Using Liquid Chromatography-Tandem Mass Spectrometry in Detecting Plasma Lyso-GL3 Levels in Patients with Fabry Disease and the Association Analysis of Phenotype-Genotype of the Disease / 罕见病研究

ObjectiveUsing the liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine the plasma level of Lyso-GL3 in patients with Fabry disease and to analyze the clinical application of the method.MethodsThirty-nine patients with a genetic diagnosis of Fabry disease were included, and plasma levels of Lyso-GL3 were measured by LC-MS/MS analysis, and detailed clinical information of the patients was obtained including: α-galactosidase A activity, genetic variants, quantification of urine protein, mean arterial pressure, and estimation of glomerular filtration rate, and the differences in the levels of Lyso-GL3 in different clinical phenotypes and genotypes were statistically analyzed, as well as the association with clinical indicators.ResultsLyso-GL3 showed good linearity within 0.7856-400 ng/mL(r=0.9992).Further analysis of 39 Fabry disease patients diagnosed in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine showed a median Lyso-GL3 concentration of 23.6 ng/mL(4.3-92.9 ng/mL); Lyso-GL3 levels were significantly higher in patients with both the frameshift and the splicing mutations, as well as in patients with the nonsense mutations, than in patients with the missense mutations (median value 119.7 ng/mL vs. 11.9 ng/mL, P=0.006, and median value 97.0 ng/mL vs. 11.9 ng/mL, P=0.015, respectively). Whereas, association analysis revealed that Lyso-GL3 was not significantly associated with urinary protein, mean arterial pressure and estimated glomerular filtration rate.ConclusionsThe using of LC-MS/MS to quantify plasma Lyso-GL showed significant differences in Lyso-GL3 concentrations between classical and atypical phenotypes, suggesting that plasma Lyso-GL3 may help with clinical phenotypes. However, Lyso-GL3 levels is found to be overlapped between genotypes. No significant linear correlation was found between Lyso-GL3 and renal clinical indicators, suggesting the urgent need in finding a more accurate tool to assess renal involvement and prognosis in patients with Fabry disease.

Considerations on the improvement of height benefit in children with central precocious puberty / 中国当代儿科杂志

With the changes in various factors such as genetics and the environment, the incidence of childhood precocious puberty has been gradually increasing. Improving height is one of the key issues in the clinical management of precocious puberty. Currently, gonadotropin-releasing hormone analogs (GnRHa) remain the preferred treatment for precocious puberty, but their effect on height improvement is influenced by multiple factors, which may result in lower-than-expected height benefits. Combining recombinant human growth hormone (rhGH) therapy with GnRHa treatment is an alternative strategy to enhance the efficacy of GnRHa, but there is still no clear recommendation regarding the timing of their combination. Considering the current status of precocious puberty treatment, it is crucial to reevaluate the effects of GnRHa monotherapy and combination therapy with rhGH on height improvement. This article discusses strategies such as combination therapy indications to guide clinical medication and help children with precocious puberty achieve optimal height benefits.

No Incidence of Liver Cancer Was Observed in A Retrospective Study of Patients with Aristolochic Acid Nephropathy / 中国结合医学杂志

OBJECTIVE@#To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN).@*METHODS@#A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014.@*RESULTS@#A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer.@*CONCLUSIONS@#No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.

Analysis of the Results of Deafness Gene Screening in 301 Severe and Very Severe Non-syndrome Deafness Children / 医学研究杂志

Objective To study the results of the deafness gene in 301 children with severe and very severe non-syndrome deafness in Xinjiang,to provide a reference for rehabilitation and genetic counseling after cochlear implantation.Methods A total of 301 patients with severe and very severe non-syndrome deafness who were admitted to the People's Hospital of Xinjiang Uygur Autonomous Region from 2017 to 2019 were collected.After informed consent,the patients were screened for deafness genes,including 25 loci in GJB2,SLC26A4,mt12SrRNA,OTOF,and SLC17A8 genes(c.35delG,c.167delT,c.176_191del16,c.235delC,c.299_300delAT,c.281C＞T,c.589G＞A,c.IVS7-2A＞G,c.1174A＞T,c.1226G＞A,c.1229C＞T,c.IVS15+5G＞A,c.1975G＞C,c.2027T＞A,c.2162C＞T,c.2168A＞G,c.1494C＞T,c.1555A＞G,c.1585A＞G,c.1047A＞G,c.1095T＞C,c.960_961 insC/961delT,c.4023G＞A,c.4819C＞T,c.824C＞A),and the detection results were analyzed.Results Among 301 cases of severe and very severe non-syndrome deaf-ness,80 cases of positive mutation were screened,and the total detection rate was 26.58％(80/301).The mutation rates of GJB2,SLC26A4,and mt12SrRNA genes were 10.96％(37/301),12.62％(38/301),and 4.32％(13/301),respectively.The main forms of GJB2 mutations were c.235delC and c.35delG,accounting for 37.50％(30/80)and 8.75％(7/80)of the mutations,respectively.The main forms of SLC26A4 mutations were c.IVS7-2A and c.1174 A＞T,accounting for 26.25％(21/80)and 11.25％(9/80)of the mutations,respectively.The main mutation forms of mt12SrRNA were c.960_961 insC/961delT and c.1555A＞G,accounting for 7.50％(6/80)and 5.00％(4/80)of the mutations,respectively.The c.4023G＞A and c.4819C＞T mutations in OTOF and c.824C＞A mutations in SLC17A8 were not detected.The total detection rate of mutation sites in the Han nationality was significantly higher than that in the Uygur nationality(x2=19.064,P＜0.001).Conclusion GJB2 and SLC26A4 are common pathogenic genes in children with severe and very severe non-syndrome deafness in Xinjiang.There may be other hot spot mutation sites in the Uygur nationality.

