内分泌和化疗对乳腺肿瘤患者干细胞的影响

BACKGROUND:Tumor stem cells are the root of cancer recurrence and metastasis, so clinical researches should focus on the effects of different treatments on tumor stem cells. OBJECTIVE:To explore the effects of endocrine therapy and chemotherapy on stem cells in patients with breast cancer. METHODS:After recovery and cultivation of estrogen receptor-positive human breast cancer cell lines MCF-7, passage 3 cells in logarithmic phase were selected and divided into three groups containing control, estradiol and estradiol with tamoxifen groups. The estradiol group was divided into three subgroups: 10^-7, 10^-8 and 10^-9 mol/L estradiol was added into the medium, respectively; the estradiol with tamoxifen group was divided into three subgroups: 10^-7, 10^-8 and 10^-9 mol/L estradiol with 10^-6 mol/L tamoxifen were added into the medium, respectively. The same amount of absolute ethyl ethanol was added into the medium of control group. Fifteen female patients with late recurrence and metastasis of breast cancer received chemotherapy as recurrence and metastasis group. Another 15 healthy volunteers were selected as healthy control group. RESULTS AND CONCLUSION:The proportion of CD44⁺CD24^-/low cell subsets in the estradiol and estradiol with tamoxifen groups was significantly higher than that of the control group (P < 0.05), and the proportion of CD44⁺CD24^-/low cell subsets in the estradiol group was significantly higher than that of the estradiol with tamoxifen group at the same concentration (P < 0.05). The proportion of CD44+CD24-/low cell subsets had no significant differences among groups at 10 and 20 days of culture (P < 0.05). The proportion of CD44⁺CD24^-/low cell subsets significantly increased in MCF-7 cells after 24-hour intervention with different chemotherapy drugs. But only the proportion of CD44⁺CD24^-/low cell subsets in the paclitaxel and doxorubicin groups was significantly higher than that of the control group after 20-day intervention (P < 0.05). Besides, the proportion of CD44⁺CD24^-/low cell subsets in the peripheral blood of healthy volunteers was significantly lower than that of the recurrence and metastasis group (P < 0.05). Among 15 patients with late recurrence and metastatic of breast cancer, 9 had stable disease, 5 had partial remission, 1 had failed chemotherapy and cancer progression. Moreover, the proportion of CD45^-CD44⁺CD24^-/low cell subsets in the peripheral blood of patients sensitive for chemotherapy was significantly lower than that before treatment (P < 0.05). In conclusion, both endocrine therapy and chemotherapy exert a certain effect on the CD44⁺CD24^-/low cell subsets of breast cancer positive for estrogen receptor. Given that CD44⁺CD24^-/low cell subsets in MCF-7 cells resist chemotherapy drugs, the proportion of CD45^-CD44⁺CD24^-/low cells in the peripheral blood of patients sensitive for chemotherapy is decreased.     

Exploring the utility of whole‐exome sequencing as a diagnostic tool in a child with atypical episodic muscle weakness

The advent of whole‐exome next‐generation sequencing (WES) has been pivotal for the molecular characterization of Mendelian disease; however, the clinical applicability of WES has remained relatively unexplored. We describe our exploration of WES as a diagnostic tool in a 3½‐year old female patient with a 2‐year history of episodic muscle weakness and paroxysmal dystonia who presented following a previous extensive but unrevealing diagnostic work‐up. WES was performed on the proband and her two parents. Parental exome data was used to filter potential de novo genomic events in the proband and suspected variants were confirmed using di‐deoxy sequencing. WES revealed a de novo non‐synonymous mutation in exon 21 of the calcium channel gene CACNA1S that has been previously reported in a single patient as a rare cause of atypical hypokalemic periodic paralysis. This was unexpected, as the proband's original differential diagnosis had included hypokalemic periodic paralysis, but clinical and laboratory features were equivocal, and standard clinical molecular testing for hypokalemic periodic paralysis and related disorders was negative. This report highlights the potential diagnostic utility of WES in clinical practice, with implications for the approach to similar diagnostic dilemmas in the future.     

Evaluation of Anti-Bacterial and Wound Healing Activity of the Fruits of Amorpha Fruticosa L.

