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We introduce the southern stellar stream spectroscopy survey (S 5), an on-going program to map the kinematics and chemistry of stellar streams in the southern hemisphere. The initial focus of S 5 has been spectroscopic observations of recently identified streams within the footprint of the dark energy survey (DES), with the eventual goal of surveying streams across the entire southern sky. Stellar streams are composed of material that has been tidally striped from dwarf galaxies and globular clusters and hence are excellent dynamical probes of the gravitational potential of the Milky Way, as well as providing a detailed snapshot of its accretion history. Observing with the 3.9 m Anglo-Australian Telescope's 2-degree-Field fibre positioner and AAOmega spectrograph, and combining the precise photometry of DES DR1 with the superb proper motions from Gaia DR2, allows us to conduct an efficient spectroscopic survey to map these stellar streams. So far S 5 has mapped nine DES streams and three streams outside of DES; the former are the first spectroscopic observations of these recently discovered streams. In addition to the stream survey, we use spare fibres to undertake a Milky Way halo survey and a low-redshift galaxy survey. This paper presents an overview of the S 5 program, describing the scientific motivation for the survey, target selection, observation strategy, data reduction, and survey validation. Finally, we describe early science results on stellar streams and Milky Way halo stars drawn from the survey. Updates on S 5, including future public data releases, can be found at http://s5collab.github.io. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the role of Fcgamma receptors (FcgRs) to lupus nephritis in Chinese people. The study uses the relative standard curve method to calculate the copy number of the Fcgr3B genes which plays a unique role in coupling the humoral and cellular immune response. The study founds that neutrophil antigen 2 (NA2) genotype increases copy number group in healthy control of lupus nephritis.

Objective: To investigate the effect of anatomical unit resection on the overall survival rate of patients with T4 stage posterior buccal carcinoma. Methods: We conducted a retrospective study on 79 patients with T4 stage posterior buccal squamous cell carcinoma underwent radical surgery for buccal mucosa cancer and reconstruction with free anterolateral thigh flap in the Department of Oral and Maxillofacial Surgery, the Second Xiangya Hospital, Central South University from March 2014 to December 2019. The 74 patients were males and the 5 patients were females, aged from 28 to 72 years old. The 40 patients in control group underwent traditional extended resection (1.5-2.0 cm safe margin), and 39 patients in the experimental group underwent anatomical unit resection. The clinicopathological parameters of patients were collected and followed up regularly. The overall survival rate was assessed by Log-rank and Cox proportional risk regression model. Multivariate analysis was performed by linear regression model. Results: There were significant differences between experimental group and control group in overall survival rates (61.53% vs 27.50%, χ 2 =6.624, P =0.010) and local disease control rates (74.36% vs 27.50%, χ 2 =17.350, P <0.001). Multiple linear regression analysis showed that local disease control rate was significantly correlated with anatomical unit resection ( t =3.880, P <0.001) and lymph node metastasis ( t =2.619, P =0.011), and also Cox proportional hazards regression model analysis identified that overall survival rate was significantly correlated with anatomical unit resection ( Z =2.421, P =0.016) and lymph node metastasis ( Z =2.793, P =0.005). Conclusion: For posterior buccal carcinoma with multiple anatomical units involved, anatomical unit resection can significantly reduce local recurrence and improve overall survival rate of patients.