Effects of Bushen formulae on bone metabolism and ENaCα,NCC and ClC-3 expression in ovariectomized rats with high salt intake / 中国病理生理杂志

AIM:To investigate the effect of Bushen formulae(BHF)on bone metabolism and its possible mechanism in ovariectomized rats with high salt intake.METHODS:According to the random number table method,80 SPF-grade Sprague-Dawley rats were divided into sham group,ovariectomy(OVX)group,medium-high-salt diet(MSD)group,high-salt diet(HSD)group,BHF group,BHF with normal saline(BHF+NS)group,BHF+MSD group,and BHF+ HSD group,with 10 rats in each group.After modeling,different diets and BHF formula interventions were administered,and the concentrations of sodium chloride added to MSD group and HSD group were 2%(w/w)and 8%(w/w),respective-ly.The dose of BHF was 7.8 g·kg-1·d-1,once a day,and the treatment lasted for 12 weeks.Bone density,bone microar-chitecture,bone parameters,bone metabolism biomarkers,bone histopathological changes,the expression of epithelial sodium channel α(ENaCα),Na-Cl cotransporter(NCC),and voltage-gated chloride channel 3(ClC-3)proteins in bone tissue were detected in each group.RESULTS:Compared with sham group,the rats in OVX group had reduced bone density and destroyed bone microstructure.Compared with OVX group,the bone microstructure in MSD and HSD groups was more significantly damaged,while the levels of bone formation markers,bone glycoprotein(BGP)and type Ⅰ procolla-gen N-terminal peptide(PINP),were significantly increased in HSD group(P<0.05).Moreover,the levels of bone re-sorption markers,such as amino-terminal cross-linked telopeptides of type Ⅰ collagen(NTX),carboxy-terminal cross-linked telopeptides of type Ⅰ collagen(CTX)and tartrate-resistant acid phosphatase(TRACP),were significantly in-creased(P<0.05),indicating that bone metabolism was in high-conversion state.High-salt diet accelerated the structural destruction of bone trabeculae,and Western blot results showed that high-salt diet caused decreases in the protein expres-sion levels of ENaCα and ClC-3 and an increase in the protein expression level of NCC in femoral tissues(P<0.05).After BHF intervention,the expression of relevant ion channels caused by high salt could be regulated to different degrees.CONCLUSION:Bushen formulae could differentially regulate the expression of relevant ion channels ENaCα,ClC-3,and NCC induced by high salt to different degrees,which has certain ameliorative and therapeutic effects on the imbalance of bone metabolism.

Research on selection and subsidy standards of extended essential public health services program in China / 中国卫生政策研究

Objective:To meet people's increasing needs for essential public health services in different regions of China,and to adjust the needs of essential public health services according to local conditions,including demographic characteristics,disease burden,economic development level,etc.Methods:The selection and evaluation framework of extended essential public health services was developed through a literature review,based on the Multi-criteria decision analysis theory,and the operational selection process and subsidy standard of extended essential public health services were explored through conducting case simulation for public health intervention programs.Results:The study initially constructed a selection and evaluation framework containing three dimensions and eight indicators,and formed the process and steps for selecting and adjusting the provincial essential public health services programs.Conclusions:The study provides an evidence-based reference for the governments'decision-making on adjusting the connotation of the local essential public health services system.

