Breast cancer has been the second most common solid tumor that metastasizes to the central nervous system after lung cancer.Triple-negative breast cancer(TNBC)has an earlier occurrence and high incidence of brain metastasis with its associated poor prognosis and limited treatment options due to the presence of the blood-brain barrier and lack of targeted drugs.Local treatment,including surgery and radiation therapy,are still the main therapy for brain metastasis.Surgical resection can not only relieve neurologic impairment of brain metastasis patients,but also can clarify the pathological type.Moreover,surgical resection combined with radiotherapy can improve the prognosis of brain metastasis patients compared to surgery or radiotherapy alone.By now,whole-brain radiation therapy(WBRT)is still considered the gold standard for multiple brain metastases,and meningeal metastases,but it will lead to neurocognitive decline,so hippocampal avoidance is essential.For selected patients with oligometastases,stereotactic radiotherapy has replaced WBRT to reduce cognitive toxicity.However,local treatment of TNBC brain metastasis cannot control the progress of brain metastasis and has significant side effects,so systemic therapy is needed.Chemotherapy drugs such as capecitabine and cisplatin can penetrate the blood-brain barrier,but their efficacy is limited.Therefore,the research and development of new targeted drugs and the exploration of new targets are necessary for TNBC brain metastasis.Research has found that patients carrying germline BRCA1/2 mutations have a higher risk of brain metastasis.Currently,the poly adenosine diphosphate ribose polymerase(PARP)inhibitor demonstrated antitumor activity in patients with advanced breast cancer and a germline BRCA1/2 mutation,and it can penetrate the blood-brain barrier.The phase Ⅲ trial EMBRACA reported that the PARP inhibitor talazoparib can prolong the progression-free survival of TNBC patients with brain metastasis.In addition,antibody drug conjugates(ADCs)trastuzumab deruxtecan(T-DXd)can also penetrate the blood-brain barrier.Studies such as DEBBRAH have shown that T-DXd has significant therapeutic effects in HER2 positive brain metastasis patients,while research on HER2 low expression patients has not yet reached the endpoint,and its role in TNBC brain metastasis is worth looking forward to.Sacituzumab govitecan(SG)is also an ADC composed of an antibody targeting the human trophoblast cell-surface antigen 2.The phase Ⅲ ASCENT study showed that in the full population(including 61 patients with brain metastasis),SG could significantly prolong the progression-free survival of advanced TNBC patients compared to the patients who received chemotherapy.ANG1005,a novel taxane derivative,can cross the blood-brain barrier as well.A multicenter,open-label phase Ⅱ study revealed that ANG1005 could prolong overall survival of patients with brain metastasis.In addition,phosphoinositide3-kinase,(PI3K)/protein kinase(AKT)/mammalian target of rapamycin(mTOR)pathway inhibitors,fatty acid synthase inhibitors,and the drugs with new delivery systems have become potential treatment options for TNBC brain metastasis patients.Although the Impassion 130 reported that no benefit trend for immunotherapy in TNBC brain metastasis,basic research has shown that radiotherapy combined with immunotherapy has a synergistic effect.Currently,multiple clinical trials(NCT03483012,NCT03449238,etc.)are exploring the efficacy of radiotherapy combined with immunotherapy in brain metastasis,and the results are promising.This article reviewed the research progress of TNBC brain metastasis treatment.

Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia (SCAP). We prospectively enrolled consecutive SCAP patients admitted to ICU. Bronchoscopy was performed at bedside within 48 h of ICU admission, and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid. The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy. Sixty-seven patients were included. Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota (R² = 0.033; P = 0.018), followed by acute kidney injury (AKI; R² = 0.032; P = 0.011) and plasma MIP-1β level (R² = 0.027; P = 0.044). Random forest identified that the families Prevotellaceae, Moraxellaceae, and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results. Multivariable Cox regression showed that the increase in α-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements. The positive bacteria lab test results, AKI, and plasma MIP-1β level were associated with patients' lung microbiota composition on ICU admission. The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.
Acute Kidney Injury/complications* ; Bacteria/classification* ; Chemokine CCL4/blood* ; Community-Acquired Infections/microbiology* ; Humans ; Lung ; Microbiota/genetics* ; Pneumonia, Bacterial/diagnosis* ; Prognosis ; RNA, Ribosomal, 16S/genetics*

