Purpose To analyze the impact of clinicopatho-logical factors on residual tumor burden(RCB)grading system and Miller-Payne(MP)grading system in non-specific invasive breast cancer patients after neoadjuvant chemotherapy,and to explore the predictive value of the two grading systems for patient survival.Methods The clinical data of 177 patients with non-specific invasive breast cancer diagnosed by preoperative punc-ture and treated with neoadjuvant chemotherapy were retrospec-tively analyzed.The relationship of RCB grading system or MP grading system with disease free survival(DFS)and overall sur-vival(OS)was studied,and the value of the two systems in predicting prognosis was analyzed and compared.Results RCB grading was related to menstrual status,histological grading be-fore treatment,and lymph node metastasis after treatment;MP grading was related to pre-treatment histological grading,post-treatment lymph node metastasis,and pre-treatment molecular typing.By evaluating the ROC curve of recurrence and survival and comparing the area under curve(AUC),it was shown that RCB grading system was superior to MP grading system in pre-dicting recurrence and evaluating survival.Univariate and multi-variate survival analysis showed that pre-treatment clinical stag-ing,post-treatment lymph node metastasis,and RCB grading were independent factors for DFS.Pre-treatment clinical stag-ing,pre-treatment molecular typing,and RCB grading were in-dependent factors for OS,while MP grading was not an inde-pendent factor for DFS and OS.Conclusion RCB grading sys-tem has a higher predictive value for patient survival than MP grading system.RCB grading evaluation system is recommended as evaluation system for non-specific invasive breast cancer after neoadjuvant chemotherapy.

Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.

Objective: To explore the correlation of age at menarche and prehypertension in female college students. Methods: Age at menarche of 558 female college students was collected, while blood pressure, height and weight were measured, and body mass index(BMI) was calculated. Results: Average age at menarche was (12.48±0.95) years, prevalence of prehypertension was 17.56% (98/558). The age of menarche was 8-11, 12, 13, 14, 15-19, and the prevalence of hypertension was 30.95%, 10.00% , 17.31%, 10.81%, 31.58% respectively, U shape association was observed in the association between prehypertension with age at menarche, lowest when age at menarche was <12 years. There was no significant difference in prehypertension between age at menarche was 13, 14 years old with 12-year-old group, those age at menarche 8-11 or 15-19 had a significantly higher risk of developing prehypertension than those 12-year-old( OR =4.03, 4.15, P <0.05). Conclusion Early or late menarche is associated with high blood pressure, appropriate intervention for girls with early menarche and obesity may be beneficial in reducing their future hypertension.

Objective:To report the clinical manifestations and total exon detection results of one case of MYSM1 gene complex heterozygosity mutation of bone marrow failure syndrome 4 and the results of total exon detection of her family to provide a case phenotype for the early diagnosis of bone marrow failure syndrome 4.Methods:A 1-month-old girl with severe anemia was sequenced with trio-WES. Similarly, the family was also sequenced with tribe-WES to confirm the molecular diagnosis. BWA, GATK, and other software were used for annotation analysis of sequencing results. After polymerase chain reaction, Sanger sequencing was performed by ABI3730 sequencer to verify the target sequence. Moreover, the verification results were obtained by the sequence analysis software. The clinical diagnosis of this girl was reported and the relevant pieces of literature were reviewed.Results:The girl presented with pancytopenia, polydactylism, nonspecific white matter changes, and cysts. However, CD3 -CD19 + B decreased. The child was identified with MYSM1 complex heterozygous mutation by whole-exome sequencing, NM_001085487.2:c.1607_c.1611delAAGAG and c.1432C>T, which was respectively inherited from his parents. Genealogy verification confirmed that the c.1432C>T mutation carried by the father was from the grandfather (father's father) , whereas the c.1607_c.1611delAAGAG mutation carried by the mother was from the grandfather (mother's father) , whereas the grandmothers, aunts, and uncle did not carry the mutation. The child was diagnosed with BMFS4 combined with clinical phenotypic and molecular genetic findings. Conclusion:This case provides a case phenotype for the early diagnosis of BMFS4 and extends the pathogenicity variation and phenotype spectrum of the MYSM1 gene. The newly discovered pathogenic variant of MYSM1 c. 1607_c.1611delAAGAG has not been reported at home or abroad.