As the traditional Chinese medicine, the fresh fruits of Amorpha fruticosa L. were applied for the treatment of carbuncle, eczema and burn (Das et al., 2007). However, little is known about the functional roles of the fruits of Amorpha fruticosa L. during wound healing progress. In the present study, we evaluated both antimicrobial potential against a wide range of microorganisms and wound healing activity of the seven compounds isolated from the fruits of Amorpha fruticosa L in vitro and in vivo. Our results showed that compounds I (6a,12a-dehydroamorphin), V (dehydrosermundone) and VI (tephrosin) isolated from the fruits of Amorpha fruticosa L. performed dominant antimicrobial potential against microorganisms. Moreover, these compounds significantly enhanced fibroblasts proliferation and migration, leading to promotion of wound healing. Thus, it could be possible for the therapeutic utilization of Amorpha fruticosa L. for wound healing in the future.     

Mycobacterium tuberculosis Region of Difference (RD) 2 Antigen Rv1985c and RD11 Antigen Rv3425 Have the Promising Potential To Distinguish Patients with Active Tuberculosis from M. bovis BCG-Vaccinated Individuals

Antigens encoded in the region of difference (RD) of Mycobacterium tuberculosis constitute a potential source of specific immunodiagnostic antigens for distinguishing tuberculosis (TB) infection from BCG vaccination. We evaluated the diagnostic potential of specific T-cell epitopes selected from two immunodominant antigens, Rv1985c and Rv3425, from RD2 and RD11, respectively, on the basis of epitope mapping, in TB patients and BCG-vaccinated healthy individuals. Using a whole-blood gamma interferon release assay, a wide array of epitopes was recognized on both Rv1985c and Rv3425 in TB patients. Those epitopes that could specifically discriminate TB infection from BCG vaccination were carefully selected, and the most promising peptide pools from Rv1985c showed a sensitivity of 53.9% and a specificity of 95.5%. When the novel specific peptides from Rv1985c joined the diagnostic antigens in the QuantiFERON-TB Gold In-Tube (QFT-IT) assay, the sensitivity was increased from 86.4% to 96.2%, with no drop in specificity. These results indicate that the peptide pools selected from Rv1985c and Rv3425 have the potential to diagnose TB infection by a method that may be routinely used in clinical laboratories.     

Interleukin-33 alleviates psoriatic inflammation by suppressing the T helper type 17 immune response

Psoriasis is a chronic inflammatory skin disease with unclear pathogenesis. Interleukin-33 (IL-33) is highly expressed in patients with psoriasis, but its role in psoriasis is unknown. The aim of this study was to investigate the possible role of IL-33 in the pathogenesis and treatment of psoriasis. IL-33 expression was determined using enzyme-linked immunosorbent assay, real-time fluorescent quantitative polymerase chain reaction and immunohistochemical staining. CD4⁺ T cells were sorted using magnetic beads and treated with or without IL-33. Imiquimod (IMQ) was used to induce psoriatic inflammation in mice. The frequency of immune cells was determined using flow cytometry. The cytokine level in mouse skin was measured using cytometric bead array. Our results showed that IL-33 was highly expressed in the lesional skin and serum of patients with moderate-to-severe plaque psoriasis. IL-33 inhibited the expression of IL-17 in CD4⁺ T cells of psoriasis patients. Subcutaneous injection of IL-33 alleviated the IMQ-induced psoriatic inflammation in mice, reduced tumor necrosis factor-α and IL-23 expression, and decreased the proportion of T helper type 17 (Th17) cells in the skin-draining lymph nodes in the mice. Our results suggest that IL-33 plays a protective role in the pathogenesis of psoriasis by suppressing Th17 cell differentiation and function. The potential therapeutic effect of IL-33 in treating psoriasis warrants further investigation.     