Objective: To analyze the disease characteristics, diagnosis and treatment methods of venous pulsatile tinnitus treated by intervention of sigmoid sinus. Methods: Fifty patients (from Shandong Provincial ENT Hospital, Shandong University between February 2014 and July 2020) with venous pulsatile tinnitus treated by sigmoid sinus surgery were analyzed retrospectively. The tinnitus characteristics, imaging findings, surgical methods, intraoperative findings and postoperative tinnitus changes were recorded. The patients were followed up for 6-12 months. The sign rank sum test was used to analyze the difference in tinnitus grading before and after surgery. There were 50 patients with unilateral venous pulsatile tinnitus, including 49 females and 1 male. The age ranged from 17 to 67 years, with a median age of 44 years. There were 45 cases of right tinnitus and 5 cases of left tinnitus. The degree of tinnitus before operation was grade Ⅱ or above, including 4 cases of gradeⅡ, 11 cases of grade Ⅲ, 22 cases of grade Ⅳ and 13 cases of grade Ⅴ. Results: Thirty-seven cases were cured, 8 cases were ineffective (no change in tinnitus), 3 cases were markedly effective (tinnitus grade decreased by 3 in 2 cases, 4 in 1 case), and 2 cases were effective (tinnitus grade decreased by 1). The difference of tinnitus grade before and after operation was statistically significant ( Z =-5.70, P <0.05). Temporal bone CT showed 36 cases of sigmoid diverticulum (including 17 cases with sigmoid sinus dehiscence), 12 cases of sigmoid sinus dehiscence and 2 cases of absence of the temporal bone cortex abutting to sigmoid sinus. Thirty-five cases were performed with closure of sigmoid sinus diverticulum, 4 cases were performed with resurfacing of the sigmoid plate, 5 cases were performed with narrowing of sigmoid sinus, 4 cases were performed with simple opening of pre sigmoid mastoid air chamber, 1 case of opening was performed with pre sigmoid mastoid air chamber combined with narrowing of sigmoid sinus, and 1 case was performed with opening of pre sigmoid mastoid air chamber combined with closure of sigmoid sinus diverticulum. Conclusions: Venous pulsatile tinnitus is common in women. The common causes may be sigmoid sinus wall abnormalities such as sigmoid sinus diverticulum and perisigmoid bone defect. Imaging examinations are helpful for diagnosis. Venous pulsatile tinnitus can be treated with surgery.

Objective: To demonstrate the type of CEBPA gene mutations among patients with acute myeloid leukemia (AML), clinical characteristics, and prognostic effect on patient outcomes. Methods: Demographic data, clinical features, laboratory characteristics, and data about treatment and follow-up of 57 patients with CEBPA mutated AML diagnosed at Peking Union Medical College Hospital between April 2016 and November 2022 were collected and analyzed. Results: In total, 57 patients with CEBPA mutation accounted for 16.1% of all the 353 patients with AML, among which 28 patients had CEBPA-bZIPinf and 29 had CEBPA-other. Compared with the CEBPA-other group, the CEBPA-bZIPinf group was younger (54 vs 64 years, P =0.010), de novo AML was more common ( P =0.001), and the level of bone marrow blast was higher (68.0% vs 36.3%, P =0.001). Moreover, 24 patients from the CEBPA-bZIPinf group and 19 from the CEBPA-other group received chemotherapy. The one-course complete remission (CR) rate of the CEBPA-bZIPinf group was significantly higher than that of the CEBPA-other (87.5% vs 47.4%, P =0.010) and CEBPA-wt (87.5% vs 50.3%, P =0.002) groups. After a median follow-up of 11 months, the median OS of the CEBPA-bZIPinf group was significantly longer than that of the CEBPA-wt group (not reached vs 22.1 months, P =0.012) . Conclusion: CEBPA-bZIPinf mutated AML is a unique clinical entity, with a younger age of diagnosis, better response to chemotherapy, and better prognosis.

