OBJECTIVES: To study genotype-phenotype correlations in children with FGFR3 variants and to improve clinical recognition of related disorders. METHODS: Clinical data of 95 patients aged 0-18 years harboring FGFR3 variants, confirmed by whole‑exome sequencing at Shanghai Children's Medical Center from January 2012 to December 2023, were retrospectively reviewed. Detailed phenotypic characterization was performed for 22 patients with achondroplasia (ACH) and 10 with hypochondroplasia (HCH). RESULTS: Among the 95 patients, 52 (55%) had ACH, 24 (25%) had HCH, 9 (9%) had thanatophoric dysplasia, 3 (3%) had syndromic skeletal dysplasia, 2 (2%) had severe achondroplasia with developmental delay and acanthosis nigricans, and 5 (5%) remained unclassified. A previously unreported FGFR3 variant, c.1663G>T, was identified. All 22 ACH patients presented with disproportionate short stature accompanied by limb dysplasia, commonly with macrocephaly, a depressed nasal bridge, bowed legs, and frontal bossing; complications were present in 17 (77%). The 10 HCH patients predominantly exhibited disproportionate short stature with limb dysplasia and depressed nasal bridge. CONCLUSIONS ACH is the most frequent phenotype associated with FGFR3 variants, and missense variants constitute the predominant variant type. The degree of FGFR3 activation appears to correlate with the clinical severity of skeletal dysplasia.
Humans ; Receptor, Fibroblast Growth Factor, Type 3/genetics* ; Child ; Male ; Child, Preschool ; Female ; Infant ; Adolescent ; Dwarfism/genetics* ; Achondroplasia/genetics* ; Lordosis/genetics* ; Infant, Newborn ; Retrospective Studies ; Genetic Association Studies ; Bone and Bones/abnormalities* ; Phenotype ; Limb Deformities, Congenital

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective:To explore the application value of contrast-enhanced ultrasound (CEUS) combined with transvaginal ultrasound features and quantitative parameters in evaluating high-risk endometrial cancer (EC).Methods:Retrospective analysis was made on 69 EC patients who received CEUS examination and were confirmed by surgery and pathology in Beijing Shijitan Hospital, Capital Medical University from December 2017 to September 2022. According to postoperative pathology, the patients were divided into low-risk group ( n=38) and high-risk group ( n=31). The differences in CEUS, transvaginal ultrasound features and quantitative parameters between the two groups were compared, relevant parameters that with predictive value for high-risk EC were screened, and these parameters were scored. Results:①There were differences in lesion size (thick diameter, long diameter), vascular morphology, and color blood flow score between high and low risk ECs (all P<0.05). ②There were differences in CEUS parameters [perfusion mode, enhancement intensity, area under curve(AUC)] between high and low risk EC groups (all P<0.05). ③The areas under the ROC curve for diagnosing high-risk EC were 0.79, 0.69, 0.69, and 0.62, respectively, based on the critical values of lesion thickness diameter ≥1.85 cm, lesion length diameter ≥2.05 cm, ultrasound contrast quantification parameter AUC ≥859 au, and enhancement intensity ≥29.4 dB. ④Using statistically significant parameters for scoring, the sensitivity and specificity for diagnosing high-risk EC with the score ≥5, were 70.97% and 89.47%, respectively. Conclusions:The combination of CEUS and transvaginal ultrasound is a feasible method for predicting high-risk EC. CEUS parameters (enhanced intensity, AUC, and " focal" perfusion mode) are related to high-risk EC. The combination of CEUS and transvaginal ultrasound helps to pre-evaluate the pathological prognostic factors of endometrial malignant lesions before surgery, providing a basis for clinical follow-up treatment.

