Hyperphenylalaninemia is a common group of inherited metabolic diseases.It is characterized by the increased concentration of plasma phenylalanine.The metabolism of phenylalanine requires phenylalanine hydroxylase and coenzyme tetrahydrobiopterin.These enzymes cannot function normally if there is any mutation in their encoding genes.Children suffering from hyperphenylalaninemia without promptly treatment may present mental development delay and other serious nervous system sequelae.With the technical improvement of molecular genetics,there have been many progresses in the study of genetic diagnosis,genotype-phenotype correlation and gene therapy of hyperphenylalaninemia.This article reviews the history and classification of hyperphenylalaninemia,the characteristics of gene mutation,the methods of genetic diagnosis,the genotype-phenotype correlation,and the progress of new therapy.

SUMMARY Anaphylaxis is an acute and fatal systemic allergic reaction to an allergen , and it could be an unpre-dictable and life-threatening cause during anesthesia .The main purpose of this paper is to report a case of anaphy-lactic shock during the anesthesia induction and to review the prophylaxis and treatment of anaphylactic reactions and anaphylactoid reactions during the anesthesia period .A 63-year-old man, with a mass on his adrenal , was scheduled to a laparoscopic adrenal tumor excision .During the anesthesia induction period , after administrated sul-fentanil, propofol and rocuronium , the blood pressure was decreased and the heart rate was increased .Then, the patient had rash on his whole body and developed an anaphylactic shock .After being treated with the anti-allergic agents and norepinephrine , the rash disappeared and the vital sign become stable .The patient felt nothing uncom-fortable during the two weeks ’ follow-up.Anaphylactic reactions and anaphylactoid reactions are not rare during the anesthesia period .The most common inducements are muscle relaxant , latex and antibiotics .Anaphylactic reac-tions in the perioperative period are often serious and potentially life-threatening conditions , involving multiple or-gan systems in which the clinical manifestations are the consequence of the release of preformed mediators from mast cells and basophils .Before anesthesia , we should acquire the allergic history .During the anesthesia period , the vi-tal sign and the skin should be observed carefully .

[Summary] The clinical and genetic characteristics of a patient with male pseudohermaphroditism, being considered as an isolated 17, 20-lyase deficiency case, were analyzed. The social gender of the patient aged 30-year-old was female. The patient presented with 46, XY karyotype, unclosed epiphysis, after perineal block resection, hypergonadotropic hypogonadism, while the production of mineralocorticoids and glucocorticoids hormone was intact. A503V heterozygous mutation in exon 13 and a deletion in intron 11 of POR gene were detected. The gene mutations may lead to the occurrence of the isolated 17,20-lyase deficiency.

OBJECTIVETo analyze the features of genetic mutations underlying Wilson's disease and provide prenatal and presymptomatic diagnosis.

METHODSFor 35 pedigrees affected with the disease, the exons and exon-intron boundaries of the ATP7B gene were amplified with polymerase chain reaction and subjected to Sanger sequencing. After the genotypes of parents of the probands were determined, prenatal diagnosis were performed through chorionic villus sampling.

RESULTSThe overall rate for mutation detection was 92.9%. A total of 24 distinct mutations were detected, which included 7 novel mutations, i.e., c.3871G>A(p.A1291T), c.2593_2594insGTCA, c.2790_2792delCAT, c.3661_3663delGGG, c.3700delG, c.4094_4097delCTGT, and IVS6+1G>A. Three mutations, including R778L (c.2333G>T)(45.7%), A874V (c.2621C>T)(7.1%) and P992L (c.2975C>T)(7.1%), were relatively common. Two presymptomatic patients were detected through familial screening, for whom treatment was initiated. Prenatal genetic diagnosis has verified three healthy fetuses and one carrier.

CONCLUSIONIn this study the most popular mutation ofATP7B gene is R778L and 7 novel mutations have been identified in this gene. For pedigrees of Wilson's disease, genetic counseling in addition with prenatal and presymptomatic diagnosis should be provided through Sanger sequencing and haplotype analysis.

Adenosine Triphosphatases ; genetics ; Adult ; Base Sequence ; Cation Transport Proteins ; genetics ; Copper-transporting ATPases ; DNA Mutational Analysis ; Female ; Genotype ; Hepatolenticular Degeneration ; embryology ; enzymology ; genetics ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation ; Pedigree ; Pregnancy ; Prenatal Diagnosis

CRISPR/Cas9 technology originated from type II CRISPR/Cas system, which is widely found in bacteria and equips them with acquired immunity against viruses and plasmids. CRISPR-associated protein Cas9 is a RNA-guided endonuclease, which can efficiently introduce double-strand breaks at specific sites and activate homologous recombination and/or non-homologous end joining mechanism for the repair of impaired DNA. Features such as easy-to-use, cost-effectiveness, multiple targeting ability have made it the third-generation genomic engineering tool following ZFNs and TALENs. Here the history of discovery and molecular mechanism of the CRISPR/Cas9 technology are reviewed. The rapid advance in its various applications, especially for the treatment of human genetic disorders, as well as some concomitant problems are discussed.
Biomedical Research ; methods ; trends ; CRISPR-Cas Systems ; genetics ; Gene Editing ; methods ; Genome, Human ; genetics ; Humans ; Models, Genetic ; Reproducibility of Results