Consistent analysis of swept-source optical coherence tomography and time-domain optical coherence tomography in measuring the parameters of chamber angle of patients with myopia / 中国医学装备

Objective:To investigate the consistency of swept-source optical coherence tomography(SS-OCT)and time-domain optical coherence tomography(TD-OCT)in measuring the parameters of anterior chamber angle.Methods:A total of 46 myopic patients(92 eyes)were retrospectively selected from Department of Ophthalmology of Army Specialty Medical Center from January 2023 to May 2023.Both SS-OCT and TD-OCT were used to measure respectively the parameters of anterior chamber angle of patients.And then,the differences of central anterior chamber depth(ACD),angle opening distance(AOD500,AOD750),scleral spur angle(SSA),trabecular iris area(TISA500,TISA750)between SS-OCT and TD-OCT were compared and analyzed.The Pearson correlation analysis and Bland-Altman test were adopted to analyze and measure the correlation and consistency of the measures.Results:There was significant difference in ACD between the two kinds of scan methods(t=-6.83,P<0.001).Additionally,the differences of the AOD500,AOD750,SSA500,TISA500 and TISA750 of measured data beside of nose were significant(t=-5.16,5.51,-6.51,-4.75,-5.69,P<0.001),respectively.Similarly,the differences of them beside of temple were significant(t=-5.04,-4.8,-6.06,-3.84,-4.02,P<0.001),respectively.There was positive correlation between the two kinds of scan methods(r=0.71-0.92).The Bland-Altman analysis showed that 2.1% to 8.9% of the measured values were outside the consistency limit by 95%.Conclusion:There are differences between SS-OCT and TD-OCT in the measures of the parameters of anterior chamber angle of myopic patients,and the measured results of them appear positive correlation.

Research progress on influencing factors and training of nurses'compassion / 中华护理杂志

Compassion is an important part of nurses'professional quality,and it is also the basis of effective nurse-patient communication and humanistic care.Improving nurses'compassion is helpful to provide high-quality nursing services to patients.This study reviews the definition of compassion,the factors affecting compassion and the training methods to improve compassion,analyzes the shortcomings of existing training methods,and puts forward the prospects for future research,so as to provide a theoretical foundation for future compassion training among nurses.

Diagnosis and treatment of rosacea in the real world: a survey on the current status / 中华皮肤科杂志

Objective:To analyze the current status of diagnosis and treatment of rosacea in China, and to strengthen the understanding and management of this disease.Methods:A retrospective cross-sectional study was conducted, and patients with rosacea were enrolled from 23 tertiary hospitals in 6 provinces or municipalities in northern and southern China. Clinical characteristics, previous diagnosis and treatment status of these patients were collected through questionnaires. Non-normally distributed continuous data were described by M ( Q1, Q3), and compared using Mann-Whitney U test, while categorical data were compared using chi-square test. Results:Among the 593 patients with rosacea, 164 were males and 429 were females, with a male-to-female ratio of 1∶2.6; 205 patients were from southern China, and 388 from northern China; most patients (349 cases, 58.8%) were aged 20 to 40 years, and the patients from northern China were significantly older than those from southern China (median age: 37 years vs. 30 years, P < 0.001). Multiple-site involvement (371 cases, 62.6%) and coexistence of multiple phenotypes (391 cases, 65.9%) were common, the cheeks (429 cases, 72.3%) and nose (393 cases, 66.3%) were mostly affected, and skin lesions mainly manifested as persistent erythema (354 cases, 59.7%), papulopustules (344 cases, 58.0%), and telangiectasia (282 cases, 47.6%). Involvement of the cheeks was more common in the patients from southern China (160 cases, 78.0%) than in those from northern China (269 cases, 69.3%), but the nose and eyes were less involved in the patients from southern China than in those from northern China (nose: 125 cases [61.0%] vs. 268 cases [69.1%]; eyes: 3 cases [1.5%] vs. 23 cases [5.9%]; both P < 0.05). The prevalence of transient erythema and papulopustules was significantly higher in the patients from southern China (38.0% and 65.4%, respectively) than in those from northern China (20.9% and 54.1% respectively, both P < 0.05), while the patients from northern China more frequently presented with persistent erythema compared with those from southern China (64.9% vs. 49.8%, P < 0.05). The disease duration ( M [ Q1, Q3]) was 12 (4, 30) months among the patients with rosacea, and the time from the onset to diagnosis was 10 (3, 24) months. The disease duration was significantly longer (12 [4, 36] months), and the proportion of patients with disease duration > 5 years was significantly higher (16.4% [63 cases]) in the patients from northern China than in those from southern China (12 [3, 24] months, 9.4% [19 cases], respectively; both P < 0.05). The patients with varied subtypes and severity of rosacea were previously mainly treated with topical antimicrobial agents (71.9%) ; 72.7% of the patients with mild rosacea were treated with systemic drugs; poor patient compliance was observed, and only 40.6% of the patients completed more than 4 consecutive weeks of treatment at a time. Conclusions:Rosacea usually occurred in young and middle-aged people in China, mostly involved the cheeks and nose, and mainly manifested as erythema or papulopustules. Delayed diagnosis, non-standard treatment and poor patient compliance existed in clinical practice.

