ObjectiveTo explore the effect of precocious puberty on glucose metabolism and lipid metabolism in female rats. MethodsSixty two-day-old female rats were randomly divided into 2 groups. When aged 5 days， the precocious puberty group and normal group were given a single subcutaneous injection of danazol and solvent soybean oil respectively. The vaginal opening of rats was monitored from their 21 days of age. After 12 hours of fasting， all successful modeling rats were randomly executed within 3 days after vaginal opening， when aged 7 and 12 weeks. Then we measured the rats’ body weight and length， determined the concentrations of glucose， insulin， blood lipids， estradiol， leptin and adiponectin with enzyme-linked immunosorbent assay and observed the pathological changes of perirenal fat， uterus and ovary. ResultsFor body weight and length， rats in the precocious puberty group were smaller than those in the normal group within 3 days after vaginal opening， but which did not affect their subsequent growth and development， and there was no significant difference between the two groups at 7 and 12 weeks of age. Within 3 days after vaginal opening， insulin levels had significant difference between the two groups （P = 0.001）， the precocious group showed hyperinsulinemia and increased number of perirenal adipocytes. At three execution times， no significant difference was noted in estradiol， leptin and adiponectin levels between the two groups. The same was true in the ratios of ovary or uterus to body weight between the two groups. ConclusionsPrecocious puberty makes earlier onset of pubertal development and allows body maladaptation to the sudden changes of the internal environment. However， the changes due to precocious puberty are temporary and reversible， and they may become normal in adulthood.

Wet age-related macular degeneration(wARMD)emerges as a primary contributor to irreversible vision impairment in the aging demographic. In clinical practice, anti-vascular endothelial growth factor(VEGF)therapies exhibit pronounced success in managing wARMD. However, in the actual clinical application, there are significant individual differences in the prognosis of anti-VEGF drug therapy, and some patients show poor response to the treatment, which may be related to the morphological differences of retinal layers in macular area, genetics, systemic conditions and other factors. It will help develop a more rational and individualized treatment plan to judge the prognosis of patients according to their different clinical manifestations in advance, so as to reduce overtreatment and the risk of retinal damage. In recent years, most studies on treatment response mainly focus on fundus morphology, genetics and so on. In this study, the relevant factors affecting adverse response to wARMD were reviewed, aiming to provide with more accurate treatment and prognostic monitoring programs for clinicians.

Objective To summarize and analyze the clinical phenotypes,hereditary features and treatment and follow-up strategies of different hereditary pheochromocytoma/paragangliomas(PCC/PGL)and related syndromes.Methods Forty-four clinically diagnosed PCC/PGL patients admitted in our hospital from January 2000 to August 2022 were enrolled,and the clinical data of them and their family members were collected.Second-generation sequencing was performed on 43 patients for genetic detection,and Sanger sequencing was applied to verify the mutation of the probands and family members.Results There were 15 patients diagnosed with hereditary PCC/PGL,including 7 cases of von Hippel-Lindau(VHL)syndrome,3 cases of multiple endocrine neoplasia type 2(MEN2),and 5 cases of familial paraganglioma syndrome.Seven VHL syndrome families were diagnosed as VHL2A(c.500G＞A),VHL2B(c.239G＞T and c.444_457del),and VHL2C(c.293A＞G)according to their clinical manifestations.All probands received surgical treatment,and 2 cases of recurrent PCC and the patients with multiple renal cancer also received targeted therapy with sunitinib.Three MEN2 families carried c.1901G＞C,c.1832G＞A,and c.1901G＞A missense mutations,respectively,and were diagnosed with MEN2A clinically.All of them underwent adrenalectomy and thyroidectomy,including one for preventive thyroidectomy.Among the 5 familial paraganglioma syndrome families,4 patients carried SDHB mutations(SDHB:c.343C＞T,c.541-2A＞G,c.575G＞A,c.268C＞T)and 1 patient carried an SDHD mutation(SDHD:c.337_340del).Sporadic retroperitoneal PGL were most common.Conclusion More than 1/3 of PCC/PGL patients carry germline gene mutations,showing obvious genotype-phenotype correlation.Genetic diagnosis technology plays an important guidance role for clinical precision treatment and follow-up,and genetic counseling.