Objective: To describe the epidemiological characteristics and clinical manifestations of the 2019 coronavirus disease (COVID-19) in pediatric patients, and to provide data support and decision-making basis for the prevention and control of COVID-19. Methods: Cases of children aged 0-17 years reported by provincial health commissions in Anhui, Shandong, Zhejiang and Henan provinces were collected to analyze their spatial, temporal, and demographic distribution. Results: By 24:00 on February 6, 2020, a total of 107 pediatric patients had been reported in the four provinces, accounting for 3.8% (107/2 808) of the total cases reported in the four provinces during the same period. Anhui, Shandong, Zhejiang and Henan provinces had 25, 25, 28 and 29 cases, respectively. Cases ranged in age from 5 days after birth to 17 years, with a median age of 8 years. Boys accounted for 58.9%. Totally 38 cases had a history of sojourn in Wuhan or Hubei, 63 cases had a history of exposure to confirmed cases, and 6 cases with unknown exposure history. A group of 52 family clustering were found in 107 cases. All cases presented mild symptoms, no serious and no death. Conclusion Children were also susceptible to the COVID-19. Before February 2, the index pediatric cases were mainly the first generation cases, and after February 3, these pediatric cases were mainly the secondary-generation cases and those who had close contact with confirmed cases. The monitoring of children with secondgeneration cases and close contact with COVID-19 cases were valued.

Objective:To investigate the optimal angle of bedhead elevation during logrolling of patients with severe stroke supported by continuous enteral nutrition via gastric tube administration, and to provide a basis for safe infusion of enteral nutrition in clinical practice.Methods:This study was a prospective study, and the repeated measurement method was used. A total of 154 patients with severe stroke who were admitted to the Neurology Intensive Care Unit of the the 960th Hospital of the Joint Logistic Support Force of the Chinese People′s Liberation Army and treated with continuous enteral nutrition support from January to October 2023 were selected as the study participants by convenience sampling method. The times and duration of cardia reflux in 5 min were observed under ultrasound when the bedhead elevation angle during logrolling of the study participants was 30°, 20°, 10°, and 0°, respectively, and the incidence of reflux and aspiration during the observation period were recorded.Results:A total of 148 patients were eventually included. Among them, 81 were males and 67 were females, aged 38-80 (65.79 ± 10.96) years. There were no significant differences in the incidence of reflux [18.24% (27/148) vs. 12.16% (18/148)] and aspiration [4.05% (6/148) vs. 1.35% (2/148)] when the angle of bedhead elevation during logrolling of patients with continuous enteral nutrition via gastric tube administration was 10° and 20° (all P>0.05). Nevertheless, compared with the incidence of reflux [37.16% (55/148)] and aspiration [(10.81% (16/148)] at the bedhead elevation angle of 0°, those measured at 10° or 20° were significantly different ( χ2 values were 4.91-24.89, all P<0.05). Conclusions:For patients with severe stroke supported by continuous enteral nutrition, bedhead elevation angle of 10° can not only prevent aspiration caused by gastric reflux, but also conform to the labor-saving principle during logrolling, which is the recommended angle of logrolling for patients with severe neurological diseases supported by continuous enteral nutrition.

Bispecific antibodies, that are the second generation of new type of antibodies with two specific antigens or epitopes binding sites, can combine with target cells and effector cells (or molecules) at the same time. The recent studies demonstrated that Bispecific antibodies possess the immense therapeutic potential for cancer, ASID and autoimmune diseases. In this review, the various targets and function, the underlying mechanisms, and the application progress of Bispecific antibodies in cancer therapy were discussed.

Objective: To compare the anesthetic effects of subarachnoid anesthesia(SA)and epidural anesthesia(EA)for the procedure for prolapse and hemorrhoids(PPH)in elderly patients with benign anorectal diseases. Methods: A retrospective analysis was conducted in 60 patients with benign anorectal diseases admitted to Peking University Third Hospital from March to August 2018 and undergoing PPH.According to anesthesia methods, patients were divided into the SA group and the EA group (n=30 each). The level of sensory block was tested by acupuncture, and the degree of motor block was assessed by revised Bromage score.The anesthesia effect, operation time, blood loss, adverse events and hospitalization time were compared between the two groups. Results: The highest level of sensory block was similar between the two groups without significant difference(P>0.05). The median onset time of sensory block was longer in the EA group [270.0 s(interquartile range, 66.3 s)] than in the SA group [25.5 s(interquartile range, 14.3 s)]. The revised Bromage score was lower in the EA group than in the SA group [1.0(interquartile range, 1.0)vs.2.0 (interquartile range, 1.0), Z=6.657, -1.685, both P=0.000]. The risks of hypotension, nausea and vomiting, and urinary retention were lower in the EA group than in the SA group (χ²=6.405, 4.286 and 4.403, P=0.011, 0.038 and 0.044). There were no significant differences in anesthetic effect, operation time, blood loss and hospitalization time between the two groups(all P>0.05). Conclusions EA can provide a perfect anesthesia and analgesic effect for elderly patients receiving PPH, with the advantages of rapid recovery of limb movement and low adverse events.As a substitute for SA, EA is a suitable anesthesia method for promoting the enhanced recovery after surgery(ERAS)in patients with benign anorectal diseases.

We used the epidemic data of COVID-19 published on the official website of the municipal health commission in Anhui province. We mapped the spatiotemporal changes of confirmed cases, fitted the epidemic situation by the population growth curve at different stages and took statistical description and analysis of the epidemic situation in Anhui province. It was found that the cumulative incidence of COVID-19 was 156/100 000 by February 18, 2020 and the trend of COVID-19 epidemic declined after February 7, changing from J curve to S curve. The actual number of new cases began to decrease from February 2 to February 4 due to the time of case report and actual onset delayed by 3 to 5 days.