Brain ; Head

Dysregulation of histone deacetylases (HDACs) is closely related to tumor development and progression. As promising anticancer targets, HDACs have gained a great deal of research interests and two decades of effort has led to the approval of five HDAC inhibitors (HDACis). However, currently traditional HDACis, although effective in approved indications, exhibit severe off-target toxicities and low sensitivities against solid tumors, which have urged the development of next-generation of HDACi. This review investigates the biological functions of HDACs, the roles of HDACs in oncogenesis, the structural features of different HDAC isoforms, isoform-selective inhibitors, combination therapies, multitarget agents and HDAC PROTACs. We hope these data could inspire readers with new ideas to develop novel HDACi with good isoform selectivity, efficient anticancer effect, attenuated adverse effect and reduced drug resistance.

Objective:To investigate the relationship between the dose of preoperative neoadjuvant radiotherapy and the pathologic complete response (pCR) rate in patients with locally advanced squamous cell esophageal cancer (ESCC).Methods:Clinical data of 116 patients with ESCC who received neoadjuvant chemoradiotherapy followed by esophagectomy in our cancer center from July 2017 to December 2019 were retrospectively analyzed. The radiation doses were divided into 2 ranges based on Grays (Gy) received: 40-45 Gy and 45 Gy or more.Results:The overall pCR rate was 38. 8%(45/116). pCR was observed in 35 out of 80(44%) patients treated with 40-45 Gy and 10 of 36(28%) patients treated with 45 Gy or more. The pCR rate did not significantly differ between two groups [(40-45 Gy) vs.( ≥ 45 Gy), P=0.105)]. Conclusions:Preoperative neoadjuvant radiotherapy with a higher dose (≥ 45 Gy) fails to increase the pCR rate in patients with locally advanced ESCC. Prospective randomized trials are required to determine the optimal dose of preoperative adjuvant radiotherapy.

Objective: To investigate the current status and influencing factors of geriatric nursing competence of clinical nurses from grade A tertiary hospitals in Guangdong Province, and provide basic materials and evidence-based reference for the set of suitable allocation of geriatric nursing competence training plan. Methods: By convenience sampling, a total of 2 067 clinical nurses from 40 grade A tertiary hospitals in 16 prefecture-level cities in Guangdong Province were investigated with general information questionnaire and self-made geriatric nursing competence scale for clinical nurses. Results: The item average score was 2.30±0.71. Among three domains, professional literacy scored the highest, followed by professional practice and professional development. Among ten sub-domains, the top three scored were law and ethic, critical thinking and safe management while the bottom three were coaching and mentoring, professional learning, research and innovation. Multiple linear regression showed that the influencing factors of geriatric nursing competence were nursing age (B=0.011, 95%CI 0.006-0.015, P<0.01), professional title (B=0.031, 95%CI 0.002-0.066, P<0.05), interest in aged care (B=0.214, 95%CI0.179-0.250, P<0.01) and experience regarding geriatric specialized or professional nurses qualification training(B=0.250, 95%CI 0.152-0.349, P<0.01). Conclusions The geriatric nursing competence of clinical nurses from grade A tertiary hospital in Guangdong Province is in the middle level. Interventions to improve the professional development competence of clinical nurses is thus much needed. Hospital managers should establish the talent team according to geriatric nursing competence of clinical nurses, and take related training.

Objective To detect serum level of long noncoding RNA ( lncRNA) BC200 in gastric cancer(GC) patients, and investigate its relationship with clinical features , and evaluate its diagnostic value for GC.Methods A case-control study was performed.From November 2014 to July 2015, serum levels of lncRNA BC200 were detected by real-time quantitative polymerase chain reaction in 124 patients with GC , 41 patients with atrophic gastritis and 59 normal controls who were hospitalized in Qilu Hospital of Shandong University.Meanwhile , serum carcinoembryonic antigen ( CEA ) and carbohydrate antigen 72-4 ( CA72-4 ) were detected by electrochemical luminescence immunoassay .Serum levels of lncRNA BC200, before and 3, 7, 10, 30, 100 days after radical operation in another 31 patients with GC were determined.The sensitivity and specificity of serum lncRNA BC200, CEA and CA72-4 were analyzed by using of the receiver operating characteristic ( ROC) curve.The comparison between two groups was performed with Mann-Whitney U test and the comparison among many groups was conducted with Kruskal-Wallis H test.Results Serum levels of lncRNA BC200 in GC patients with stage Ⅰ and Ⅱ[1.041(0.794,1.462)] and stage Ⅲ and Ⅳ[1.290 (0.978,1.794)]were significantly higher than those in patients with precancerous lesion [0.969(0.699, 1.219)]and normal controls[0.801(0.556,1.599)](H =54.68,P<0.000 1).Compared with pre-operation[1.120 (0.859,1.663)], the serum BC200 levels decreased significantly in 10 days [0.903 (0.724,1.182)](U=55.0,P<0.000 1), 30 days[0.759(0.671,1.037)](U=299.0,P=0.026 1), and 100 days[0.478(0.378,0.635)](U=41.0,P<0.000 1) after surgery.The area under the receiver operating characteristics curve ( AUC) of serum lncRNA BC200 was 0.865 for GC diagnosis, which was significantly higher than that of serum CA 72-4 ( AUC =0.699 ) or CEA ( AUC =0.807 ) .The AUC of combined detection of three tests was 0.934.Conclusion Serum lncRNA BC200 levels are significantly increased in GC patients , which may be used as a potential biomarker in GC diagnosis and monitoring .

