膀胱癌微卫星不稳定及hMSH2基因突变研究

目的：研究膀胱癌微卫星不稳定及ｈＭＳＨ２基因突变情况。方法：应用Ｄ２Ｓ１１９及Ｄ２Ｓ１２３两个微卫星位点标记,ＰＣＲ法检测４５例膀胱癌标本微卫星不稳定;ＰＣＲ－ＳＳＣＰ银染法分析ｈＭＳＨ２基因外显子７、８、１５突变情况。结果：４５例膀胱癌中微卫星不稳定者有７例,微卫星不稳定发生率为１５．６％;在这７例微卫星不稳定标本中有３例同时检测出ＤＮＡ错配修复基因ｈＭＳＨ２突变,占微卫星不稳定总数的４２．９％,且均为体细胞突变。结论：微卫星不稳定和错配修复基因ｈＭＳＨ２突变可能参与膀胱癌癌变过程。     

错配修复hMLH3基因C2825T和A2173C突变在家族性食管癌中的意义

 目的 探讨错配修复基因hMLH3在家族性食管癌发病中的突变及其作用.方法 应用聚合酶链反应(PCR)、变性高效液相色谱分析(DHPLC)和直接测序法检测8个有遗传背景的食管癌家族的hMLH3基因突变情况.结果 在2个家系中发现了2处错义突变C2825T和A2173C.33%的突变发生于低风险的人群中,而高风险家系中有20%的基因突变.在2个家系中hMLH3的错义突变与食管癌发生有较强的相关性.结论 首次发现hMLH3基因C2825T和A2173C错义突变.hMLH3基因作为一新的风险基因,在家族性食管癌的发病中可能通过与其它基因互相叠加、共同起作用.     

Preattentive dysfunction in bipolar disorder: A MEG study using auditory mismatch negativity

Background

Neuropsychological studies have demonstrated that cognitive dysfunction represents pathophysiological mechanisms underlying bipolar disorder. However, information processing deficits in bipolar disorder have not often been examined electrophysiologically. Here, we examined preattentive processing and sensory information processing using mismatch field (MMNm) and P1m components, respectively, using magnetoencephalography.

Methods

Ten patients with bipolar disorder and 20 healthy volunteers participated in the study. The participants were presented with auditory stimuli sequences comprising standard and deviant stimuli. MMNm was elicited in response to changes in duration and frequency of pure-tone stimuli and a vowel across-category change.

Results

The magnetic global field power of MMNm in the right hemisphere under the pure-tone condition was significantly delayed in patients with bipolar disorder compared to healthy volunteers, and that of P1m did not differ between the two groups. The MMNm dipole in the left hemisphere was located inferior in patients with bipolar disorder than in healthy volunteers. This finding did not correlate with clinical symptoms.

Conclusions

Information processing at the preattentive level is impaired in patients with bipolar disorder irrespective of clinical symptoms, and this dysfunction is not due to sensory level dysfunction. The quality of preattentive information processing impairment is different between patients with bipolar disorder and patients with major depressive disorder, as shown by the MMNm latency and power differences.     

MEIA法与ELISA法检测26例血清HBsAg和HBeAg的比较

目的：比较微粒子酶免疫分析法（MEIA）与酶联免疫吸附试验（ELISA）法检测血清HBsAg和HBeAg的差异。方法：选择26例经ELISA法检测已确定乙肝五项中HBsAg阴性而HBeAg和HBcAb阳性（其中7例HBsAb阳性）的患者血清,应用MEIA法再次检测乙肝五项。结果：MEIA法检测结果显示,21例患者血清HBsAg呈现阳性（其中6例HBsAb阳性）,1例患者血清HBsAg仍呈现阴性（其HBsAb阳性）,4例患者血清HBsAg和HBeAg均呈现阴性。结论：MEIA法可减少假阴性、假阳性的发生,优于ELISA法。     

遗传性非息肉病性结直肠癌8个家系临床及病理分析

目的分析遗传性非息肉病性结直肠癌（HNPCC）家系临床及病理特点。方法收集符合Amsterdam标准Ⅱ的8例HNPCC家系资料,绘制家系图谱。结果HNPCC发病率为1.59%,8个HNPCC家系总发病人数为31例,其中结直肠癌患者为25例,肠外相关肿瘤6例,8例先证者中6例为女性,2例为男性,4例发病年龄小于40岁,发病部位位于右半结肠为2例,左半结肠3例,直肠3例,组织学分型以中至低分化腺癌为主;均未出现淋巴结及远处转移;8例先证者错配修复（MMR）蛋白表达异常的为5例。结论HNPCC先证者发病年龄轻,组织学分型较好,家系成员发病率高,对其家族成员进行定期检查和及时治疗将能有效地预防其发生并降低死亡率;MMR基因突变检测对提高HNPCC的诊断起重要作用。     