Clinical and genetic analysis of children with developmental and epileptic encephalopathy 18 caused by SZT2 gene variants / 中华神经科杂志

Objective:To investigate the clinical phenotype and genetic characteristics of developmental epileptic encephalopathy 18 (DEE18) caused by SZT2 gene variants. Methods:Clinical data of 2 children with SZT2 related DEE18 who visited the Department of Pediatric Neurology, Linyi People′s Hospital in March 2020 and July 2023 were collected. The whole exome sequencing (WES) and Sanger sequencing were applied to verify the child and their parents. SWISS-MODEL software was used to perform protein 3D modeling for the selected SZT2 gene variants. Results:Both of the 2 cases showed severe global developmental delay, epileptic seizures, autism, megacephaly, facial deformity, hypotonia, corpus callosum malformation, persistent cavum septum pellucidum, and slow background activity and focal discharge in video electroencephalography. Case 1 was easy to startle and thin in stature; case 2 had immune deficiency and clustered seizures. WES results showed that case 1 carried a compound heterozygous variant of c.5811G>A (p.W1937X) (paternal) and c.9269delG (p.S3090Ifs *94) (maternal), while case 2 carried a compound heterozygous variant of c.6302A>C(p.H2101P) (paternal) and c.7584dupA (p.E2529Rfs *20) (maternal), the parents of both patients with normal clinical phenotypes. The 4 mutations mentioned above were novel variations that had not yet been reported domestically or internationally. According to the American College of Medical Genetics and Genomics variant classification criteria and guidelines, the p.S3090Ifs *94 variant was interpreted as pathogenic; p.W1937X variant was interpreted as pathogenic; p.E2529Rfs *20 variant was interpreted as likely pathogenic; p.H2101P variant was interpreted as uncertain significance. 3D modeling showed that the variant of p.H2101P resulted in a significant change in the hydrogen bond around the 2 101st amino acid encoded, leading to a decrease in protein stability. The other 3 variants led to early truncation of peptide chain and obvious changes in protein structure. Conclusions:DEE18 caused by SZT2 gene mutation is mainly an autosome recessive genetic disease, and its clinical manifestations include global developmental delay, epileptic seizures, autism, craniofacial malformation, hypotonia, epileptic discharge, corpus callosum malformation, persistent cavum septum pellucidum, shock, small and thin stature, and immune deficiency. Four novel variants related to the SZT2 gene may be the genetic etiology of DEE18 patients in this study.

Clinical phenotype and genetic analysis of BRWD3 gene variation related infantile epileptic spasm syndrome / 中华神经科杂志

Objective:To investigate the clinical phenotype and genetic characteristics of infantile epileptic spasm syndrome caused by BRWD3 gene mutation. Methods:Clinical data of a child with BRWD3 related infantile epileptic spasm syndrome who was admitted to Department of Pediatric Neurology of Linyi People′s Hospital on August 2, 2019 were collected and followed up, whole exome sequencing technology and Sanger sequencing were applied to verify the child and his parents, and the pathogenicity of mutation site was analyzed. The studies till June 2023 were searched with keywords of " BRWD3" in both English and Chinese databases of China National Knowledge Infrastructure, Wanfang, Online Mendelian Inheritance in Man, and PubMed. The clinical phenotype and genetic characteristics of patients with BRWD3 related epilepsy were summarized. Results:The patient was a 4 years and 4 months old boy, with a clinical phenotype including severe global development delay, focal seizures (the onset age was 4 months), epileptic spasm (the onset age was 6 months), autism, megacephaly, high forehead as well as hypsarrhythmia. The whole exome sequencing results showed a de novo and frameshift variation c.4318_4319del(p.Q1441Efs*20)(NM_153252) in the BRWD3 gene, and the variation was interpreted as pathogenic (PVS1+PS2+PM2) according to the American College of Medical Genetics and Genomics variant classification criteria and guidelines. A total of 7 English literature articles were retrieved reporting 16 cases of BRWD3 gene related epilepsy in children (including 1 case of infantile epileptic spasm syndrome), and there has been no report in China yet. Totally there were 17 cases of BRWD3 gene related epilepsy including this case. All the cases showed X chromosome dominant inheritance, of whom 15 cases showed minor variations, including 7 missense variations, 3 frameshift variations, 3 splicing variations, 2 nonsense variations, and the remaining 2 cases showed large segment deletions. A total of 15 different variants were found. The phenotypes of the 17 patients mainly included epileptic seizures (17/17), intellectual disability (10/17), motor development disorder (7/17), speech impairment (9/17), megacephaly (8/17), facial malformation (8/17), autism (4/17) and hypotonia (4/17). The common seizure types were found to be focal seizures, occasionally epileptic spasm seizures and tonic seizures. Conclusions:BRWD3 gene variation related epilepsy is an X chromosome dominant genetic disease with a wide clinical phenotype spectrum. BRWD3 gene mutation c.4318_4319del(p.Q1441Efs *20) could cause infantile epileptic spasm syndrome, manifested as severe global developmental delay, epileptic spasm, focal seizures, autism, craniofacial malformation and hypsarrhythmia. This research enriches BRWD3 gene mutation spectrum.

