Objective:To explore the characteristics and influencing factors of blood carnitine metabolism in premature infants.Methods:A retrospective analysis of 37 037 neonates with negative results of genetic metabolic disease screening at Guangxi Newborn Disease Screening Center from 2018 to 2021, of which 34 517 normal full-term infants were the control group and 2 520 preterm infants were the research group.According to gestational age, the preterm infants were further divided into three groups: extremely preterm group( n=232), moderately preterm group( n=324)and late preterm group( n=1 964). According to birth weight, they were divided into three groups: very low birth weight group( n=188), low birth weight group( n=1 276)and normal birth weight group( n=1 056). According to blood collection time, they were divided into three groups: 3~7 days group( n=1 990), 8~14 days group( n=342) and 15~28 days group( n=188). Tandem mass spectrometry was used to detect the levels of 31 carnitines in dried blood spots and analyze the differences in the levels of metabolic indicators in each group. Results:Carnitine levels in preterm infants are most affected by gestational age.Adjusting the physiological and pathological conditions of premature infants and other related factors, grouped by gestational age, there were differences in the levels of 31 carnitines among the groups(all P<0.05), the smaller the gestational age, the greater the difference in carnitine levels; grouped by blood collection time, there were statistically significant differences in carnitine levels between preterm infants with different blood collection age groups and full-term 3~7 days groups(all P<0.05), and showing age-related; there are differences among 31 carnitines grouped by body weight(all P<0.05), the smaller the body weight, the greater the difference in carnitine levels.Combined with the analysis of gestational age, birth weight and blood collection date, 17 indicators including C0, C2, C3, C4, C6DC, C10, C10∶1, C12, C12∶1, C14, C14∶1, C14OH, C16, C16∶1, C18, C18∶1 and C18∶1OH are important biomarkers of carnitine metabolism in premature infants. Conclusion:Carnitine in premature newborns has different metabolic differences at different gestational ages, birth weights and blood collection ages, which provides a strong basis for establishing reference standards and interpretation of preterm infants in the laboratory in this region, and provides reasonable and effective early diagnosis and treatment for clinical practice.Meanwhile, it provides an optimized program for timely detection of carnitine deficiency and carnitine supplementation to improve nutrition of premature infants.

OBJECTIVE: To analyze the metabolic profile and genetic variants for newborns with primary carnitine deficiency (PCD) from Guangxi, China. METHODS: From January 2014 to December 2019, 400 575 newborns from the jurisdiction of Guangxi Zhuang Autonomous Region Newborn Screening Center were subjected to tandem mass spectrometry (MS/MS) analysis. Newborns with positive results for PCD and their mothers were recalled for retesting. Those who were still positive were subjected to sequencing of the SLC22A5 gene. RESULTS: Twenty-two newborns and 9 mothers were diagnosed with PCD, which gave a prevalence rate of 1/18 208. Sequencing of 18 newborns and 4 mothers have identified 14 types of SLC22A5 gene variants, with the common ones including c.51C>G (10/44, 22.7%), c.1195C>T (9/44, 20.5%) and c.1400C>G (7/44, 15.9%), The c.517delC(p.L173Cfs*3) and c.1031C>T(p.T344I) were unreported previously and predicted to be pathogenic (PVS1+PM2_supporting+PM3+PP4) and likely pathogenic (PM1+PM2_supporting+PM3+PP3+PP4) based on the American College of Medical Genetics and Genomics standards and guidelines. CONCLUSION c.51C>G, c.1195C>T and c.1400C>G are the most common variants underlying PCD in Guangxi.
Cardiomyopathies ; Carnitine/deficiency* ; China ; Humans ; Hyperammonemia ; Infant, Newborn ; Metabolome ; Muscular Diseases ; Mutation ; Solute Carrier Family 22 Member 5/genetics* ; Tandem Mass Spectrometry