Objective:To analyze pathogenic characteristics of viral diarrhea in children aged <5 years in Hebei Province and provide reference for the prevention and control of viral diarrhea in children.Methods:Stool samples were collected from in-patients with diarrhea under five years old from sentinel hospitals in Lulong County of Hebei between 2010 and 2020. ELISA detected rotavirus antigen, and then positive samples were genotyped by semi nested reverse transcription PCR of two rounds. Calicivirus, genotyping astrovirus, and adenovirus were detected by real-time fluorescence quantification PCR. The data were analyzed by using software SPSS 20.0.Results:In 2 925 detected stool samples, 1 919 (65.61%) were positive. The positive rates of rotavirus, calicivirus, adenovirus, and astrovirus were 42.80% (1 252/2 925), 22.12% (647/2 925), 6.19% (181/2 925), 3.56% (104/2 925). Viral diarrhea was mainly caused by rotavirus infection, accounting for 59.30% (1 017/1 715) between 2010 and 2017, and by calicivirus infection accounting for 53.43% (109/204) between 2018 and 2020. The peak positive rate of rotavirus occurred in winter, with the highest rate in infants aged 12 to 17 months (52.96%,483/912). In the rotavirus positive samples, G9P[8] was mainly detected strains (58.31%,730/1 252), followed by G3P[8] (8.15%,102/1 252). The calicivirus-positive samples were mainly infected with norovirus GⅡ. Sequence analysis indicated that the main type was GⅡ.4 [P31] between 2011 and 2016 and GⅡ.3 [P12] in 2018.Conclusions:Rotavirus and calicivirus were the main pathogens causing infant diarrhea in children under five years old in Hebei from 2010 to 2020. Winter was the main epidemic season.

Objective To observe the correlations of subchondral insufficiency fracture(SIF)of medial femoral condyle with medial meniscus injury pattern and medial meniscus extrusion(MME).Methods Data of 36 patients with clinically confirmed unilateral medial femoral condyle SIF were retrospectively analyzed.The patients were divided into low-grade and high-grade groups according to SIF grade.Cartilage injury,medial meniscus injury and MME were compared between groups,and the correlations of SIF grade with cartilage injury,osteonecrosis volume(OV)and MME were analyzed.Cartilage injury grade,OV and MME were compared between groups,and the correlations were explored.Results There were 18 cases in each group.The percentage of cartilage injury grade Ⅲ-Ⅳ,OV and MME value(the distance between the vertical line of medial meniscus and the vertical line of tibial plateau cartilage)in high-grade group were greater than those in low-grade group(all P＜0.05).Significant difference of injury grades of meniscus posterior horn was found between groups(P=0.007).SIF grade was positively correlated with cartilage injury grade,OV and MME value(rs=0.710,0.765,0.540,all P≤0.01).MME value was positively correlated with meniscal injury degree and tear range(rs=0.502,0.520,both P＜0.01).There were 4,19 and 13 cases with 0,1 and 2 grade MME,respectively,and significant differences of cartilage injury grades,OV and MME values were found among different MME grades(all P＜0.05).MME value was positively correlated with cartilage injury grade and OV(rs=0.451,0.579,both P＜0.01).Conclusion In SIF patients,OV and cartilage injury were both correlated with medial meniscus injury pattern and MME.

Objective:To investigate the construction effects of the graduate biochemistry technology courses based on the outcome-based education (OBE) concept, analyze the technical needs of graduate students, and further integrate and optimize the teaching methods.Methods:A self-compiled questionnaire with good reliability and validity was used to conduct an overall sampling survey on the graduate students who took the elective courses in Batch 2021 in a medical college in Shanghai. Excel and GraphPad Prism software were used for data analysis.Results:According to this survey, the courses gain good effects in terms of teaching framework, course facilities, teaching forms, teaching contents and comprehensive evaluation of teaching. A total of 112 students (95.2%) thought that the course was very helpful to the expansion of experimental technology and experimental operation ability. However, there were still some teaching needs, such as expanding the types of experiments and increasing experimental operations.Conclusions:Under the guidance of OBE concept, the construction of the graduate biochemistry technology courses has gradually achieved good results. Later, the online-offline hybrid teaching form will be further improved and the curriculum teaching arrangement will be optimized further.