Clinical phenotype and genotype characteristics of tuberous sclerosis complex in 52 children / 中华神经科杂志

Objective:To analyze the clinical phenotypes and TSC1/TSC2 gene variations in 52 children with tuberous sclerosis complex. Methods:The clinical data of 59 children with tuberous sclerosis complex hospitalized in Linyi People′s Hospital between January 2017 and October 2022 were collected. The analysis of TSC1 and TSC2 gene variations on main family members was performed, and then bioinformatics analysis followed. The positive children were divided into TSC1 gene group and TSC2 gene group, and the difference of clinical characteristics between the two groups was analyzed. Results:Among 59 children, 52 cases were detected TSC1/ TSC2 gene variations (17 cases in the TSC1 gene group and 35 cases in the TSC2 gene group). Of the 52 children, 28 (53.8%) were male, 24 were female (46.2%); 17 (32.7%) were familial cases (10 with TSC1 gene variations and 7 with TSC2 gene variations), 35 (67.3%) were sporadic cases; 46 (88.5%) had hypomelanotic macules, 13 (25.0%) had facial angiofibromas, 5 (9.6%) had shagreen patches, 49 (94.2%) had subependymal nodules/calcifications, 47 (90.4%) had cortical nodules, 2 (3.8%) had subependymal giant cell astrocytomas, 39 (75.0%) had intellectual/developmental disabilities, 49 (94.2%) had epileptic seizures, 8 (15.4%) had cardiac rhabdomyomas, 9 (17.3%) had renal angiomyolipomas, and 4 (7.7%) had retinal hamartomas. Of the 52 children, 49 variations were detected, including 4 large fragment deletion/duplication variations, and 45 point variations; 41 pathogenic variations, 7 likely pathogenic variations, and 1 variation of uncertain significance. In this study, 16 point mutations and 1 large fragment duplication mutation which had not been reported at home and abroad, and 3 high-frequency mutation sites (p.Arg692 *, p.Arg228 *, and p.Arg1200Try) were found. There was a statistically significant difference in the proportion of familial cases [10/17 vs 7/35(20%), χ2=7.838, P=0.005], median onset age of epilepsy [38.0(0.5-134.0) months vs 8.0(0.1-63.0) months, Z=3.506 , P<0.001] and the incidence of developmental retardation/intellectual impairment [8/17 vs 31/35(88.6%), χadj2=8.423, P=0.004] between the TSC1 gene and TSC2 gene groups. Conclusions:Tuberous sclerosis compiex has widespread phenotypes, can affect every body system, especially the skin and nervous system. The pathogenic gene is TSC1/ TSC2. The TSC1 gene group has more familial cases. The TSC2 gene group has an earlier onset age of epilepsy and a higher incidence of developmental retardation/intellectual impairment. In this study, 16 novel point mutations, 1 novel large fragment duplication mutation, and 3 hotspot mutations were identified, expanding the gene variation spectrum of tuberous sclerosis complex.

Efficacy and safety of botulinum toxin type A in improving face and neck aging / 中华医学美学美容杂志

Objective:To evaluate the clinical effectiveness and safety of combined face and neck injections of botulinum toxin type A to improve face and neck aging.Methods:From January 2020 to January 2023, 30 female patients with age of 29-66 years, average (42.2±8.8) years, underwent face and neck combined injection of A-type botulinum toxin in the Department of Dermatology, Henan Provincial People′s Hospital. The injection sites included the forehead, between the eyebrows, around the eyes, the dorsum of the nose, and the mandibular margin, etc. The efficacy was assessed by the wrinkle severity scale (FWS) and the AB value of the distance from the lowest point of the mandibular margin on the midline of the hemiface to the level of the medial canthus at 4 and 24 weeks after the injection, as well as the subjective degree of improvement by the Global Aesthetic Improvement of the Face Scale (GAIS) and the Self-perception of Age (SPA), and the satisfaction of the patients and post-injection adverse reactions.Results:At 4 weeks after the injection, the total effective rate of improvement of wrinkles in all parts of the upper face was 100% (30/30), and there was a statistically significant difference in the improvement of AB ( t=28.35, P<0.05). At 24 weeks after the injection, the total effective rate of improvement of wrinkles in all parts of the upper face ranged from 16.7% (5/30) to 36.7% (11/30), and the improvement of AB still showed a statistically significant difference ( t=3.98, P<0.05). 100% (30/30) and 66.7% (20/30) of patients assessed their facial status as improved on GAIS at 4 and 24 weeks after the injection, respectively, and 100% (30/30) and 63.3% (19/30) of patients perceived themselves as younger. Patient satisfaction was 100% (30/30). After injection, there were 5 cases of slight ecchymosis at the injection site and 1 case of weakness in eyebrow elevation in the 30 patients, which disappeared on their own within 1 to 2 weeks. Conclusions:The therapeutic effect of face and neck combined injection of botulinum toxin type A on facial rejuvenation is obvious, with high patient′s satisfaction and no serious adverse reactions.