Objective: To explore the clinical application value of enhanced recovery after surgery (ERAS) in the laparoscopic surgery for cholecystolithiasis comorbid with choledocholithiasis. Methods: The prospective study was conducted. The clinicopathological data of 52 patients with cholecystolithiasis comorbid with choledocholithiasis who were admitted to the Third Affiliated Hospital of Zunyi Medical University from September 2016 to September 2018 were collected. Patients were divided into 2 groups by random number table: patients in observation group received laparoscopic cholecystectomy + choledocholithotomy + choledochoscopic exploration + T-tube drainage (or primary suture of common bile duct) and perioperative management guided by the concept of enhanced recovery after surgery (ERAS), and patients in control group received traditional perioperative management. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) postoperative complications; (4) postoperative pain scores; (5) changes in hepatic function and blood routine during perioperative period. Follow-up using outpatient examination and telephone interview was performed to detect complications during the postoperative 6 months up to March 2019. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using the paired t test or repeated ANOVA. Count data were described as absolute numbers and percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Results: Fifty-two patients were screened for eligibility, including 20 males and 32 females, aged 25-68 years, with an average age of 53 years. There were 30 patients in the observation group and 22 in the control group. (1) Surgical situations: the operation time and volume of intraoperative blood loss were (133±19)minutes and (47±21)mL in the observation group, and (136±22)minutes and (49±23)mL in the control group, respectively, showing no significant difference between the two groups (t=-0.386, -0.211, P>0.05). (2) Postoperative situations: time to out-of-bed activity, time to initial food intake, time to first anal flatus, duration of postoperative hospital stay, and hospital expenses were (18±4)hours, (19±5)hours, (28±2)hours, (4.0±1.0)days, and (1.82±0.22)×10⁴ yuan in the observation group, and (29±7)hours, (46±9)hours, (37±4)hours, (6.6±1.6)days, and (2.25±0.29)×10⁴ yuan in the control group, respectively, showing significant differences between the two groups (t=-7.054, -14.169, -9.426, -6.582, -5.809, P<0.05). (3) Postoperative complications: 1 of 30 patients in the observation group had postoperative biliary leakage, with a postoperative complication rate of 3.3%, and was cured after symptomatic support treatment. Six of 22 patients in the control group had postoperative complication, with a postoperative complication rate of 27.3%, including 2 of biliary leakage, 1 of hemorrhage, 1 of abdominal infection, 1 of pulmonary infection, 1 of urinary infection, and they were cured after symptomatic support treatment. There was a significant difference between the two groups (χ²=4.358, P<0.05). (4) Postoperative pain scores: from postoperative 6 hours to 48 hours, the postoperative pain score changed from 2.4±0.7 to 1.9±0.9 in the observation group, and from 4.1±0.7 to 2.9±0.9 in the control group, respectively, showing a significant difference in the changing trend between the two groups (F=78.053, P<0.05). (5) Changes in hepatic function and blood routine during perioperative period: from preoperation to postoperative 3 days, levels of alamine aminotransferase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT), total bilirubin (TBil), and count of white blood cells in the observation group changed from (77±20)U/L to (53±12)U/L, from (85±22)U/L to (61±17)U/L, from (166±39)U/L to (55±24)U/L, from (40±13)μmol/L to (29±12)μmol/L, from (7.0±2.0)×10⁹/L to (6.8±1.9)×10⁹/L, and changed from (79±23)U/L to (62±14)U/L, from (88±24)U/L to (64±17)U/L, from (179±34)U/L to (74±29)U/L, from (45±13)μmol/L to (35±12)μmol/L, from (7.9±2.4)×10⁹/L to (7.5±1.9)×10⁹/L in the control group, respectively. The levels of ALT, AST, GGT, TBiL, and count of WBC showed increasing at postoperative 1 day, and decreasing at postoperative 3 days. There was no significant difference in the changing trend between the two groups (F=0.058, 0.471, 3.021, 1.593, 2.172, P>0.05). Conclusion ERAS is safe and effective in the laparoscopic surgery for choledocholithiasis comorbid with cholecystolithiasis.