Objective:To construct the clinical practice pathway for narrative medicine in traditional Chinese medicine(TCM),with a view to providing clinical practice guidelines for narrative medicine in TCM for frontline practitioners.Methods:Using the realistic literature review and the Nominal Group Technique(NGT),the paper systematically sorted out the practices of humanistic care in ancient Chinese medical books and famous medical cases,as well as constructed the first draft of the clinical practice pathway and details for narrative medicine in TCM.Subsequently,experts from multiple fields were invited to demonstrate by using the NGT.After in-depth discussion and collective voting,various operational modules,and their detailed rules and supporting tools were determined,thus completing the construction of the entire practical pathway.Results:A complete set of clinical practice pathways for narrative medicine in TCM had been established.It encompassed six core modules,including"start of diagnosis and treatment","communication of disease conditions","diagnosis and explanation","joint decision-making","end of diagnosis and treatment",and"reflection and summary".Besides,detailed operating rules and supporting tools were also provided.Conclusion:The clinical practice pathway for narrative medicine in TCM integrates the humanistic spirit of TCM,the core concepts of narrative medicine,and the communication skills of psychology,providing medical workers with standardized,procedural,and operationally flexible practice guidance,which helps both doctors and patients to better communicate,empathize,and make joint decisions throughout the entire process of diagnosis and treatment.

Objective:To analyze the association between the pre-pregnancy oral microbiota of women and fetal overgrowth, and the possible mechanisms involved.Methods:A nested case-control study design based on a pre-pregnancy cohort was used to select 51 mothers who delivered macrosomia and/or large-for-gestational-age (LGA) infants from the population recruited at the Maternal and Child Health Care Hospital of Jiading District in Shanghai from October 2016 to December 2021 as the case group. A control group was formed by selecting 204 mothers who delivered infants with normal birth weight and appropriate for gestational age during the same period, in a 1:4 ratio. The LGA subgroup consisted of 48 mothers who delivered LGA infants from the total population, and a corresponding control group of 192 was randomly selected from the remaining mothers who delivered non-LGA infants in a 1∶4 ratio for the LGA subgroup analysis. The 16S rRNA gene sequencing technique was utilized to detect pre-pregnancy saliva samples to compare the characteristics of the oral microbiota, differential microorganisms, and differential functional pathways between groups. Nonparametric Wilcoxon rank-sum tests, two independent samples t-tests, or Chi-square (or Fisher's exact) tests were used for statistical analysis. Factor analysis was conducted on the pre-pregnancy diet data of women, and the primary dietary pattern of each study subject was identified based on the highest score of the dietary pattern factors. For microbiota count data, α and β diversity indices were calculated using R and QIIME2 software, and the corresponding microbiota functional count data were acquired through PICRUSt2. Results:(1) General data: There was no significant difference in the time interval from pre-pregnancy sampling to pregnancy and from sampling to delivery between the two groups. In the case group, there were three cases of macrosomia and 48 cases (94.1%) of LGA. The corresponding control group for the LGA subgroup consisted of 192 cases. There were no significant differences in dietary patterns between the case group and the control group. (2) α diversity analysis: The species richness index of the case group was lower than that of the control group [(367.27±84.57) vs. (408.71±93.08), multivariate analysis, P=0.009], while no significant differences were found between the two groups in the Shannon and Simpson indices; the species richness index of the LGA subgroup was also lower than that of the corresponding control group [(371.04±83.92) vs. (408.04±94.21), multivariate analysis, P=0.033], with no significant differences in the Shannon and Simpson indices. (3) β diversity analysis: There was a statistically significant difference in the unweighted UniFrac distance of the oral microbiota between the case group and the control group ( R2=0.006, F=1.479, P=0.048). No significant differences were found in the β diversity indices of the oral microbiota between the LGA subgroup and the corresponding control group. (4) Differential microbiota analysis: There were 14 differential microbiotas from phylum to genus between the case group and the control group. At the genus level, members of the G1 genus of the Streptococcaceae were enriched in the case group, while the Lautropia, Dialister, Leptotrichia, and Rothia were enriched in the control group. In the LGA subgroup and its corresponding control group, there were 14 differential microbiota from phylum to genus; at the genus level, Leptotrichia, Rothia, G6 genus of the Saccharibacteria, and Selenomonas were enriched in the control group (all LDA value>2, and all P<0.05). (5) Differential functional analysis: In the case group, metabolic pathways such as nicotinate degradation [log 2 fold change ( FC)=3.510, q=0.005], de novo synthesis of pyrimidine nucleotides (log 2FC=0.078, q=0.005), and L-tyrosine degradation pathway (log 2FC=0.710, q=0.034) were enriched in the oral microbiota of women. In the LGA subgroup, compared to the corresponding control group, metabolic pathways related to nicotinate degradation were enriched in the oral microbiota (log 2FC=3.660, q=0.012). Conclusions:There are differences in the structure of the pre-pregnancy oral microbiota of mothers with overgrown fetuses compared to those with normally grown fetuses, and mothers of normally grown fetuses show higher diversity in their pre-pregnancy oral microbiota. The enrichment of certain pathogenic bacteria and the reduction of symbiotic bacteria in the pre-pregnancy oral microbiota are associated with fetal overgrowth, and this association may be mediated by functional pathways such as nicotinate degradation.