Effects of different fortified feeding methods on the nutrient metabolism and growth rate of very low birth weight preterm infants / 中国儿童保健杂志

【Objective】 To analyze the effects of different fortified feeding methods on nutritional metabolism and growth rate of preterm very low birth weight infants (VLBWI), in order to provide new clues for improving the prognosis of the preterm infants. 【Methods】 A total of 115 cases of premature VLBWI admitted to Department of Neonatology, The First Affiliated Hospital of Kunming Medical University from January 2019 to December 2020 were included in this study, and were divided into fortified breastfeeding group (HFM group), mixed feeding group, and premature formula feeding group (PF group) based on their feeding methods. The effects of different feeding methods on the nutritional metabolism and growth rate of premature VLBWI were analyzed. 【Results】 1) The hospitalization time of infants in the HFM group was shorter than that in PF group and mixed feeding group (t=7.185, 6.924, P<0.05). 2) The proportion of necrotizing enterocolitis (NEC) in the HFM group during hospitalization was lower than that in the PF group (P<0.05); the proportions of late onset septicemia(LOS) and extra uterine growth restriction(EUGR) in the HFM group during hospitalization were lower than those in the PF group (χ2=5.030, 4.147, P<0.05); the proportion of LOS was lower than that of the mixed feeding group(χ2=6.589, P<0.05). 3) During hospitalization, the proportions of abdominal distension, bloody stools and increased eosinophils in the HFM group were lower than those in the PF group (P<0.05), which in mixed feeding group was lower than those in PF group (Fisher exact test, P<0.05). 4) At discharge, the weight and length growth rate of the HFM group were higher than those of the mixed feeding group (t=3.722, 0.425, P<0.001) and the PF group (t =6.015, 0.496, P< 0.001). 【Conclusion】 Fortified breastfeeding can more effectively increase the growth rate of VLBWI in premature infants, improve nutritional metabolism, reduce complications and adverse feeding reactions related to premature infants, and is safer and more effective.

Using Liquid Chromatography-Tandem Mass Spectrometry in Detecting Plasma Lyso-GL3 Levels in Patients with Fabry Disease and the Association Analysis of Phenotype-Genotype of the Disease / 罕见病研究

ObjectiveUsing the liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine the plasma level of Lyso-GL3 in patients with Fabry disease and to analyze the clinical application of the method.MethodsThirty-nine patients with a genetic diagnosis of Fabry disease were included, and plasma levels of Lyso-GL3 were measured by LC-MS/MS analysis, and detailed clinical information of the patients was obtained including: α-galactosidase A activity, genetic variants, quantification of urine protein, mean arterial pressure, and estimation of glomerular filtration rate, and the differences in the levels of Lyso-GL3 in different clinical phenotypes and genotypes were statistically analyzed, as well as the association with clinical indicators.ResultsLyso-GL3 showed good linearity within 0.7856-400 ng/mL(r=0.9992).Further analysis of 39 Fabry disease patients diagnosed in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine showed a median Lyso-GL3 concentration of 23.6 ng/mL(4.3-92.9 ng/mL); Lyso-GL3 levels were significantly higher in patients with both the frameshift and the splicing mutations, as well as in patients with the nonsense mutations, than in patients with the missense mutations (median value 119.7 ng/mL vs. 11.9 ng/mL, P=0.006, and median value 97.0 ng/mL vs. 11.9 ng/mL, P=0.015, respectively). Whereas, association analysis revealed that Lyso-GL3 was not significantly associated with urinary protein, mean arterial pressure and estimated glomerular filtration rate.ConclusionsThe using of LC-MS/MS to quantify plasma Lyso-GL showed significant differences in Lyso-GL3 concentrations between classical and atypical phenotypes, suggesting that plasma Lyso-GL3 may help with clinical phenotypes. However, Lyso-GL3 levels is found to be overlapped between genotypes. No significant linear correlation was found between Lyso-GL3 and renal clinical indicators, suggesting the urgent need in finding a more accurate tool to assess renal involvement and prognosis in patients with Fabry disease.