Objective: To investigate the clinical features and genetic features of combined oxidative phosphorylation deficiency 32 (COXPD32) caused by MRPS34 gene variation. Methods: The clinical data and genetic test of a child with COXPD32 hospitalized in the Department of Neurology, Children's Hospital, Capital Institute of Pediatrics in March 2021 were extracted and analyzed. A literature search was implemented using Wanfang, China biology medicine disc, China national knowledge infrastructure, ClinVar, human gene mutation database (HGMD) and Pubmed databases with the key words "MRPS34" "MRPS34 gene" and "combined oxidative phosphorylation deficiency 32" (up to February 2023). Clinical and genetic features of COXPD32 were summarized. Results: A boy aged 1 year and 9 months was admitted due to developmental delay. He showed mental and motor retardation, and was below the 3 rd percentile for height, weight, and head circumference of children of the same age and gender. He had poor eye contact, esotropia, flat nasal bridge, limbs hypotonia, holding instability and tremors. In addition, Grade Ⅲ/6 systolic murmur were heard at left sternal border. Arterial blood gases suggested that severe metabolic acidosis with lactic acidosis. Brain magnetic resonance imaging (MRI) showed multiple symmetrical abnormal signals in the bilateral thalamus, midbrain, pons and medulla oblongata. Echocardiography showed atrial septal defect. Genetic testing identified the patient as a compound heterozygous variation of MRPS34 gene, c.580C>T (p.Gln194Ter) and c.94C>T (p.Gln32Ter), with c.580C>T being the first report and a diagnosis of COXPD32. His parents carried a heterozygous variant, respectively. The child improved after treatment with energy support, acidosis correction, and "cocktail" therapy (vitaminB 1 , vitaminB 2 , vitaminB 6 , vitaminC and coenzyme Q10). A total of 8 cases with COXPD32 were collected through 2 English literature reviews and this study. Among the 8 patients, 7 cases had onset during infancy and 1 was unknown, all had developmental delay or regression, 7 cases had feeding difficulty or dysphagia, followed by dystonia, lactic acidosis, ocular symptoms, microcephaly, constipation and dysmorphic facies(mild coarsening of facial features, small forehead, anterior hairline extending onto forehead,high and narrow palate, thick gums, short columella, and synophrys), 2 cases died of respiratory and circulatory failure, and 6 were still alive at the time of reporting, with an age range of 2 to 34 years. Blood and (or) cerebrospinal fluid lactate were elevated in all 8 patients. MRI in 7 cases manifested symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia. Urine organic acid test were all normal but 1 patient had alanine elevation. Five patients underwent respiratory chain enzyme activity testing, and all had varying degrees of enzyme activity reduction. Six variants were identified, 6 patients were homozygous variants, with c.322-10G>A was present in 4 patients from 2 families and 2 compound heterozygous variants. Conclusions: The clinical phenotype of COXPD32 is highly heterogenous and the severity of the disease varies from development delay, feeding difficulty, dystonia, high lactic acid, ocular symptoms and reduced mitochondrial respiratory chain enzyme activity in mild cases, which may survive into adulthood, to rapid death due to respiratory and circulatory failure in severe cases. COXPD32 needs to be considered in cases of unexplained acidosis, hyperlactatemia, feeding difficulties, development delay or regression, ocular symptoms, respiratory and circulatory failure, and symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia, and genetic testing can clarify the diagnosis.