In previous studies, we found that truncated rotavirus VP4* (aa 26-476) could be expressed in soluble form in Escherichia coli and confer high protection against rotavirus in the mouse mode. In this study, we further improved the immunogenicity of VP4* by polymerization. The purified VP4* was polymerized through incubation at 37 ℃ for 24 h, and then the homogeneity of the particles was analyzed by HPLC, TEM and AUC, while the thermal stability and antigenicity was analyzed by DSC and ELISA, respectively. Finally, the immunogenicity and protective efficacy of the polymers analyzed by a mouse maternal antibody model. The results showed that VP4* aggregated into homogeneous polymers, with high thermostability and neutralizing antibody binding activity. In addition, VP4* polymers (endotoxin <20 EU/dose) stimulated higher neutralizing antibodies and confer higher protection against rotavirus-induced diarrhoea compared with the VP4* trimers when immunized with aluminium adjuvant. In summary, the study in VP4* polymers provides a new strategy for the development of recombinant rotavirus vaccines.
Animals ; Antibodies, Viral ; Antigens, Viral ; Capsid ; Capsid Proteins ; Mice ; Polymerization ; Rotavirus ; Rotavirus Infections

Objective To investigate the characteristics of the phenylalanine hydroxylase( PAH)gene muta﹣tions in patients With phenylketonuria(PKU)in Guangxi region,in order to provide clinical data for genetic counseling and prenatal gene diagnosis. Methods Thirty－seven children diagnosed as PKU in the Maternal and Children＇s Hos﹣pital of Guangxi Zhuang Autonomous Region Were enrolled in the study betWeen January 2009 and December 2017. Ve﹣nous blood Was collected and the PAH gene sequence Was determined by Sanger sequencing after amplification With the polymerase chain reaction technique. The neW gene mutations Were defined based on the national and international literature revieW and databases. MeanWhile,100 healthy individuals Were selected as the control group for gene sequen﹣cing to confirm Whether the mutation Was a neW one. Results Thirty－seven cases of PKU Were detected for 68 muta﹣tions,With the detection rate being 91. 89%(68／74). Six mutations Were identified in exon 7,Which accounted for 31. 08% of all,exon 12(18. 92%),exon 8(10. 81%)and exon 6(10. 81%)folloWed. A total of 25 different muta﹣tions Were identified Which including 14 missense mutations(56. 00%),7 nonsense mutations(28. 00%),3 splicing junction mutations(12. 00%),and 1 deletion mutation(4. 00%). The most common mutations included c. 1223G＞A (p. R408Q),c. 728G＞A(p. R243Q)and c. 721C＞T( p. R241C),accounting for 14. 86%,13. 51%,and 10. 81%, respectively. After querying international databases,including PAH mutation database and Human Gene Mutation Data﹣base and forecasting softWare,three kinds of mutations c. 314C＞ T(p. T105I),c. 583A＞ G(p. K195E),c . 851G＞A(p. C284Y)Were verified as novel PAH gene mutations. Conclusions The mutation spectrum of the PAH gene in Guangxi has been identified. And 3 kinds of mutations have been identified. This may accumulate valuable information for gene diagnosis and prenatal diagnosis of PKU in Guangxi region.

Objective: To investigate the clinical, biochemical and genetic features of four carnitine-acylcarnitine translocase deficiency cases. Methods: Four cases diagnosed with carnitine-acylcarnitine translocase deficiency from Guangxi Maternal and Child Health Hospital were studied. DNA was extracted from dry blood filter for gene analysis. SLC25A20 gene analysis was performed in 1 case and the whole exon sequence analysis was performed in 3 cases. Results: Retrospective study on unrelated carnitine-acylcarnitine translocase deficiency patients, the age of onset was 1-28 d, the age of death were 1.5-30 d, main clinical features were hypoglycemia (4 cases), arrhythmia (2 cases), sudden death (2 cases). Biochemical test showed hypoglycemia (1.2-2.0 mmol/L) , elevated creatine kinase (955-8 361 U/L) and creatine kinase isozyme(199-360 U/L), normal or decreased free carnitine level (3.70-27.07 μmol/L) , elevated long-chain acylcarnitine (palmityl carnitine 1.85-14.84 μmol/L). The gene tests showed that all 4 cases carried SLC25A20 gene c.199-10T> G homozygous mutation, inherited from their parents. By analyzing the haplotype, we found that the mutation loci of C. 199-10T> G were all in the same haplotype. Conclusion The c.199-10T> G mutation is an important molecular cause of carnitine-acylcarnitine translocase deficiency, which has relatively high frequency in Guangxi population, and is related to the founder effect.