Influence of preoperative HbA1c level on posterior membrane opacity after phacoemulsification in diabetic patients and analysis of threshold effect / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To analyze the predictive value and threshold effect of preoperative glycated hemoglobin(HbA1c)level on posterior capsular opacification(PCO)in diabetic cataract patients.METHODS:Retrospective study. A total of 106 diabetic patients(106 eyes)with cataract treated in our hospital from September 2018 to September 2020 were collected. The patients were divided into PCO group(52 cases, 52 eyes)and non-PCO group(54 cases, 54 eyes)according to whether PCO occurred at 36 mo after surgery. The risk factors affecting postoperative PCO were analyzed. The threshold effect of HbA1c level on the occurrence of postoperative PCO was analyzed. The predictive value of preoperative HbA1c level in postoperative PCO was evaluated using the receiver operating characteristic(ROC)curve. The prediction model was constructed, and Bootstrap resampling was used to verify the prediction model, and the differentiation and accuracy of the model were evaluated.RESULTS: There were significant differences in diabetes course, diabetic retinopathy, fasting blood glucose, 2 h postprandial blood glucose, preoperative HbA1c, axial length and nuclear grade between PCO and non-PCO groups(P&#x003C;0.05). Duration of diabetes ≥12 a, presence of DR, fasting blood glucose ≥8 mmol/L, 2 h postprandial blood glucose ≥12 mmol/L, preoperative HbA1c ≥7%, axial length ≥30 mm, and nuclear grade Ⅲ or above were all influencing factors for postoperative PCO(P&#x003C;0.05). Curve fitting found that the probability of postoperative PCO showed an increasing trend with the increase of HbA1c level. Threshold effect analysis found that the incidence of postoperative PCO increased with the increase of HbA1c level when HbA1c≥7%. Sensitivity analysis showed that E value=2.129. The analysis of the correlation effect between preoperative HbA1c and the degree of PCO after phacoemulsification showed that the adjusted preoperative HbA1c level was an independent factor affecting the degree of PCO in diabetic patients(OR=1.65, 95% CI: 1.42-1.76, P=0.021). PCO outcome in diabetic cataract patients was indicated when the predictive model P=0.6, and the prediction accuracy of the model was 88.51%. Sensitivity and specificity were 86.33% and 86.82%, respectively.CONCLUSION:Duration of diabetes, presence of DR, fasting blood glucose, 2 h postprandial blood glucose, preoperative HbA1c, axial length, and nuclear grade were independent risk factors for postoperative PCO in diabetic patients, and preoperative HbA1c could be used as a sensitive index to evaluate postoperative PCO.

Mechanism of Modified Tianwang Buxindan on Skin of Sleep-deprived Mice Through PI3K/Akt/Nrf2 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of modified Tianwang Buxindan （MTBD） on the skin of sleep-deprived （SD） mice and investigate its mechanism. MethodSixty 2-month-old female Kunming mice were randomly divided into a blank group， a model group， a vitamin C （VC， 0.08 g·kg-1）， and MTBD low-， medium-， and high-dose groups （6.5， 12.5， 25 g·kg-1）. Except for the blank group， the other groups were subjected to SD mouse model induction （using multiple platform water environment method for 18 hours of sleep deprivation daily from 15：00 to next day 9：00）， continuously for 14 days， and caffeine （CAF， 7.5 mg·kg-1） was injected intraperitoneally from the 2nd week onwards， continuously for 7 days. While modeling， the blank group and the model group were administered with normal saline （0.01 mL·g-1）， and the other groups received corresponding drugs for treatment. On the day of the experiment， general observations were recorded （such as body weight， spirit， fur， and skin）. After sampling， skin tissue pathological changes were observed under an optical microscope using hematoxylin-eosin （HE） and Masson staining methods. Skin thickness and skin moisture content were measured. Biochemical assay kits were used to detect skin hydroxyproline （HYP） content， skin and serum superoxide dismutase （SOD） activity， and malondialdehyde （MDA） content. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum interleukin （IL）-6， tumor necrosis factor （TNF）-α， and IL-1β levels in mice. Western blot was used to detect skin tissue type Ⅰ collagen （ColⅠ）， type Ⅲ collagen （ColⅢ）， phosphatidylinositol 3-kinase （PI3K）， phosphorylated （p）-PI3K， protein kinase B （Akt）， p-Akt， nuclear factor E2-related factor 2 （Nrf2）， heme oxygenase （HO）-1， and nuclear factor （NF）-κB protein expression. ResultCompared with the blank group， the model group showed varying degrees of changes. In general， signs of aging such as reduced body weight （P<0.01）， listlessness， dull fur color， and formation of wrinkles on the skin appeared. Tissue specimen testing revealed skin thinning， flattening of the dermoepidermal junction （DEJ）， and reduced collagen fibers under the optical microscope. Skin thickness and moisture content decreased， skin tissue HYP content significantly decreased （P<0.01）， skin and serum SOD activity significantly decreased （P<0.01）， and MDA content significantly increased （P<0.01）. Serum IL-6， TNF-α， and IL-1β levels significantly increased （P<0.01）. Skin ColⅠ， ColⅢ， p-PI3K/PI3K， p-Akt/Akt， Nrf2， and HO-1 protein expression significantly decreased （P<0.05， P<0.01）， and NF-κB expression increased （P<0.01）. Compared with the model group， the VC group and the MTBD low-dose group showed increased skin moisture content， HYP content， SOD activity， and ColⅠ， ColⅢ， p-PI3K/PI3K protein expression （P<0.05， P<0.01）， and decreased serum MDA content （P<0.05）. In addition， a decrease in serum IL-6 and IL-1β levels was detected in the MTBD low-dose group （P<0.05）， while the above indicators in the MTBD medium- and high-dose groups improved （P<0.05， P<0.01）. ConclusionSleep deprivation accelerates the aging process of the skin in SD model mice. MTBD can improve this phenomenon， exerting anti-inflammatory and antioxidant effects， and its mechanism of action may be related to the activation of the PI3K/Akt/Nrf2 signaling pathway.