Objective: To analyze the clinical characteristics and treatment of middle ear myoclonus. Methods: Fifty-six cases of middle ear myoclonus were enrolled in Shandong Provincial ENT Hospital, Shandong University from September 2019 to August 2021, including 23 males and 33 females. The age ranged from 6 to 75 years, with a median age of 35 years; Forty-seven cases were unilateral tinnitus, nine cases were bilateral tinnitus. The time of tinnitus ranged from 20 days to 8 years. The voice characteristics, inducing factors, nature (frequency) of tinnitus, tympanic membrane conditions during tinnitus, audiological related tests, including long-term acoustic tympanogram, stapedius acoustic reflex, pure tone auditory threshold, short increment sensitivity test, alternate binaural loudness balance test, loudness discomfort threshold, vestibular function examination, facial electromyography, and imaging examination were recorded. Oral carbamazepine and/or surgical treatment were used. The patients were followed up for 6-24 months and the tinnitus changes were observed. Results: Tinnitus was diverse, including stepping on snow liking sound, rhythmic drumming, white noise, and so on. The inducing factors included external sound, body position change, touching the skin around the face and ears, speaking, chewing and blinking, etc. Forty-four cases were induced by single factor and 9 cases were induced by two or more factors. There was no definite inducing factor in 1 case. One patient had tinnitus with epilepsy. One case of traumatic facial paralysis after facial nerve decompression could induce tinnitus on the affected side when the auricle moved. Tympanic membrane flutter with the same frequency as tinnitus was found in 12 cases by otoscopy, and the waveform with the same frequency as tinnitus was found by long-term tympanogram examination. There were 7 patients with no tympanic membrane activity by otoscopy, the 7 cases also with the same frequency of tinnitus by long-term tympanogram examination, but the change rate of the waveform was faster than that of the patients with tympanic membrane flutter. All patients with tinnitus had no change in hearing. One case of tinnitus complicated with epilepsy (a 6-year-old child) was treated with antiepileptic drug (topiramate) and tinnitus subsided. One case suffered from tinnitus after facial nerve decompression for traumatic facial paralysis was not given special treatment. Fifty-four cases were treated with oral drug (carbamazepine), of which 10 cases were completely controlled and 23 cases were relieved; 21 cases were invalid. Among the 21 patients with no effect of carbamazepine treatment, 8 patients were treated by surgery, 7 patients had no tinnitus after surgery, 1 patient received three times of operation, and the third operation was followed up for 6 months, no tinnitus occurred again. The other 13 cases refused the surgical treatment due to personal reasons. Conclusions: Middle ear myoclonus tinnitus and the inducing factors manifestate diversity. Oral carbamazepine and other sedative drugs are effective for some patients, and surgical treatment is feasible for those who are ineffective for medication.

Objective: To investigate the efficacy of anterolateral thigh flap preforming tongue in patients with total glossectomy. Methods: A total of 27 patients with tongue cancer who underwent total glossectomy, neck lymph node dissection and anterolateral thigh flap transfer were collected from January 2019 to April 2021 in the Department of Oral and Maxillofacial Surgery at the Second Xiangya Hospital. All patients were males, the age ranged from 35-73 years. The patients were divided into experimental (14 cases) and control (13 cases) groups, based on whether the tongue was reconstructed. The clinical parameters of two groups were analyzed by independent sample t test or Fisher exact probability method. Results: The success rate of free flap was 100%, of the patients, 2 patients had cervical hematoma and 1 patient had wound infection postoperatively. There was no difference in speech (6.69±3.42 vs . 5.50±3.01, t =0.96, P =0.346) or swallowing (χ 2 =0.46, P =0.793) function between two groups at 1 month after surgery. However, the speech (24.94±7.43 vs . 18.44±6.30, t =2.48, P =0.020) and swallowing (χ 2 =6.97, P =0.008) functions in experimental group were significantly better than those in control group. No case was lost to follow-up. All patients were extubated after operation, with average time of 7.2 days in the experimental group and 7.7 days in the control group. The overall survival rate was 71.4% in the experimental group and 61.5% in the control group. Conclusion: The use of anterolateral thigh flap preforming tongue can improve the speech and swallowing functions in patients with total glossectomy and offer a novel method for tongue construction.