Objective ： To study the effect of temperature and light intensity on photosynthetic fluorescence parameters, volatile oil content, and growth of Atractylodes lancea and provide reference for the rational selection of cultivation environment for A. lancea. MethodWe determined the photosynthetic indexes (such as net photosynthetic rate, water use efficiency, and carboxylation rate), light response curve, CO₂ response curve, fluorescence parameters, and the content of four volatile oils in A. lancea under two temperature treatments (32 °C and 22 °C) and two light treatments (full light and shade). ResultThe net photosynthetic rate and water use efficiency of A. lancea under high temperature + strong light were significantly higher than those under high temperature + weak light and low temperature + strong light. The ability of A. lancea to use weak light at low temperature was the strongest, while the utilization rate of weak light under strong light significantly reduced. The photosynthetic rate of A. lancea at low temperature was more susceptible to light intensity and CO₂ concentration than that at high temperature. The maximum photosynthetic rate and apparent quantum efficiency under weak light were significantly higher than those under strong light. The photoreaction efficiency at high temperature was higher than that at low temperature. The total amount of volatile oil in A. lancea treated with high temperature + weak light was the highest, reaching 4.582%. Compared with high temperature + strong light, high temperature + weak light significantly increased the content of hinesol and β-eudesmol in A. lancea by 91.7% and 35.7%, respectively, and low temperature + strong light significantly increased the content of hinesol by 87.5%. The content of β-eudesmol in low temperature + weak light treatment was significantly lower than that in high temperature + weak light treatment. ConclusionTThe growth of A. lancea was affected by the interaction between temperature and light. The light and temperature conditions required for the accumulation of volatile oil were not consistent with those suitable for the growth and development of A. lancea. A. lancea responded to the changes of light and temperature conditions by regulating the synthesis and accumulation of volatile oil.

Objective:To explore the correlation among childhood trauma, obsessive-compulsive symptoms, and implicit and explicit memory in patients with obsessive-compulsive disorder(OCD).Methods:Fifty-two OCD patients were enrolled, and the childhood trauma was investigated by using the childhood trauma questionnaire short-form(CTQ-SF). The degree of obsessive-compulsive symptoms was assessed by using the Yale-Brown obsessive symptoms scale (Y-BOCS). In addition, the abilities of implicit memory and explicit memory were tested by vocabulary perception speed tasks and vocabulary recognition tasks.According to the scores of CTQ-SF, the patients were divided into abuse group( n=26) and neglect group( n=26). SPSS 22.0 software was used for t-test and Pearson correlation analysis. Results:Results of obsessive-compulsive symptoms, implicit memory, and explicit memory showed no differences between the abuse group and the neglect group( t=-1.959-1.839, P>0.05). The scores of obsessions symptoms(12.52±4.61) were positively correlated with the total scores of CTQ-SF (40.10±10.20)( r=0.331, P<0.05). On the subscale, the scores of obsessions were positively correlated with the scores of physical abuse(7.89±3.02), sexual abuse(6.47±2.28)( r=0.373, P<0.01, r=0.356, P<0.05). There was a negative correlation between the scores of physical abuse and the accuracy of explicit memory(68.75±13.33)( r=-0.281, P<0.05). The scores of physical neglect(8.98±2.67) was positively correlated with implicit memory response time(4 285.94±2 067.42)( r=0.314, P<0.05). Conclusion:Obsessions in patients with OCD are related to traumatic childhood experiences, especially physical abuse and sexual abuse.Physical trauma may influence the level of implicit and explicit memory in patients with OCD.

