Objective To explore the effects of isoflurane on blood plasma metabolites (BPM) and its correlation with cognitive dysfunction.Methods Thirty female Sprague-Dawley (SD) rats were randomly divided into two groups:rats in the control group (n =10) received 80％ oxygen for 2 hours (h);and rats in the isoflurane-treated group (n =20) were anesthetized with isoflurane and 80％ oxygen for 2 h.Cognitive functions were examined using a Y-maze test to explore the learning times of rats.The level of blood plasma metabolites was detected through gas chromatography-mass spectrometry (GCMS).Results The learning times of rats in the isoflurane-treated group was more than the learning times of rats in the control group [(70.75 ± 15.30) vs (45.40 ± 11.21),P ＜ 0.05].D-fructose,arabinofuranose,n-butylamine,and inositol significantly increased (P ＜ 0.05),respectively.Whereas,L-analine and L-proline significantly decreased (P ＜ 0.05) in isoflurane-treated rats when compared to those in the control rats (P ＜ 0.05).Moreover,plasma concentrations of d-fructose,arabinofuranose,n-butylamine,inositol,and L-proline were positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats.Conclusions Changes of plasma concentrations of inositol,and d-fructose in aged rats are useful in predicting the occurrence and progression of post-anesthesia cognitive dysfunction.

ObjectiveTo explore the screening and therapeutic efficacy of primary carnitine deficiency (PCD) in newborns and mothers.Methods164245 newborns and suspected mothers were investigated for PCD by tandem mass spectrometry (MS/MS).The overall epidemiology,prognosis,and follow-up of the screening program were investigated.ResultsTotally 55 suspected cases were identified at the primary screening stage.Four newborns and three mothers were confirmed as cases of PCD.The incidence rate of newborns was 1 ∶ 40076.All the patients showed normal growth and development during the follow-up.Blood free carnitine level was raised in all three mothers after treatment.ConclusionsScreening for PCD with MS/MS in newborns may represent a valuable procedure in preventive medicine by enabling early diagnosis and treatment before the onset of symptoms.This protocol is also highly efficient and applicable in diagnosis of mothers with PCD.

Objective To explore the methods, dosimetric features and short-term effects of partial breast irradiation carried out by three-dimensional external-beam irradiation (3DCPBI) assisted by active breathing control (ABC) . Methods Computed tomography (CT) simulation assisted by active breathing control (ABC) was carried out for each patient and intended to get CT images in condition of 75% deepest inspiration named moderate deep inspiration breath hold (mDIBH). The extent labeled by the silver slips located in the cavity was delineated as gross target volume (GTV) , GTV plus the margin of 15 mm was defined as planning target volume (PTV). 6 MV X-ray was selected as the radiation source and noncoplanar radiation with four three-dimensional conformal fields was used, the described dose was 34 Gy /10f/5d. The volume of GTV, PTV, the affected whole breast, and the percentage of PTV accounted for the affected whole breast , the percentages of PTV included by 100% , 95% and 90% isodose curve, the percentage of volume of the affected breast irradiated by 34. 0, 27. 2, 20. 4, 13. 6 and 6. 8 Gy , and Dmean,D5,V20 of the lungs and heart were calculated respectively. Acute radiation skin response was recorded and the cosmetic effect of the breast after radiotherapy were appraised, with the local tumor control and survival rate followed. Results The mean of volume ratio of PTV and affected whole breast was 14. 88% ; the mean of the volume covered by 90% isodose curve accounted for 92. 54% of the PTV; the volume irradiated by 34 Gy (100% of described dose) accounted for 17. 23% (mean) of the whole breast and 6. 8 Gy (20% of described dose) for 46. 11% , in other words, the volume covered by 20% of described dose was less than 50% of the whole breast. The Dmean, D5, V20 for the affected lateral lung were 1.97, 9. 25 Gy and 1. 58% , it was 0.20, 0. 87 Gy , and 0% for the unaffected lateral lung. The Dmean,D5, V20 for the heart was 0.65 Gy , 2. 82 Gy , and 0. 85%. Zero grade of acute radiation skin reaction was seen in 14 patients and gradel in 3 patients and there was not equal to or more than grade 2 of skin reaction for all the patients. Cosmetic effect were appeci-ated and satisfaction defined as excellent or good appearance of the irradiated breasts for all the patients. No recurrence of local tumor for all of the patients followed for one year. Therefore, the cosmetic result of 1 yr. follow - up was 100% and no recurence was found after 1 yr. follow - up. The 1-year tumor-free survival rate were all 100%. Conclusions For selected patients with early breast cancer after breast-conservative surgery, 3DCPBI assisted by ABC is feasible, however, the selection criteria for the patients, technique protocol and dose fractionation of 3DCPBI and its influence on late cosmetic effect, local tumor control and survival need to be continuously explored and observed in the future.