Objective: To investigate the effect of continuous intravenous infusion of subanesthetic dose of esketamine intraoperatively on postoperative opioid consumption in patients undergoing thoracoscopic surgery. Methods: A total of 71 patients with elective thoracoscopic lung surgery in the First Affiliated Hospital of Zhengzhou University from December 2020 to December 2021 were selected. Patients who were classified as grade Ⅰ or Ⅱ by the American Society of Anesthesiologists (ASA) and aged 18-70 years were included, including 32 males and 39 females, with a body mass index (BMI) of 18.5-30.0 kg/m 2 . The patients were randomly divided into three groups: (1) Control group (group C, n =24): continuous intravenous infusion of normal saline at the same rate during surgery; (2) Subanesthetic dose of esketamine 0.125 mg·kg -1 ·h -1 group (group ES1, n =23): continuous intravenous infusion of esketamine at a rate of 0.125 mg·kg -1 ·h -1 during surgery; (3) Subanesthetic dose of esketamine 0.250 mg·kg -1 ·h -1 group (group ES2, n =24): continuous intravenous infusion of esketamine at a rate of 0.250 mg·kg -1 ·h -1 during surgery. The main outcome measures were the total consumptions of hydromorphone of 3 groups within 24 and 48 hours after surgery. The secondary outcome measures were the extubation time, length of postanesthesia care unit (PACU) stay, the time of first feeding, and the incidences of adverse effects within 24 h after surgery in 3 groups. Results: The 24 h postoperative consumption of hydromorphone in group C, ES1 and ES2 was (5.4±1.0) mg, (4.5±1.5) mg and (4.0±0.8) mg, respectively. Likewise, the 48 h postoperative consumption of hydromorphone was (9.7±2.2) mg, (9.0±3.0) mg and (7.7±1.8) mg, respectively. Compared with group C, the 24 h postoperative hydromorphone consumptions were significantly reduced in group ES1 and ES2 (both P <0.05). The extubation time, length of PACU stay and the time of first feeding after surgery in group C were (23±10) min,(70±12) min,(17±3) h,in group ES1 were (22±4) min,(69±11) min,(14±5) h,in group ES2 were (16±8) min,(58±12) min,(14±3) h, respectively. Compared with group C and group ES1, both of the extubation time and length of PACU stay were shortened in group ES2 (both P <0.05). Compared with group C, the first postoperative feeding time of group ES1 and ES2 was shortened (both P <0.05). There were no differences in the incidences of adverse effects at postoperative 24 h among 3 groups (all P >0.05). Conclusion: Continuously intravenous infusion of subanesthetic esketamine at a rate of 0.250 mg·kg -1 ·h -1 can significantly reduce the postoperative opioid consumption and improve the patient's outcomes.

A pedigree genetic analysis of a female Duchenne muscular dystrophy (DMD) inherited from paternal chimerism was conducted to explore the genetic diagnosis strategy . No large deletions/duplications was found in the DMD gene of the proband. Next-generation sequencing (NGS) results showed that the proband had a heterozygous mutation in the DMD gene c.4707C>A (p.C1569X). This locus has not been reported in the literature and is considered as a pathogenic mutation. Sanger sequencing revealed that the father of the proband carried the same mutation, and the mosaic ratio was about 17.7%. The specific enzyme digestion test showed that the proband had maternal skewed X-inactivation. DMD a recessive inherited disease of the X chromosome, exists in female patients, and very few of them are inherited from paternal origin. Female patients need to pay close attention to skewed X-inactivation and suspected new mutations. Mosaic is not excluded, especially the inheritance of paternal mosaicism with normal phenotype. Prenatal gene screening is necessary for reproduction.

Objective: To explore the association between statins and colorectal cancer and provide evidence for the prevention of colorectal cancer. Methods: Literatures about statins and colorectal cancer published from January 2000 to January 2020 were retrieved from CNKI, Wanfang data, PubMed and Cochrane Library database. The literatures which met the inclusion criteria were collected, and the Newcastle-Ottawa Scale and Jadad score were used to assess the studies. Meta-analysis was performed with statistical software Revman 5.0 and Stata 12.1. Results: A total of 31 studies, involving more than 1.62 million subjects, were included in the analysis. The case-control study ( RR =0.93, 95% CI : 0.88-0.98), the cohort study ( RR =0.75, 95% CI : 0.63-0.88) and the randomized controlled trial ( RR =0.79, 95% CI : 0.65-0.97) showed moderate protective effect of statins. Using statin <5 years ( RR =0.86, 95% CI : 0.76-0.96), average daily dosage ≥34 mg ( RR =0.81, 95% CI : 0.66-0.98) and lipid-soluble statins ( RR =0.86, 95% CI : 0.74-0.99) also had preventive effect on colorectal cancer; while lovastatin ( RR =1.07, 95% CI : 1.00-1.14) increased the risk of colorectal cancer. Conclusion: Statins have protective effect on colorectal cancer.