Scutellarin inhibitting BV-2 microglia-mediated neuroinflammation via the cyclic GMP-AMP synthase-stimulator of interferon gene pathway / 解剖学报

Objective To explore the effect of scutellarin on lipopolysaccharide(LPS)induced neuroinflammation in BV-2 microglia cells.Methods BV-2 microglia were cultured and randomly divided into 6 groups:control group(Ctrl),cyclic GMP-AMP synthetase(cGAS)inhibitor RU320521 group(RU.521 group),LPS group,LPS+RU.521 group,LPS+scutellarin pretreatment group(LPS+S)and LPS+S+RU.521 group.The expressions of cGAS,stimulator of interferon gene(STING),nuclear factor kappa B(NF-κB),phosphorylated NF-κB(p-NF-κB),neuroinflammatory factors PYD domains-containing protein 3(NLRP3)and tumor necrosis factor α(TNF-α)in BV-2 microglia were detected by Western blotting and immunofluorescent double staining(n= 3).Results Western blotting and immunofluorescent double staining showed that compared with the control group,the expression of cGAS,STING,p-NF-κB,NLRP3 and TNF-α in BV-2 microglia increased significantly after LPS induction(P<0.05),while the expression of cGAS,STING,p-NF-κB,NLRP3 and TNF-α in LPS+S group were significantly lower than those in LPS group(P<0.05).Treatment with cGAS pathway inhibitor RU.521 showed similar effects as the pre-treatment group with scutellarin.In addition,the change of NF-κB in each group was not statistically significant(P>0.05).Conclusion Scutellarin inhibits the neuroinflammation mediated by BV-2 microglia cells,which may be related to cGAS-STING signaling pathway.

Genome wide association study on genetic risk factors of deep vein thrombosis after trauma / 临床检验杂志

Objective To investigate the genetic risk factors of deep vein thrombosis(DVT)after trauma.Methods In a nested case-control study,50 patients with DVT after traumatic lower extremity fractures and 50 patients without DVT were recruited.The two groups were matched with gender,age and fracture sites.Preoperative venography was performed to diagnose DVT in trauma patients.Genome wide association study(GWAS)was used to investigate the genetic risk factors for preoperative DVT after traumatic lower ex-tremity fractures.Genomic DNA in leukocytes from blood sample was extracted and used for GWAS.Results GWAS was conducted based on 2 662 single nucleotide variants(SNV)which were dispersed in 144 interested genes.Ten genes were found to have signifi-cant association with trauma-related DVT,including cofactors of hemostasis mechanism,i.e.,THBD,F5,SERPIND1 and ITGA2,the factors related to vitamin K-dependent(VKD)carboxylation,i.e.,GGCX and CALU,and the members of cytochrome P450 family,i.e.,CYP1A1,CYP3A4,CYP2C19 and CYP2B6.Conclusion DVT after trauma might be regulated by the cofactors of hemostasis mechanism,the factors related to VKD carboxylation and the members of cytochrome P450 family.The results of our study may provide reference and inspiration for genetic susceptibility of preoperative DVT after trauma.

The effects of cannabidiol on the expression of NLRP3 inflammasome following multiple cerebral concussions in rats / 神经解剖学杂志

Objective:To investigate the effects of cannabidiol(CBD)on the NOD-like receptor protein 3(NLRP3)inflammasome in the brains of rats with multiple cerebral concussions(MCC).Methods:Rats were subjec-ted to the MCC model and divided into Sham,MCC,vehicle(MCC+TW),CBD-L(10 mg/kg),and CBD-H(40 mg/kg)groups.Immunofluorescence double staining was used to observe changes in NLRP3 and microglial cells in the brain,and Western Blot was performed to detect the expression changes of the NLRP3 inflammasome.Results:A sig-nificant increase in lectin-positive microglial cells of the cortex with enlarged cell bodies and elevated immunofluores-cence intensity of NLRP3 in the activated microglial cells was revealed by immunofluorescence double staining following MCC(P＜0.05).The immunofluorescence intensity of NLRP3 in the activated microglial cells was downregulated by the administration of CBD,with a more pronounced effect observed in the CBD-H group compared to the CBD-L group(P＜0.05).The expression of NLRP3,caspase-1,and apoptosis-associated speck-like protein(ASC)in the cortex,hippocampus,and basal ganglia of rats following MCC was significantly increased,as shown by Western Blot analysis(P＜0.05),and cortical areas are more elevated.The expression of these proteins in different brain regions was reduced by CBD-10 and CBD-40 intervention(P＜0.05).Conclusion:Cannabidiol can reduce the inflammatory response of multiple cerebral concussions rats through NLRP3 inflammasome and protect nerve tissue.