Amino Acid Metabolism, Inborn Errors ; diagnosis ; genetics ; therapy ; Death, Sudden ; etiology ; Hereditary Central Nervous System Demyelinating Diseases ; diagnosis ; etiology ; Humans ; Hydroxymethylglutaryl-CoA Synthase ; deficiency ; Infant, Newborn ; Male ; Mutation ; Oxo-Acid-Lyases ; genetics ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

Objective:To evaluate the curative effects of 3D printed microporous titanium (tantalum) prosthesis in reconstruction of large segmental bone defects caused by lower extremity osteomyelitis.Methods:A retrospective study was conducted to analyze the clinical data of 18 patients who had been treated for large segmental bone defects caused by lower extremity osteomyelitis between January 2020 to May 2022 at Department of Orthopaedics, The 920th Hospital of Joint Logistics Support Force. There were 10 males and 8 females with an age of (45.3±14.1) years. The defects were at the left side in 13 cases and at the right side in 5 cases, at the femur in 11 cases and at the tibia in 7 cases. The duration of osteomyelitis was 1.0 (1.0, 3.5) years. The length of bone defects was 8.35 (6.50, 9.84) cm. Their bone defects were repaired by an individually 3D printed microporous titanium (tantalum) prosthesis after operative removal of osteomyelitis lesions. The wound healing was observed after surgery. The clinical efficacy was comprehensively evaluated by the Paley grading for bone defect healing, visual analog scale (VAS), lower extremity functional scale (LEFS), and imaging examination.Results:The postoperative follow-up period for the 18 patients was (12.2±0.3) months. Wound infection occurred 2 months after surgery in one patient who was treated with Ilizarov bone transfer after removal of the microporous titanium prosthesis. The remaining 17 patients had good postoperative wound healing. At the last follow-up, the 18 patients had a VAS pain score of 2.0(1.0, 4.0) points, significantly lower than the preoperative one [(6.1±2.3) points], and a LEFS score of 54.00(34.50, 69.25) points, significantly higher than the preoperative one [18.50(9.00, 26.50) points] ( P<0.05). At the last follow-up, according to the Paley grading, the bone union was rated as excellent in 16 patients, as good in 1 patient and as poor in 1 patient. The integration of femoral fractures with 3D printed microporous titanium prostheses was fine. Conclusion:In reconstruction of large segmental bone defects caused by lower extremity osteomyelitis, implantation of a 3D printed microporous titanium (tantalum) prosthesis is feasible and effective, not only reducing pain but also restoring the limb function.

Objective:To investigate the efficiency of biochemical screening and hotspot gene screening in the detection of neonatal inherited metabolic diseases.Methods:This was a prospective multi-center study.The study was carried out on 21 442 neonatal samples collected from 12 hospitals in 10 provinces from November 2020 to November 2021.The results of biochemical screening and hotspot gene screening were analyzed jointly.Biochemical screening methods included glucose-6-phosphate dehydrogenase deficiency enzyme activity assay and neonatal tandem mass spectrometry.Genetic screening analysis involved 135 genes associated with 75 neonatal diseases.Results:Of all the 21 442 neonates enrolled in the study, 21 205 were subject to biochemical screening.A total of 813 cases were positive in the initial screening, and 0.45% of them (95 cases) were diagnosed after recall.All the 21 442 neonates underwent gene screening.About 168 positive cases were detected in the initial screening, and 0.73% (156 cases) of them were confirmed finally.Biochemical and genetic screening improved the detection sensitivity of such diseases as primary carnitine deficiency, neonatal intrahepatic cholestasis caused by citrin deficiency, and 2-methylbutyrylglycinemia.Moreover, biochemical and genetic screening enabled the detection of more diseases, including the common single-gene genetic diseases such as thalassemia and Wilson disease.Conclusions:In neonatal screening, the combination of biochemical screening and gene screening expands the number of diseases detected and improve screening efficiency.

Objective:To investigate the incidence, clinical characteristics and prognosis of ornithine transcarbamylase deficiency(OCTD) in newborns in Zhejiang Province.Methods:A retrospective research was conducted.A total of 4 261 036 newborns from Department of Genetics and Metabolism, Children′s Hospital, Zhejiang University School of Medicine, between January 2009 and December 2021 were screened for inherited metabolic disorders using tandem mass spectrometry.OCTD was confirmed by urine organic acid and OTC gene analysis.Patients with OTCD received guidance on diet and lifestyle management, and were treated with citrulline and arginine.Long-term follow-up was performed.Their growth and intellectual development were evaluated. Results:A total of 7 patients with OCTD were diagnosed, with an incidence of 1.6/1 million.All patients were males.Two patients had neonatal-onset OCTD, and the other 5 had late-onset OCTD.Symptoms occurred several times in 6 patients, inducing hyperammonemia and hepatic impairment.One patient had no clinical manifestation.One patient died in the neonatal period.Blood citrulline levels were decreased in 7 patients to varying degrees.Uracil levels were increased in 4 patients, and 1 of them was complicated with elevated orotic acid levels.All patients had hemizygote variations in the OTC gene, including 6 missense variations(c.604C>T, c.386G>A, c.779T>C, c.1019C>T, c.594C>G, c.931G>A) and 1 intron variation(c.514-35C>G). Two variants(c.594C>G, c.514-35C>G) were never reported previously. Conclusions:The OTCD incidence by newborn screening is low with 1.6/1 million in Zhejiang province.All patients are males and present hypocitrullinemia.The clinical manifestations of OTCD are highly heterogeneous.The neonatal-onset form is severe and survivors always suffer serious sequelae.The late-onset form is mostly manifested with hyperammonemia and hepatic impairment.There may be association between phenotype and genotype.Two novel OTC variants are identified, which further expands the mutational spectrum.