Therapy with pembrolizumab in treatment-naïve patients with nonmetastatic,mismatch repair deficient colorectal cancer

Therapy with immune checkpoint inhibitors (ICI) is effective in patients with metastatic mismatch-repair deficient (dMMR) colorectal cancer (CRC); however, data on treatment with neoadjuvant ICI in patients with locally advanced CRC are limited. From March 2019 to June 2020, five Danish oncological centers treated 10 patients with a treatment-naïve dMMR CRC with preoperative pembrolizumab, 9 with a nonmetastatic, unresectable colon cancer and 1 with a locally advanced rectum cancer. All 10 patients were evaluated regularly at a multidisciplinary team (MDT) meeting, and they all had a radical resection after a median of 8 cycles (range 2-13) of pembrolizumab. A microscopic evaluation of the resected tumors revealed no remaining tumor cells in five patients, while five still had tumor cells present. The patients were given no additional therapy. No recurrences were reported after a median follow-up of 26 months (range 23-38.5 months). Biopsies from Danish patients with CRC are routinely screened for dMMR proteins. In 2017, data from the Danish Colorectal Cancer Group showed that 19% (565/3000) of the patients with colon cancer and 1.5% (19/1279) of those with rectum cancer had an dMMR tumor. Among the patients with MMR determination, 26% (99/384) patients had a T4 dMMR colon cancer; thus, the 10 patients treated with neoadjuvant pembrolizumab comprised about 9% of the patients with a T4 dMMR colon cancer (9/99) and 5% of patients with dMMR rectal cancer (1/19). Therapy with pembrolizumab was feasible and effective. Larger prospective trials are needed to confirm our findings.     

Valence-dependent brain potentials of processing augmented feedback in learning a complex arm movement sequence

ERPs in the EEG were scrutinized in learning a complex arm movement sequence with the aim to examine valence effects on processing augmented feedback during practice. Twenty-four healthy subjects practiced one session with 192 feedback trials according to an adaptive bandwidth feedback approach with a high informational level of feedback information (i.e., amplitude and direction of errors). The bandwidth for successful performance (increase of a score for a monetary competition) was manipulated to yield a success rate (positive feedback frequency) of approximately 50% adaptive to the current performance level. This allowed a variation of feedback valence unconfounded by success rate. In line with our hypotheses, the EEG data showed a valence-dependent feedback-related negativity (FRN) and a later fronto-central component at the FCz electrode as well as a P300 component at the Pz electrode. Moreover, the P300 and amplitudes in the FRN time window reduced in the second half of practice but were still dependent on feedback valence. Behavioral adjustments were larger after feedback with negative valence and were predicted by the late fronto-central component. The data support the assumption of feedback valence-dependent modulation of attentional cognitive involvement in motor control and learning.     

Pediatric renal transplantation—A UNOS database analysis of donor–recipient size mismatch

Background

We used the BSAi (Donor BSA/Recipient BSA) to assess whether transplanting a small or large kidney into a pediatric recipient relative to his/her size influences renal transplant outcomes.

Methods

We included 14 322 single-kidney transplants in pediatric recipients (0–17 years old) (01/2000–02/2020) from the United Network for Organ Sharing database. We divided cases into four BSAi groups (BSAi ≤ 1, 1 < BSAi ≤ 2, 2 < BSAi ≤ 3, BSAi > 3).

Results

There were no differences concerning delayed graft function (DGF) or primary non-function (PNF) rates, whether the grafts were from living or brain-dead donors. In both transplants coming from living donors and brain-dead donors, cases with BSAi > 3 and cases with 2 < BSAi ≤ 3 had similar graft survival (p = .13 for transplants from living donors, p = .413 for transplants from brain-dead donors), and both groups had longer graft survival than cases with 1 < BSAi ≤ 2 and cases with BSAi ≤ 1 (p < .001). The difference in 10-year graft survival rates between cases with BSAi > 3 and cases with BSAi ≤ 1 reached around 25% in both donor types. The better graft survival in transplants with BSAi > 2 was confirmed in multivariable analysis.

Conclusions

There is no significant impact of donor-recipient size mismatch on DGF and PNF rates in pediatric renal transplants. However, graft survival is significantly improved when the donor's size is more than twice the pediatric recipient's size.