内镜下离断直肠尿道瘘黏膜预防先天性肛门闭锁术后尿道并发症

目的探讨小婴儿在先天性肛门闭锁二期手术中,在直肠腔内应用胃镜离断直肠尿道瘘交界部黏膜及黏膜下层的作用。方法收集2020年1月至2020年5月在首都儿科研究所附属儿童医院普通外科因先天性肛门闭锁伴直肠尿道瘘行二期肛门成形术8例患儿的病例资料。所有患儿均为先天性肛门闭锁伴直肠尿道瘘已行一期结肠造瘘术后。均为男性患儿,平均手术年龄为3.9个月,手术年龄范围为2.8~6.3个月;平均体重为7.5 kg,体重范围为5.9~9.0 kg;造瘘口位于右上腹1例,脐上中腹部3例,左上腹2例,左下腹2例。因为本研究患儿年龄较小,肠腔细小、薄弱,故应用成人的普通电子胃镜在结肠、直肠内操作。在二期肛门成形术中,均在胃镜下尝试离断直肠尿道瘘交界部黏膜及黏膜下层组织,在胃镜离断黏膜后,再行腹腔镜辅助肛门成形术。结果8例患儿,1例经胃镜多次尝试仍未能到达直肠末端而放弃胃镜下黏膜离断术。1例因术中呼吸循环不稳定,仅在胃镜下完成交接部黏膜离断术,而未连续完成腹腔镜下肛门成形术,5 d后在腹腔镜下完成肛门成形术。其余6例均完成胃镜下瘘口交界部黏膜及黏膜下离断术,并同期行腹腔镜下肛门成形术。二期术后两周行尿道造影复查未见尿道狭窄和尿道憩室。结论运用胃镜在直肠腔内游离直肠尿道瘘交界部黏膜及黏膜下组织的操作方法是可行、有效的,是目前比较准确和全新的辅助直肠末端离断的方法,也是胃镜和腹腔镜联合手术完成肛门成形术的有益尝试。     

Cumulative live birth rates of in vitro fertilization/intracytoplasmic sperm injection after multiple complete cycles in China

There were few studies of cumulative live birth rates (CLBRs) based on multicenter reproductive clinical data from the general Chinese population. Here we report a retrospective cohort study, including 14 311 women with 17 315 cycles, in three reproductive centers to evaluate two estimated parameters of CLBRs with multiple transfer cycles of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in a Chinese population. We found that CLBRs were related to female age and endometrial thickness. By the fourth transfer cycle, the conservative and optimal estimates of CLBRs were 52.95% and 77.30% in women under 30 years of age, and 18.17% and 26.51% in those 37 years of age or older, respectively. The two estimates were 44.70% and 63.15% in women with endometrial thickness more than 7 mm, and 32.05% and 46.18% in those with less than 7 mm, respectively. In addition, body mass index (BMI), duration of infertility, and infertility diagnoses may also be related to CLBRs on certain conditions. The findings from this study on CLBRs after multiple transfer cycles of IVF/ICSI treatment on different conditions in the Chinese population should be beneficial to both infertile couples and clinicians.     

耳后注射甲强龙作为补救方案在中高频听力下降型突发性聋治疗中的疗效及可行性分析

目的探析中高频听力下降型突发性聋采取耳后注射甲强龙治疗的临床效果及可行性。方法选取2019年5月~2020年7月本院耳鼻喉科就诊的中高频听力下降型突发性聋患者,共纳入病例54例,以随机法分组,即常规组(n=27)和观察组(n=27),常规组予常规治疗,观察组采取耳后注射甲强龙,比较两组效果。结果观察组有效率相比于常规组显著提高(P<0.05);治疗3周后,观察组2000~8000Hz频率听力提高值与常规组比(P<0.05)。结论中高频听力下降型突发性聋采取耳后注射甲强龙治疗效果理想,值得推广。     

胰岛细胞分化与胚体发育的相关性研究

目的探讨胚胎发育中胎龄及胚体大小与胰岛细胞分化的相关性。方法收集妊娠6～14周的胚胎20例,测其重量,顶臀径并通过免疫组织化学染色观察胰高血糖素（glucagon）在胰岛细胞分化过程中的表达。结果妊娠9周左右,胚体重约2．89±0．12g,顶臀径约80．0±2．8mm,此时胰腺导管上皮细胞开始分化出胰岛细胞,并且具有内分泌功能。结论妊娠发育的胚胎在胎龄9w、顶臀径30mm、重量约为2．89g左右时,胰岛细胞开始从胰腺导管上皮细胞分化。     

医源性血管损伤的预防和术中处理

目的：总结手术中发生医源性血管损伤的处理经验。方法：10例在外科手术中损伤血管的患者,其中门静脉,下腔静脉、髂总静脉损伤各2例,股总静脉、颈总动脉、腋静脉、腘动脉损伤各1例。行血管修补术5例,行端-端吻合术1例,自体静脉移植术1例,人工血管移植1例,钳夹止血1例,血管结扎1例。结果：本组痊愈8例;死亡2例,其中下腔静脉损伤止血失败死亡1例,颈总动脉损伤结扎死亡1例。结论：医源性血管损伤重在预防,一旦发生血管损伤,迅速有效地控制出血是手术成功的关键,血管修补或吻合术疗效良好。