Aim To investigate whether Hcy influenced the intestinal mucosal permeability by regulating MEK-ERK-MLCK pathway. Methods SD rats were divided into 4 groups:normal group, normal+Hcy group, TN-BS/ethanol group, TNBS/ethanol+Hcy group. Experi-mental colitis model with hyperhomocystinemia was es-tablished in rats with intracolonic administration of TN-BS and subcutaneous injection of Hcy. The colonic mucosal tissue was collected for histopathological exam-ination and activity of myeloperoxidase ( MPO ) . The protein expression of MLCK, p-MLCK, MEK, ERK and p-ERK in intestinal mucosal tissues was examined by Western blot method. The mRNA expression of ML-CK was examined by RT-qPCR method. Result Com-pared with the normal group and TNBS group, the DAI and HI scores and the MPO activity were increased in TNBS/ethanol+Hcy group ( P <0. 01 ) . Western blot and RT-qPCR showed that expression of MLCK, p-ML-CK, MEK, ERK and p-ERK increased in small intes-tine in TNBS/ethanol+Hcy group. Conclusion Hcy can increase intestinal permeability in TNBS-induced colitis rats by regulating the expression of MEK-ERK-MLCK signal pathway.

Objective To investigate the diagnostic value of PIgP/SC in diagnosis of primary hepatic cancer.Methods 58 patients with primary hepatic cancer,60 patients with liver cirrhosis and 60 healthy volunteers were studied.4 ml fasting venous blood was collected from all subjects.Serum level of AFP was detected with electrochemical chemiluminescence immunoassay system and plasma PIgR/SC level was detected by ELISA method.The level of PIgR/SC and AFP was detected at one week after surgical resection in patients with hepatic cancer.Results The levels of AFP and PIgR/SC in the three groups were significantly different (P＜0.01),and PIgR/SC was higher than that in patients with cirrhosis and volunteers (P＜0.01).There was no significant difference between patients with liver cirrhosis and liver cirrhosis(P＞0.05).AFP was higher in patients with HCC than patients with cirrhosis and volunteers.AFP was higher in patients with cirrhosis than volunteers,and the difference was statistically significant(P＜0.01).Sensitivity of PIgR/SC and AFP was 89.3％ and 54.8％,specificity was 84.6％ and 91％,Youden index was 0.751 and 0.458,AUC was 0.920 and 0.761,respectively.There was significant difference in AUC (Z=3.251,P＜0.05) of the two detection indexes for detection of primary hepatic cancer.Conclusion The value of PIgR/SC in diagnosis of primary liver cancer may by higher than that of AFP.

OBJECTIVETo identify pathogenic mutation of the TSC1 and TSC2 genes in a patient with tuberous sclerosis.

METHODSPeripheral venous blood samples and clinical data of a pregnant woman with tuberous sclerosis and 4 family members (parents, uncle and husband) were collected. Genomic DNA was extracted. All coding exons of the TSC1 and TSC2 genes and their flanking intronic sequences were amplified by polymerase chain reaction and subjected to direct sequencing.

RESULTSThe patient has presented facial angiofibroma and prefrons fibrous plaque for 20 years, and lumbar connective tissue nevus for 10 years. She also had mental retardation but no epilepsy. A novel frame-shift mutation c.4258-4261delTCAG was detected in exon 34 of the TSC2 gene, which had led to a premature stop codon TAG after the 55th amino acids. The same mutation was not found in the unaffected family members and 100 unrelated healthy controls.

CONCLUSIONThe novel frame-shifting mutation c.4258-4261delTCAG (p.Ser1420GlyfsX55) in the TSC2 gene may be responsible for the disease in the patient.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; DNA Mutational Analysis ; Female ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Pedigree ; Pregnancy ; Tuberous Sclerosis ; genetics ; Tumor Suppressor Proteins ; genetics ; Young Adult

Acupuncture Therapy ; methods ; Adult ; Female ; Humans ; Jaw ; physiopathology ; Male ; Middle Aged ; Temporomandibular Joint Disorders ; physiopathology ; therapy ; Young Adult

Objective To observe the clinical efficacy of superficial needling in treating temporomandibular joint disorder. Method Sixty patients with temporomandibular joint disorder were randomized into a treatment group and a control group, 30 in each group. The treatment group was intervened by superficial needling, and the patients were asked to repeatedly open and close mouth after the treatment; the control group was intervened by regular acupuncture. The treatment was given once a day, 10 d as a treatment course. The clinical efficacies were compared after 2 treatment courses.Result After the first treatment course, the total effective rate was 89.7% in the treatment group versus 86.2% in the control group; after the second course, the total effective rate was 96.6% in the treatment group versus 93.1% in the control group. There was a significant difference in comparing the therapeutic efficacy between the two groups after the second course (P<0.05). The relapse rate was 5.0% in the treatment group versus 33.3% in the control group, and the difference was statistically significant (P<0.05).Conclusion Superficial needling is an effective method in treating temporomandibular joint disorder.