This paper deeply studied the definition and characteristics of clinical research programs. On such basis, the researchers utilized theoretical and comparative studies in combination of practical studies, to probe deeply into both the operating procedures and management documents of the clinical research management council.These efforts contributed to constructing a systematic, overall and feasible management system,for reference of building such a council by medical institutions.

Rotavirus is one of the most common causes of gastroenteritis among children under five years of age worldwide. Most children are infected with rotavirus in their early childhood. Currently, no ef-fective treatment is available for diarrhea caused by rotavirus infection, and vaccination is the most effective way to prevent rotavirus infection. With the introduction of rotavirus vaccines, the morbidity and mortality of severe diarrhea in children caused by rotavirus infection are declined significantly, but these rotavirus vac-cines have significantly lower efficacy in developing countries in Africa and some countries in Asia where the mortality of rotavirus-related diseases is high than in developed countries. High titers of maternal antibodies may be one of the reasons why the efficacy of rotavirus vaccines is low in these countries. Extensive studies have been conducted on the relationship between neonatal response to rotavirus vaccine immunization and ro-tavirus-specific antibodies in the mother′s milk and serum in recent years. However, results of some studies are in conflict. In this review, we summarize the relationship between maternal antibodies and the immune responses after vaccination with rotavirus vaccines in order to provide basis for improving the efficacy of rota-virus vaccines in low-income countries.

Objective To use the matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) technique for detecting the mutation gene of neonatal non-syndromic hereditary hearing impairment gene in Guangxi and to investigate its effectiveness and feasibility in clinical application.Methods A total of 7 100 newborns were performed the hearing preliminary screening and secondary screening by adopting AABR.The genomic DNA was extracted by the heel blood spot.Twenty mutation characteristics of 4 deaf predisposing genes were detected by MALDI-TOF-MS.Results The pass rate of hearing screening in 7 100 newborns was 97.11％ (6 895/7 100),the positive rate of neonatal gene mutation was 3.54％ (251/7 100),in which the GJB2 gene mutation was in 131 cases,the carrying rate was 1.84％,235delC heterozygous mutation was in 108 cases.SLC26A4 gene mutation was in 93 cases,which dominated by 1229C＞T heterozygous mutation and IVS7-2A＞G heterozygous mutation,mtDNA12SRNA gene mutation was in 16 cases and GJB3 gene mutation was in 11 cases.Conclusion Adopting the MALDI-TOF-MS screening technique can increase the detection rate of hot point mutation in common deaf related genes and discover neonatal genetic NSHI from molecular level and provides the corresponding geneticconsulting guidance for early finding and predicting deaf occurrence,and formulating the interventional measures.

Objective To explore the situation of return-to-work (RTW) and its related factors in female injured works. Methods The da-ta of the basic information, counseling record and follow-up record after discharge were collected from social rehabilitation department in our center. The main influencing factors were analyzed by single factor analysis and two classification Logistic regression. Results 232 ob-jects were collected, among which, 149(64.2%) subjects had returned to work, and the median of absence time was 206.5 days. Single factor analysis indicated that their age, marriage, absence time and educational level were not correlated with the outcome of women injured work-ers' employment (P>0.05). However, place of social insurance, household register and injury severity correlated with the outcome (P<0.05). Conclusion Most of the female injured workers can return to work. The severity of injury, along with some system factors influence the RTW of them.