Objective: To investigate the clinical and genetic characteristics of developmental and epileptic encephalopathy (DEE) caused by syntaxin-binding protein 1 (STXBP1) gene mutation. Methods: The clinical data, gene variation and treatment outcome of 15 children with STXBP1 encephalopathy admitted to Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2014 to June 2019 were analyzed retrospectively. Results: Among 15 patients, 11 were male and 4 were female, age ranged from 2 months to 69 months. The clinical manifestations of 14 children were epilepsy and developmental delay (DD) and the remaining one showed developmental delay without seizure. The onset age of epilepsy ranged from two days to 19 months and 11 of them experienced the first attack before 1 year of age. The common seizure types were epileptic spasms and tonic seizures. Seven patients were diagnosed with Ohtahara syndrome or West syndrome. Epileptic form discharges were observed in the interictal electroencephalograms (EEG) of 11 patients, including multifocal discharges, suppression-burst and hypsarrhythmia. The brain magnetic resonance imaging of 7 children were abnormal, including myelin dysplasia, less white matter, lack of corpus callosum or hypoplasia. The follow-up time ranged from 2 months to 57 months, after the last follow-up, 3 cases were seizure free, 6 children showed partial response and the other 5 patients had no response on multitherapy. Six of 8 patients showed good responses to levetiracetam (LEV) monotherapy or in combination with other antiepileptic drugs (AEDs). Vigabatrin (VGB) was applied to 5 patients with epileptic spasms and 4 of them showed response. All patients showed different degrees of developmental delay while four of them showed autistic features. STXBP1 gene mutations were identified in all cases and there were 15 types of gene variations, including 8 missense mutations, 1 nonsense mutation, 5 frame shift mutations and 1 complex mutation. Five novel mutations were unreported before, including c.1193A>G, c.172delG, c.1769C>T, c.1038&#95;1039delCC, c.348&#95;351dupTGAA. Conclusions: Development delay and epilepsy are the major and independent clinical phenotypes in children with STXBP1 encephalopathy. The variation of STXBP1 gene is mainly de novo. Levetiracetam and vigabatrin may be more effective in epilepsy control than other AEDs.

Objective: To undersand the monitor of occupational hazards in the enterprises in the past 5 years, as well as the distribution of occupational disease hazards and their dynamic changes in their respective jurisdictions, for providing scientific basis for prevention and control of occupational diseases in relevant departments. Methods: Taking the method of cluster sampling, select the monitoring results of the occupational disease hazard factors commissioned by the Municipal Center for Disease Control and Prevention from 2014 to 2018 and the annual monitoring data of the network of the occupational hazard declaration system of the Safety Supervision Bureau, using chi-square test, trend Statistical analysis was performed by chi-square test or Fisher exact probability method. Results: There were 461 testing companies in the past 5 years, with a total of 15, 186 monitoring points and 43428 samples. The pass rate was 94.32% (14324/15186) . The pass rate was increasing year by year from 2014 to 2017 ( P <0.05) ; The pass rate of various occupational disease hazards surveillance were greater than 90% except the rate of physical factors. In 2014, the qualified rate of physical factors was the lowest, which was 86.99% (1558/1791) ; the production rate of different production scale enterprises in 2018 was higher than that of 2014. From 2014 to 2018, the number of inspection enterprises and the number of inspection points of the joint-stock economy and state-owned economic enterprises are both high, 58 (10091 points) and 71 (1830 points) respectively; The qualified rate of state-owned economy and collective economy monitoring is high, 98.36% (1800/1830) and 100% (74/74) respectively. It had reached more than 95%; The enterprises tested mainly from the economic development zone and Guangling, respectively accounting for 34.27% (158/461) and 33.84% (156/461) of the total number of enterprises. Which followed by the Hanjiang, accounting for 23.21% of the total number of enterprises (107/461) ; The monitoring enterprises were mainly distributed in the manufacturing and power industries, which accounted for 85.25% (393/461) and 6.07% (28/461) of the total number of enterprises, respectively. Conclusion: The monitoring rate of enterprises had been increasing year by year from 2014 to 2018. Noise was the main disease prevention and controlling factor in the area.In addition, micro-enterprises, individual economy and foreign-invested economy were the key targets for occupational health.