Objective:To investigate the effects of long-chain non coding RNA (lncRNA) XIST on the proliferation and migration of pancreatic cancer PANC1 cells, and clarify the targeting relationship between lncRNA XIST and miR-101/enhancer of zeste homologz(EZH2).Methods:Ninety cases of pancreatic cancer surgically resected and pathologically confirmed in the first hospital of Jiaxing city from July 2010 to September 2018 and its corresponding paracarcinoma normal tissue were collected. PANC1 cells were divided into sh-XIST group, SH control group, MiR control group and miR-101 group. The expression of LncRNA XIST and miR-101 in pancreatic cancer tissue and PANC1 cells in each group were detected by fluorescence quantitative PCR. The relationship between the expression of LncRNA XIST and miR-101 and the clinicopathological parameters of tumor was analyzed. The proliferation and migration ability of PANC1 cells in each group were analyzed by CCK8 method and transwell chamber test. The EZH2 expression level of PANC1 cells in each group were analyzed by western blot. PANC1 cells in each group was inoculated into BALB/C nude mice with a cell density of 3×10 6 cells/100 μl and the tumor volume was measured. The relationship between LncRNA XIST and its miR-101 and targeting gene EZH2 were analyzed by bioinformatics and double luciferase reporter genes. Results:Compared with the paracancerous tissues, the level of LncRNA XIST in pancreatic cancer tissue was significantly increased 2.89±0.42 vs (1.12±0.22, P<0.05), and the level of miR-101 was significantly decreased 0.32±0.12 vs (1.25±0.22, P<0.05), and the differences were statistically significant ( P<0.05). LncRNA XIST expression in pancreatic cancer tissue was obviously increased along with higher differentiation degree, advanced TNM stage and lymph node metastasis, while miR-101 was greatly decreased. Compared with the cells in the sh-control group, the expression level of LncRNA XIST in the sh-XIST group was significantly decreased (0.34±0.18 vs 1.21±0.27). Compared with miR-control cells, the level of miR-101 cells in miR-101 group significantly increased (2.94±0.31 vs 1.54±0.29 ), and the differences were statistically significant ( P<0.05). After 72 h cell culture, the light absorption value at 450 nm in sh-control group, sh-XIST group, miR-control group and miR-101 group was 1.98±0.24, 1.21±0.20, 1.87±0.21 and 1.11±0.17; the number of transmembrane cells were (74.25±6.79 ), (29.11±5.17), (61.27±5.19) and (20.47±4.58)per 200 times visual field; the cell proliferation activity and migration ability in sh-XIST group were significantly decreased than sh-control group, miR-101 group and miR-control group and the xenograft tumor grew obviously slowly, all the differences were statistically significant (all P<0.05). Conclusions:LncRNA XIST can target miR-101/EZH2, regulating the proliferation and migration of pancreatic cancer cells, which promotes the occurrence and development of pancreatic cancer.

Objective To identify pathological mutation of D4Z4 in a child with facioscapulohumeral muscular dystrophy (FSHD) presented initially as mental retardation.Methods Wechsler Intelligence Scale for Children Revised in China (WISC-Ⅳ) was used to assess the patient's IQ.Other clinical data was also collected.With genomic DNA extracted from peripheral blood samples,the child and his parents were subjected to medical exome sequencing and copy number variation analysis by next generation sequencing (NGS).The D4Z4 repeats and their origin source were determined by molecular combing.Results By the WISC-Ⅳ test,the child was found to have a total IQ of 41,with a speech comprehension IQ of 45,and perceptual inference index IQ of 52.No pathological mutation was detected by NGS.By molecular combing method,the child was found to carry a D4Z4 spanning 5.2 kb with a copy number of 2.Analysis of his parents indicate that the mutation was de novo.Conclusion The D4Z4 copy number variation may account for the FSHD and mental retardation in the child.The molecular combing method can be used to identify the number of repeat units and facilitate the diagnosis of FSHD.

