samples of 161 colorectal cancer patients at the Second Affiliated Hospital of Guangzhou Medical University from October 2009 to January 2014 were collected retrospectively. The genotyping of 5-HTTLPR was determined by PCR and agarose gel electrophoresis. Coincidence Chi-square test was used to examine the 5-HTTLPR genotype with Hardy-Weinberg law. Chi-square test and Cox multifactor model were used to analyze the association of 5-HTTLPR genotype with clinicopathology and prognosis. All the patients were informed and agreed to participate in the study. This study was approved by the Hospital Ethics Committee (2015056).

RESULTSOf 161 colorectal cancer patients, 89 were male and 72 were female; the median age was 64 (25-85) years; 86 (53.5%) cases were colon cancer and 75 (46.5%) were rectal cancer. Genotype was LL in 12 cases, LS in 59 cases and SS in 90 cases, which complied with the law of Hardy-Weinberg genetic balance (χ²=0.288, P=0.592). Univariate analysis showed that 5-HTTLPR gene polymorphism was only associated with lymph node metastasis [lymph node metastasis rate: LL and LS genotype 21.1% (15/71);SS genotype 40.0% (36/90), χ²= 6.532, P=0.011]. The 3-year and 5-year overall survival rates of whole patients were 71% and 63% respectively. Multivariate analysis revealed that the SS genotype was an independent risk factor affecting the overall survival of colorectal cancer patients(HR=1.933, 95%CI:1.090-3.428, P=0.024).

CONCLUSIONAmong genotypes of 5-HTTLPR gene, colorectal cancer patients with SS genotype have higher risk of lymph node metastasis and poorer prognosis.

Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; genetics ; pathology ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Prognosis ; Retrospective Studies ; Serotonin Plasma Membrane Transport Proteins ; genetics

Objective To analyze the susceptibility of serotonin promoter single nucleotide polymorphism (SNP)rs956304 to chemotherapy-induced nausea and vomiting(CINV)in colorectal cancer.Methods Rs956304 genotypes and the clinical pathological data of 166 patients with colorectal cancer from September 2009 to April 2014 were retrospectively analyzed. Rs956304 genotype was analyzed by sequencing. The correlations between rs956304 genotype,factors of clinical pathology and CINV were analyzed by chi-square test. Unconditional logistic regression model was used to analyze the independent effect of rs956304 genotype on colorectal cancer CINV. Results Chi-square test showed that moderate to severe CINV was associated with rs956304 AG+GG genotype (P=0.011). Unconditional logistic regression model showed that the patients with AG+GG genotype had a signifi-cant higher risk of moderate to severe CINV than AA genotype(OR=3.215,95% CI:1.202 to 8.599,P=0.020). Conclusion Rs956304 AG+GG genotype is an independent risk factor for moderate to severe colorectal cancer CINV.

Objective:To evaluate the irritation and hypersensitivity of Biyan black plaster with different coating process. Meth-ods:The skin irritation test was carried out on healthy New Zealand rabbits. Totally 18 rabbits were divided into 3 groups randomly, and Biyan black plaster Ⅰ, Biyan black plaster Ⅱ and Biyan black plaster Ⅲ was painted on the skin of rabbits, respectively, and blank plaster was used as the autologous negative control. Erythema and edema on the skin after the administration were evaluated and the scored. The skin hypersensitive test was carried out on health guinea pigs. Totally 50 guinea pigs were randomly divided into 5 groups:Biyan black plaster Ⅰ group, Biyan black plaster Ⅱ group, Biyan black plaster Ⅲ group, the negative control (the blank plaster) and the positive group(1% 2,4-dinitrochlorobenzene). The skin allergy at 24 h and 48 h was observed and the score was e-valuated. Results:The average score of stimulus response for Biyan black plasterⅠwas no more than 0.42 and the sensitization rate was 0,which had no differences when compared with those of the blank control group(P>0.05),suggesting no obvious irritation and sensitization. The average score of stimulus response of Biyan black plasterⅡwas no more than 0.83,which showed statistical signifi-cance when compared with that of the blank control group (P<0.05), and the sensitization rate was 10%, which had no difference when compared with that of the blank control group (P>0.05), suggesting mild irritation without obvious sensitization. The average score of stimulus response of Biyan black plasterⅢwas no more than 1.17,which showed statistical significance when compared with that of the blank control group (P<0.01),and the sensitization rate was 20%,which had no difference when compared with that of the blank control group (P>0.05),suggesting mild irritation and light sensitization. Conclusion:Biyan black plaster I without skin irritation and hypersensitivity can be externally used safely.

The processing of traditional Chinese medicine(TCM) is a traditional pharmaceutical technology,which meets the development demand of the treatment based on syndrome differentiation of TCM. It is one of the important means to guarantee the quality of Chinese medicine and improve the clinical efficacy of TCM. Medical institutions of traditional Chinese medicine should take the advantages and characteristics of traditional Chinese medicine as the foundation, vigorously carry out processing technology for traditional Chinese medicine, rich clinical drug varieties of traditional Chinese medicine, and develop such characteristics of TCM as treatment based on syndrome differentiation and individualized drug treatment. The processing of temporary prescriptions is one of the important means to reflect the characteristics of TCM, and it is of great significance to improve the curative effect of TCM. Based on working practice, this paper summarized the development current status, significance, technical standards and samples of processing variety and methods etc in order to provide thoughts for the processing technology of temporary prescriptions in medical institutions.