Objective:To summarize the clinical and genetic features of 7 patients with a mild form of Geleophysic dysplasia type 2(GD2)/Acromicric dysplasia(AD) induced by fibrillin 1(FBN1) gene mutation from one Chinese family.Methods:A Chinese pedigree of mild GD2/AD treated at the Pediatric Endocrinology Department at the First Affiliated Hospital of Sun Yat-sen University between August 2017 and May 2022 was collected. Whole-exome genetic sequencing of the FBN1 gene were performed to establish the diagnosis. Additionally, a literature review was further conducted.Results:In this family, among 13 individuals spanning three generations, there were 7 affected cases, including 1 adult female, 1 adult male, and 5 children. All individuals exhibited postnatal growth failure, severe disproportionate short stature, and lacked typical facial features. Exome sequencing and Sanger sequencing confirmed the presence of a heterozygous missense mutation c. 5099A>G(p.Tyr1700Cys) in exon 42 of the FBNI gene in 6 affected individuals(Ⅱ-1, Ⅲ-1 to Ⅲ-5), which was identified as a pathogenic mutation. This mutation was previously reported in a Chinese classical achondroplasia(AD) family. Based on comprehensive genetic analysis, clinical features, and multisystem evaluation, 3 cases were diagnosed with mild type 2 growth hormone deficiency(GD2), and 4 cases were diagnosed with mild AD. Recombinant human growth hormone(rhGH; 1.1-1.4 IU·kg -1·week -1) was applied to all the 5 children, and additional gonadotropin releasing hormone analogue(GnRHa) was administered to the 2 girls in late puberty, resulting in certain growth-promoting effect. Conclusions:The c. 5099A>G(p.Tyr1700Cys) mutation not only leads to the classical type of achondroplasia(AD) as reported in the literature but also causes the non-classical GD2 or AD(mild GD2/AD). Further research is warranted to investigate the long-term therapeutic effects of rhGH treatment.

【Objective】 To explore the characteristics of white matter degeneration in amyotrophic lateral sclerosis (ALS) patients with different onset and spreading patterns by using diffusion tensor imaging (DTI). 【Methods】 We enrolled 86 ALS patients and 44 healthy controls. The patients were divided into bulbar- and spinal-onset subgroups according to their onset site, as well as horizon, vertical, interpose/skip, and caudal-rostral subgroups based on the spreading direction of the involved regions. The white matter fiber tracts corresponding to the motor network were set as the region of interest. We used tract-based spatial statistics to evaluate differences between the above groups and the normal controls, with family-wise error (FWE) correction and P<0.05 as statistical significance. 【Results】 The white matter degeneration of ALS patients with bulbar onset was mainly limited to the corona radiation part of the corticospinal tract, while those with spinal onset showed extensive degeneration of corticospinal tract and corpus callosum Ⅲ area (FWE correction, P<0.05). In patients with horizontal and vertical dissemination, decreased integrity of the entire corticospinal tract was found, with patients in the latter group showed extra degeneration in the Ⅲ part of the corpus callosum. Restricted degeneration of the corticospinal tract within bilateral corona radiata was detected in patients with caudal-rostral and interposed/skip spreading pattens (FWE correction, P<0.05). 【Conclusion】 Different onset and disease spread patterns of ALS patients correspond to divergent brain degeneration patterns. The diagnosis, treatment, and management of ALS should fully consider the heterogeneity of the disease.