Objective To explore the clinical characteristics and treatment of a family with inherited generalized epilepsy with febrile seizures plus (GEFS+) caused by STX1B gene mutation and to review the literature.Methods Clinical data of a child with GEFS+ and his family members who visited Guangzhou Women and Children Medical Center in August 2017 were collected.DNA samples of the proband and his parents,his grandparents were analyzed by the next-generation sequencing and confirmed by Sanger sequencing.A literature search with "STX1B " as the key word was conducted at PubMed,China National Knowledge Infrastructure and Wanfang databases to include recently published studies (up to May 2018).Results The proband was a 2-year-old boy who was admitted to our hospital because of frequent epileptic seizures in a month,with focal seizures evolving into the generalized bilateral tonic-clonic epileptic attacks after febrile seizure.His seizures were well controlled by levetiracetam.His father presented febrile seizure in early childhood stage and epilepsy in adult stage,which were under control with lamotrigine.The proband's grandmother had a history of febrile seizure.Other family members had no history of convulsion.Ictal electroencephalogram showed low voltage fast activities (8-10 Hz) originating from the central region of the brain.Heterozygous mutation of STX1B gene (c.705C＞G,p.Asn235Lys) was detected in the proband,his father and grandmother.The mutation has not been reported previously.Furthermore,no other family members carried the mutation at c.705 locus of STX1B gene.No article in Chinese was found,and 4 articles in a language other than Chinese provided the complete case data of 9 mutation loci in 33 patients (4 families and 4 sporadic cases).With this research data (3 cases in 1 family) included,there were 36 cases and 10 mutation sites in STX1B gene.Of these mutations,there were 5 missense mutations,3 nonsense mutations,1 insert mutation and 1 deletion mutation;and according to the mutation distribution,there were 4 mutation sites in exon 3,2 in exon 8,2 in exon 9,and 1 in exon 1.There was incomplete penetrance in the family,so different types of epileptic attacks occurred among different family members.Conclusions In this study,a de novo mutation of STX1B gene in a family with GEFS+ was defined,which would expand the gene mutation spectrum and provide basis for family genetic counseling.Clinical heterogeneity was found in this family.Seizures caused by STX 1B gene mutation were sensitive to antiepileptic drugs.

Objective: To investigate the hospital employee satisfaction and trustworthiness in the background of the trusteeship mode and to find out the problems after trusteeship.Methods: Minnesota satisfaction questionnaire (MSQ) and the self-made questionnaire were used to conduct the survey.Results: The overall employee satisfaction (3.80±0.86) and trustworthiness (3.95±0.77)were higher.The highest level of trustworthiness concerned the cultural connotation (84.8%) followed by the management concept (82.8%) for overall satisfaction.The lowest level of employee satisfaction concerned income and workload (53.7%), followed by the working conditions and environment (55.3%).The administrative staff satisfaction was higher compared to that of medical staff (p=0.001), which showed significant statistical differences.Conclusions: The hospital has made some achievements after the trusteeship system reform, however, it still needs improvement and further strengthening in many aspects.The hospital must always keep abreast of the demands of workforce and improve the staff satisfaction so as to promote its continuous and sustainable development.

Objectives To provide genetic counseling and prenatal molecular diagnosis for two families with megalencephalic leukoencephalopathy with subcortical cysts (MLC).Methods Two MLC patients (probands 1 and 2) were admitted to the Department of Pediatrics of Peking University First Hospital in June 2011 and June 2009,respectively.Peripheral blood was collected and DNA sequencing was performed for genetic analysis for the two MLC patients and their parents.Amniotic fluid and villus of two fetuses (fetus 1 and 2) were collected at 21+4 and 12+3 weeks of gestational age from their mothers when they were pregnant again.The genomic DNA of the two fetuses was extracted and corresponding sites of MLC1 gene were sequenced.Haplotype analysis using a combination of 3 microsatellite markers (AR,DXS6807 and DXS6797) on chromosome X and sex determining region of Y chromosome was performed to detect maternal cell contamination.Verification of the prenatal molecular diagnosis and follow up study after birth were conducted for both fetuses.Results Macrocephaly,motor development delay and typical findings on brain MRI were identified in the two probands,and were clinically diagnosed with MLC.Compound heterozygous mutations were detected in proband 1 [c.353C＞T (p.T118M) and c.803C＞G (p.T268R)] and proband 2 [c.353C＞T (p.T118M) and c.836T＞C(p.L279P)],respectively.MLC was genetically diagnosed.Heterozygous variation in c.353[c.353C＞T (p.T118M)] and wild c.803C were identified in fetus 1,and both wild c.353C and c.836T were found in fetus 2.No maternal cell contamination was detected in both fetuses.Sequencing the corresponding sites after birth confirmed the prenatal diagnosis,and the head circumference and motor development were normal in fetus 1 at 5 months old.No macrocephaly was found and no DNA sequencing was done in fetus 2 at one month old.Conclusions Genetic counseling and prenatal molecular diagnosis for MLC families combined with clinical and genetic diagnosis are important in preventing MLC.Haplotype analysis with a combination of three microsatellite markers on chromosome X and sex determining region of Y chromosome is useful in detecting maternal cell contamination and avoiding its influence on prenatal diagnosis,and confirming the reliability of prenatal diagnosis.