Objective: To establish the reference standard of the median nerve conduction study (NCS) in Korea. Methods: A total of 648 median motor and 602 median sensory NCSs from 349 Korean healthy volunteers were tested and analyzed prospectively. Equipment calibration, assessment of intraand inter-rater reliability, and the NCSs per se were conducted according to a predetermined protocol. A reference standard was established from uncertainty components for the following parameters: the onset and peak latencies; the baseline-to-peak and peak-to-peak amplitudes; the area and duration of the negative wave; and the nerve conduction velocity. The effects of sex, age and stimulation intensity were analyzed. Results: Each measured value of 648 median motor and 602 median sensory nerves were obtained and presented with both mean and expanded uncertainties, as well as mean and standard deviations. The cut-off values with expanded uncertainty were determined for different age and sex groups. After adjusting for anthropometric covariates, all parameters except duration were affected by age, and sex appeared to influence both duration and area. While stimulation intensity significantly affected some parameters including latencies, the effect sizes were negligible. Conclusion We propose the median NCS reference standard using the largest Korean dataset ever available. The use of the traceable and reliable reference standard is anticipated to promote more accurate and dependable diagnosis and appropriate management of median neuropathies in Korea.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Aim To verify the role of Shengjiang Powder in sepsis and explore its molecular mechanism. Methods The targets of drug active ingredients and disease-related targets were searched by TCMSP, Disgenet and other databases, and the intersection of the two was selected. DAVID database was used to carry out enrichment analysis of GO and KEGG pathways for intersection targets, and molecular docking was performed between drug active ingredients and core genes of key pathways. Mouse model of sepsis was constructed by cecal ligation puncture (CLP). Spleen tissue and serum of mice were collected. The percentage of T cell subsets in spleen was detected by flow cytometry, and IL-6 and IL-10 levels in serum were detected by ELISA. Results A total of 25 active ingredients, 238 targets of active ingredients, 2797 disease-related targets, 90 genes of intersection between active ingredients and disease-related targets, potential targets were AKT, JUN, EGFR, MMP9, etc. GO enrichment analysis showed 1021 items, including 942 biological processes, 23 cell compositions and 55 molecular functions. KEGG pathway analysis found that the intersection genes were mainly enriched in THE PD-1/PD-L1 signaling pathway, HIF-1 signaling pathway, TNF signaling pathway and inflammatory mediators signaling pathway, indicating that the therapeutic effect may be related to these pathways. The molecular docking results showed that quercetin, kamanol, emodin and other core compounds could be well combined with key genes. Flow cytometry results showed that after seven days of CLP, the proportion of CD4 T cells in spleen decreased, the proportion of CD4 PD-1 T cells increased, the release of IL-6 decreased, the content of IL-10 increased, and the mice were immunosuppressed. The percentage of CD4 T cells in spleen increased, the number of CD4 PD-1 T cells decreased, the release of IL-6 was enhanced, the content of IL-10 decreased, and the immunosuppression was improved. Conclusions It is proved that Shengjiang Powder can increase the release of pro-inflammatory cytokine IL-6, increase the ratio of CD4 T/CD8 T cells, and decrease the expression of anti-inflammatory cytokine IL-10 in the late stage of sepsis, so as to improve immune suppression in the late stage of sepsis and improve the survival rate of mice.

Osteochondral lesion of talus (OLT) is a foot and ankle disease characterized by ankle pain, which may impact the joint function and life quality. If managed improperly, it may lead to a further ankle arthritis, severely compromising the prognosis. The therapeutic effect of conservative treatment for OLT is still uncertain. Surgery is still the main treatment modality for OLT with various techniques. However, the optimized surgical technique is still inconclusive, furthermore, regeneration and repair of cartilage after debridement is also a great challenge for the treatment of OLT. Platelet-rich plasma (PRP) with good repair effect on cartilage injury is gradually applied in the treatment of OLT. However, there still lacks the unified understanding of the technique and specification of PRP for the treatment of OLT. Therefore, National Orthopedics Center of Shanghai Sixth People′s Hospital allied Foot Ankle Basic Research & Orthopedics Group, Chinese Association of Orthopedic Surgeons; Foot and Ankle Committee of Chinese Association of Sports Medicine Physicians; and Foot and Ankle Group of Orthopedic Specialized Branch of Shanghai Medical Association to organize related experts to formulate the Expert consensus on platelet- rich plasma treatment for osteochondral lesion of talus ( version2023). Fifteen recommendations were put forward upon PRP preparation, indications, contraindications and treatment methods of PRP for OLT, so as to standardize the PRP treatment for OLT.

The study aims to explore the effects and mechanisms of water extract of Potentilla anserina (PA) on myelosuppression mice induced by cyclophosphamide based on metabonomics. The myelosuppressive mouse model was established by injected with cyclophosphamide and treated with water extract of PA. Thymus and spleen indexes, peripheral hemogram and bone marrow nucleated cells of each group was detected. Bone marrow pathology analysis was performed by hematoxylin-eosin staining. The levels of interleukin 3 (IL-3), interleukin 6 (IL-6), erythropoietin (EPO), granulocyte colony stimulating factor (GM-CSF), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in serum were measured. The changes of biomarkers and related metabolic pathways were analyzed by UPLC-Q-TOF/MS-based metabonomics. Animal experiments were approved by the Animal Ethics Committee of Southwest Minzu University. The high doses of PA could significantly improve the decrease of white blood cell (WBC), red blood cell (RBC) counts and hemoglobin (HGB) levels of mice induced by cyclophosphamide (P < 0.05), and significantly increase the number of nucleated cells and the area of hematopoietic tissue in femoral bone marrow. The medium and high doses of PA could significantly improve the serum levels of SOD, CAT, MDA, IL-6 and GM-CSF (P < 0.05), and have no significant effect on the expression of IL-3 and EPO (P > 0.05). Serum metabolomics analysis showed that the aqueous extracts of PA could alleviate myrosuppression by regulating the aminoacyl-tRNA, valine, leucine and isoleucine biosynthesis mediated by 13 different metabolites such as valine, leucine, asparagine and hydroxyisohexic acid. PA improve the inhibition of hematopoietic function in myelosuppression mouse, and its mechanisms may be related to anti-oxidation and promoting the expression of hematopoietic-related cytokines and regulating the related metabolic pathways.

Anesthesia, General/adverse effects* ; Hypertension/etiology* ; Humans