Abstract: Objective To explore polygraph accuracy of Control Question Test （CQT）and whether it could be influenced by examinee's education level and type of violation of law. Methods Real cases of CQT （ n =104） and the data from MAO （ n =296） were collected. The polygraph accuracy of CQT was calculated. Variance analysis on three groups of different education levels was used to compare their age, and then the chi-square test was employed to compare polygraph accuracy among the groups. Independent sample t test was used to compare the age of subjects in the two groups of different types of violation of law, and then chi-square test was used to compare the true positive rate and true negative rate of lie detection after integration. Results In CQT lie detection of criminal cases, the true positive rate was 87.00%, the false negative rate was 13.00%, the true negative rate was 82.20%, and the false positive rate was 17.80%. There was no statistical significance in the differences between the true positive rate and the true negative rate （ P >0.05）. In CQT lie detection of the groups of different education levels, there was no statistical significance in the differences between the true positive rates （ P >0.05） while the differences between the true negative rates had statistical significance （ P <0.05）. There was no statistical significance in the differences of both the true positive rates and the true negative rates between the violent violation of law and non-violent violation of law （ P >0.05）. Conclusion There is no significant difference between the efficiency of CQT lie detection of identifying criminals and excluding innocents. However, a comparatively high false positive rate and false negative rate still exist. The efficiency of CQT lie detection identifying criminals may not influenced by the examinee's education level and type of violation of law, but its efficiency of excluding innocents may be influenced by the examinee's education level., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

Objective: To analyze the de novo point mutations in known genes among patients with unexplained intellectual disability (ID) or developmental retardation (DD). Methods: A total of 120 outpatients with ID or DD were recruited in the Department of Neurology, Affiliated Children's Hospital of Capital Institute of Pediatrics between September 2015 and April 2017. Target gene sequencing was used to screen the candidate gene. The sequencing data were analyzed by a variety of bioinformatics software. Combining with the phenotypes of the patients, the candidate genetic/genomic variants were identified from next-generation sequencing data. The final pathogenicity of the genetic/genomic variants were interpreted according to the guideline of the American College of Medical Genetics and Genomics (ACMG) for variants after segregation analysis in the parents and necessary family members by Sanger sequencing. The comprehensive physiological function and signaling pathways of 20 disease genes with de novo point mutation discovery was also studied. Results: Among the 120 patients, 23 patients were found to carry clear pathological changes, and the incidence of de novo point variation was 19.2%. The patients included 12 males and 11 females, with an age of 2 months to 6-year-6-month. Five patients were diagnosed with early onset of epileptic encephalopathy. Seven had mental retardation type 5, 6, 8, 19, 20, 22, 39, respectively. Weill-Marchesani syndrome type 2 was found in one case, Wiedemann-Steiner syndrome in one case, Coffin-Siris syndrome in two cases, Rubinstein-Taybi syndrome in one case, GLUT1 deficiency syndrome in one case, Rett syndrome in one case, cardio-facio-cutaneous syndrome 3 in one case, neurodegeneration with brain iron accumulation in one case, corpus callosum local dysplasia in one case, and congenital fibrosis of the extra-ocular muscles in one case. A total of 20 novel mutations were reported in this study. No somatic mutation was found in the samples of 6 patients with mutation and their parents' peripheral blood DNA samples by amplicon-based deep sequencing. This study found that the main disease genes were involved in chromatin remodeling, transcriptional regulation, autophagy body assembly, MAPK signal pathway, DNA methylation, potassium, sodium ion transport, cell skeleton assembly and skeletal muscle development. These genes were significantly enriched in the following biological processes: Ras signaling pathways, transcription factor binding and cancer related signaling pathway. Conclusions: The etiology of children affected with intellectual disability or developmental delay is complex. Harmful de novo point mutation plays an important role in these diseases. Targeted exome/genome sequencing based on the core family is helpful for the molecular diagnosis of patients and the discovery of more genes.