OBJECTIVE: To investigate the genetic characterization of 3-hydroxyisovalerylcarnitine (C5-OH) metabolic abnormality in neonates. METHODS: Fifty two newborns with increased C5-OH, C5-OH/C3 and C5-OH/C8 detected by tandem mass spectrometry during neonatal screening were enrolled in the study. Genomic DNA was extracted from the whole blood samples of 52 cases and their parents. Seventy-nine genes associated with genetic and metabolic diseases including , were targeted by liquid capture technique. Variation information of these genes was examined by high-throughput sequencing and bioinformatic analysis, and then was classified based on the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. The genetic types were classified as wild-type, -maternal-mutation, -paternal-mutation and -mutation. Wilcoxon rank-sum test was performed for the increased multiples of C5-OH calculated in neonatal screening. RESULTS: Twenty one variants (14 novel) were identified in 37 cases, 6 variants (5 novel) in 4 cases. The increased multiple of C5-OH calculated in -maternal-mutation and -mutation groups were significantly higher than that in wild-type group (all <0.05), while there was no significant difference between MCCC1-paternal-mutation group and wild-type group (>0.05). CONCLUSIONS Mutations on and genes are the major genetic causes for the increased C5-OH in neonates, and maternal single heterozygous mutation can contribute to the moderately to severely increased C5-OH.
Carbon-Carbon Ligases ; genetics ; Carnitine ; analogs & derivatives ; metabolism ; Female ; Genetic Testing ; Genetic Variation ; Humans ; Infant, Newborn ; Male ; Mutation ; Neonatal Screening ; Urea Cycle Disorders, Inborn ; genetics

Colorectal cancer is one of the most common malignant tumors of digestive tract. In 2020， 1.93 million new cases of colorectal cancer were diagnosed globally， ranking third in the global incidence spectrum， and 930 000 new deaths were reported， ranking second in the global cause of death spectrum. Meanwhile， the medical cost of metastatic colorectal cancer is the highest among all stages. A large number of studies have demonstrated that traditional Chinese medicine（TCM） treatment can bring clinical benefits to patients with metastatic colorectal cancer with unique efficacy. In order to further standardize the TCM diagnosis and treatment for metastatic colorectal cancer and improve the level of TCM diagnosis and treatment， Xiyuan Hospital， China Academy of Chinese Medical Sciences， together with other relevant units in China， according to the guideline development process of the World Health Organization Handbook for Guideline Development and the relevant requirements of the Clinical Evidence Grading Criteria on TCM Based on Evidence Body， the Regulations for Group Standards of China Association of Chinese Medicine and others， combined with the characteristics of TCM diagnosis and treatment and the actual situation in China， the Guidelines for TCM Diagnosis and Treatment of Metastatic Colorectal Cancer was developed in accordance with the Catalogue of TCM Diagnosis and Treatment Plans for 105 Diseases in 24 Specialties issued by Department of Medical Administration of National Administration of TCM.

OBJECTIVETo screen fatty acid oxidation disorders (FAOD) in newborns in Zhejiang province.

METHODSA total of 1 861 262 newborns were screened for FAOD in Neonatal Screening Center of Zhejiang Province during January 2009 and December 2016. The blood samples from newborns were screened by tandem mass spectrometry, and diagnosis of FAOD was confirmed by urine organic acid measurement combined with genetic analysis. The prognosis and follow-up of patients with FAOD were also evaluated.

RESULTSOf 1 861 262 newborns screened, 121 cases of FAOD were diagnosed. Among 121 cases of FAOD, primary carnitine deficiency (PCD) was the most common type (=78, 64.5%), which was followed by short-chain acyl-CoA dehydrogenase deficiency (SCADD,=27, 22.3%), medium-chain acyl-CoA dehydrogenase deficiency (=5, 4.1%), multiple acyl-CoA dehydrogenase deficiency (MADD,=4, 3.3%), very long-chain acyl-CoA dehydrogenase deficiency (=3, 2.5%), carnitine palmitoyltransferase Ⅰ deficiency(=2, 1.7%)and carnitine palmitoyltransferase Ⅱ deficiency (CPTⅡD,=2, 1.7%). During 2-82 month follow-up, 15 patients were lost, 4 were dead (1 PCD, 1 MADD, and 2 CPTⅡD), and the remaining 102 subjects had normal intelligence and physical development without any clinical symptoms.

CONCLUSIONSPCD and SCADD are the most common FAODs in newborns in Zhejiang province. Most of FAOD patients are asymptomatic, and have normal growth and development after early intervention and management.