Objective:To investigate the clinical efficacy of neoadjuvant chemotherapy for the resectable locally advanced adenocarcinoma at the gastroesophageal junction.Methods:A retrospective cohort study was conducted to analyze 86 patients with resectable locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma at the gastroesophageal junction (T 3-4N +M 0) who were admitted to the Panzhihua Central Hospital of Sichuan Province from January 2013 to January 2016. All the patients were divided into the neoadjuvant chemotherapy group [preoperative XELOX regimen (oxaliplatin + capecitabine) adjuvant chemotherapy + surgery + postoperative XELOX regimen adjuvant chemotherapy, 46 cases] and non-neoadjuvant chemotherapy group (surgery + postoperative XELOX regimen adjuvant chemotherapy, 40 cases) according to whether neoadjuvant chemotherapy was performed before surgery. The total gastrectomy + Roux-en-Y esophagojejunostomy + D 2 lymphadenectomy or proximal subtotal gastrectomy + esophageal gastric remnant anastomosis + D 2 lymphadenectomy were applied to patients by the same team of doctors. The observation indicators included treatment situations, results of postoperative pathological examination and prognosis in the two groups. Results:In the neoadjuvant chemotherapy group, 25 patients (54.3%) had partial remission (PR), 21 patients (45.7%) had stable disease (SD), the clinical response rate was 54.3% (25/46), tumor control rate was 100.0% (46/46), and clinical stage reduction rate was 37.0% (17/46). Compared with the non-neoadjuvant chemotherapy group, the neoadjuvant chemotherapy group had a higher R 0 resection rate [100.0% (46/46) vs. 80.0% (32/40), χ2 = 4.024, P = 0.045], and in the neoadjuvant chemotherapy group, the pathological complete remission [tumor regression grade (TRG) 0] rate was 13.0% (6/46), and the overall pathological response (TRG 1 + TRG 0) rate was 56.5% (26/46). The postoperative pathological examination showed that the neoadjuvant chemotherapy group and the non-neoadjuvant chemotherapy group had statistically significant differences in the longest tumor diameter, vessel carcinoma embolus, perineural invasion, and pathological TNM staging (all P < 0.05). However, there was no statistical difference in the total humber of lymph nodes, the number of positive lymph nodes, pathological T stage, N stage, and human epidermal growth factor receptor 2 (HER2) expression in specimens (all P > 0.05). In the neoadjuvant chemotherapy group, 6 patients had grade 3 adverse reactions, and chemotherapy was suspended or the dose was adjusted. Adverse reactions in the blood system included the red blood cells reduction, white blood cells reduction and thrombocytopenia. Other adverse reactions included nausea, vomiting, and decreased appetite. There were no deaths related to radiotherapy. In the neoadjuvant chemotherapy group, the median tumor-free survival time was 20 months (5-36 months), and the 1-year and 3-year tumor-free survival rates were 89.5% and 52.4%, respectively; the median postoperative overall survival time was 20 months (9-36 months), and the 1-year and 3-year overall survival rates were 91.0% and 48.0%, respectively; 12 patients had tumor recurrence. In the non-neoadjuvant chemotherapy group, the median tumor-free survival time was 19 months (10-35 months), and the 1-year and 3-year tumor-free survival rates were 87.3% and 30.0%, respectively. The median postoperative overall survival time was 20 months (10-35 months), the 1-year and 3-year overall survival rates were 87.0% and 18.6%, respectively; 14 patients had tumor recurrence. There was a statistical difference in the tumor-free survival between the two groups ( χ2 = 4.522, P = 0.03), and there was no statistical difference in the overall survival between the two groups ( χ2 = 3.717, P > 0.05). Conclusions:XELOX regimen neoadjuvant chemotherapy is safe and effective for patients with resectable locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma at the gastroesophageal junction. It can decrease the tumor clinical stage and increase the R 0 resection rate and tumor-free survival rate.

ABSTRACT:Objective To establish a rapid molecular method for the detection of aldehyde dehydrogenase-2 (ALDH2)and investigate the gene polymorphisms of ALDH2?2 and determine whether the polymorphic ALDH2 gene is associated with drinking behavior in a Chinese population.Methods The gene polymorphisms of ALDH2?2 were detected using pyrosequencing,TaqMan Real-time PCR and GeneChip microarray technologies;genotyping of 302 volunteers was performed to assess their genetic associations with alcohol use behavior.Results We developed pyrosequencing,TaqMan Real-time PCR and GeneChip microarray methods to identify ALDH2? 2 polymorphisms.The allele frequency of ALDH2?2 was 20.36% in the Chinese population:16.33% in the alcoholic group and 27.83% in non-drinkers (P=0.001).In contrast,the genotype frequency of heterozygous ALDH2?1/?2 plus homozygous ALDH2?2/?2 was 45.28% in non-drinkers and 32.65% in the alcoholics group (P=0.030). Allele frequency of ALDH2 genotypes differed significantly between our Chinese sample and other ethnic groups in Asia,and it was significantly higher than that in European and American countries.Conclusion The developed pyrosequencing,TaqMan Real-time PCR and GeneChip microarray methods are rapid,accurate,high-throughput, convenient,and reliable for detecting ALDH2 polymorphisms.ALDH2?2 gene can protect against the development of alcoholism.The allele frequency of ALDH2 in this Chinese population differs from that in other ethnic groups.