Objective: To evaluate the response of oral melphalan plus high-dose dexamethasone (MDex) for patients with primary light chain amyloidosis (pAL). Methods: Clinical data, hematological and organ responses, and survival of 76 patients with pAL who had received MDex from January 2009 to July 2017 were retrospectively analyzed. Results: Of 76 patients (47 males and 29 females with the median age of 56 [range, 20-74] years old), 19.70% patients were defined as Mayo 2004 stage 3, involvement of more than or two organs was presented in 65 (85.53%) patients. Among 60 response evaluable patients, overall hematological response was 48.33% with complete response of 20.00% and very good partial response of 20.00%, respectively. The median time to the hematological response was 5 (range, 1-15) months. 36.67% patients achieved organ response. After the median follow up of 23(range, 1-113) months for surviving patients, median progression-free survival (PFS) and overall survival (OS) were 34 and 43 months, respectively. In a three months landmark analysis, the median rates of PFS and OS were 46 and 65 months, respectively. The median OS rates of patients with Mayo 2004 stage 3 and non Mayo 2004 stage 3 were 5 and 65 months ( P =0.001), respectively. Conclusions: MDex was an effective treatment for patients with early stage pAL, but was not suitable for those with severe cardiac involvement.

Objective: To evaluate the impact of KIT D816 mutation on the salvage therapy in relapsed acute myeloid leukemia (AML) with t(8;21) translocation. Method: The characteristics of the first relapsed AML with t(8;21) translocation from 10 hospitals were retrospectively collected, complete remission (CR(2)) rate after one course salvage chemotherapy and the relationship between KIT mutation and CR(2) rate was analyzed. Results: 68 cases were enrolled in this study, and 30 cases (44.1%) achieved CR(2). All patients received KIT mutation detection, and KIT D816 mutation was identified in 26 cases. The KIT D816 positive group had significantly lower CR(2) compared with non-KIT D816 group (23.1% vs 57.1%, χ (2)=7.559, P =0.006), and patients with longer CR(1) duration achieved significantly higher CR(2) than those with CR(1) duration less than 12 months (74.1% vs 31.9%, χ (2)=9.192, P =0.002). KIT D816 mutation was tightly related to shorter CR(1) duration. No significant difference of 2 years post relapse survival was observed between KIT D816 mutation and non-KIT D816 mutation group. Conclusion: KIT D816 mutation at diagnosis was an adverse factor on the salvage therapy in relapsed AML with t(8;21) translocation, significantly related to shorter CR1 duration, and can be used for prediction of salvage therapy response. KIT D816 mutation could guide the decision-making of salvage therapy in relapsed AML with t(8;21) translocation.

Objective: To evaluate the clinical characteristics, diagnosis criteria, treatment and prognosis in patients with Bing-Neel Syndrome (BNS) . Methods: The clinical characteristics, lab data, treatment and outcomes of 3 Bing-Neel syndrome patients diagnosed at Peking Union Medical College Hospital were collected. Results: The clinical presentation was heterogeneous without any specific common signs or symptoms. One patient was diagnosed with BNS 42 months after diagnosis of Waldenström macroglobulinemia (WM) by cerebrospinal fluid (CSF) cytology and flow cytometry, but dead of infection during the first course of chemotherapy. BNS was the first manifestation of WM in the other 2 cases. They were diagnosed by flow cytometry and cytology of CSF. The detection of MYD88(L)265P mutation in CSF contributed to diagnosis and to sequential monitoring of minimal residual disease. They received systemic chemotherapy of FC (fludarabine + cyclophosphamide) ± rituximab and intrathecal therapy, followed by maintenance therapy of chlorambucil or R2 (rituximab + lenalidomide) . They were followed 17 and 20 months respectively without progression of disease. Conclusion: The diagnosis approach of BNS should be based on a combination of CSF cytology, flow cytometry and detection of the MYD88(L265P) mutation. The detection of MYD88(L265P) mutation may be useful in the monitoring of minimal residual disease.