OBJECTIVE:To explore basic technology for synthesis of active ingredients of Ophiocordyceps xuefengensis,and provide necessary technical support for comprehensive development of O. xuefengensis sourse. METHODS:Submerged fermenta-tion method was used to cultivate the mycelium,achieving efficient synthesis of active ingredients by controlling medium composi-tion and cultivation conditions. Using the bacteria as starting strain,the effects of different carbon sources (sucrose,glucose and soluble starch),different nitrogen sources (peptone,yeast extract powder,yeast extract,sodium nitrate,potassium nitrate and urea),different vitamin B(vitamin B1 and vitamin B complex)and different initial pH(pH was set at 4,5,6,7,8 and 9,re-spectively)on mycelial growth,extracellular and intracellular polysaccharide synthesis,cordycepin synthesis and intracellular triter-penoid synthesis were investigated to screen the optimal medium composition. RESULTS:The optimal carbon source,nitrogen source,vitamin B and initial pH were sucrose,yeast extract powder,vitamin B1 and 8,respectively. High biomass and metabolite accumulation levels can be obtained when carbon source was sucrose,nitrogen source was yeast extract powder,adding 0.1 g/L vi-tamin B1 with initial pH of 8. CONCLUSIONS:O. xuefengensis can efficiently accumulate metabolites,and achieve the optimiza-tion of strain cell growth and synthesis of active metabolite by optimizing and controlling the fermentation process.

Aim To investigate the effect of ASIC1 a ( acid-sensing ion channel 1 a ) on the pathological change of diabetes complication liver fibrosis and the proliferation and activation of hepatic stellate cell ( HSC-T6 ) stimulated by PDGF-BB under hyperglyce-mia. Methods Diabetes rats model was established by streptozotocin ( STZ) , and liver fibrosis rats model was induced by carbon tetrachloride ( CCl4 ) . Then, the liver extent of damage and the expression of ASIC1 a were observed in the diabetic rats, liver fibrosis rats and diabetes complication liver fibrosis rats. In vitro, after pretreated with amiloride, HSC-T6 was treated with high glucose for 24 h and then stimulated with PDGF-BB for another 24 h. The proliferation and acti-vation of HSC-T6 were observed, and the expression of ASIC1a, α-SMA and collagen Ⅰ were detected by Western blot. Results Compared with the control group, rats from diabetic group induced by STZ, liver fibrosis group induced by CCl4 , and the diabetes com-plication liver fibrosis rats co-induced by STZ and CCl4 were all observed with liver damage at different levels, and tissue injury of complication group was most seri-ous. However, the expression of ASIC1a in the three model groups was significantly increased compared to the control group. ASIC1a level was most obvious in the diabetes complication liver fibrosis rats. Amiloride pretreatment significantly decreased ASIC1 a expression and inhibited PDGF-BB mediated proliferation and the expression ofα-SMA and collagenⅠin HSC-T6 under high glucose environment. Conclusion High ambient glucose aggravates HSC activation and hepatic fibrosis, and this may be related with the increasing expression of ASIC1a.

OBJECTIVE: To explore the efficacy of individualized subcutaneous immunotherapy (SCIT) in allergic rhinitis(AR) maintain phase. METHOD: Compare nasal symptom scores (VAS) and special disease scale--nasal conjunctivitis quality of life questionnaire(RQLQ) score after 3 years treatment to evaluate the therapeutic effect of each group and the level of improving patients quality of life. Take patients' blood to detect the serum level of IL-10 by enzyme linked immunosorbent test (enzyme linked immunosorbent assay). RESULT: After 3 years treatment, there was no difference of VAS between the conventional SCIT group and the individualized SCIT group. ELISA results showed that the level of IL-10 was significantly higher in the drug symptomatic treatment group than that in the healthy group, the levels of IL-10 were significantly lower in the conventional SCIT group and the individualized SCIT group than that in the healthy group, but there was no difference between the conventional SCIT and the individualized SCIT group. CONCLUSION After 3 years treatment, there was no difference between conventional and individualized SCIT groups. But the efficacy of the conventional and individualized SCIT groups were significantly better than that in the drug symptomatic treatment group.
Desensitization, Immunologic ; Enzyme-Linked Immunosorbent Assay ; Humans ; Injections, Subcutaneous ; Interleukin-10 ; blood ; Precision Medicine ; Quality of Life ; Rhinitis, Allergic ; drug therapy ; Surveys and Questionnaires

Aortic Valve Insufficiency ; Heart Valve Prosthesis ; Heart Valve Prosthesis Implantation ; Humans ; Transcatheter Aortic Valve Replacement