Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Currently, there are practical and technical difficulties in the construction of clinical questions in the development of clinical practice guidelines. Clinicians or guideline developers seldom construct clinical questions based the actual case scenario, leading to some information loss between structured and actual clinical connotation. To overcome this challenge, we proposed a case-guided questions construction approach, and carried out case research and verification in the formulation of the guideline. We found that this method could more efficiently and scientifically assist the formulation of clinical questions, and provide reference for clinicians or guideline developers.

Objective To explore the effect and mechanism of Baicalein in the treatment of hyperuricemia.Methods The mouse model of hyperuricemia was established by yeast extract combined with potassium oxazinate.The effect and potential mechanism of Baicalein in the treatment of hyperuricemia were studied by biochemical indexes,pathological changes,non-target metabonomics and network pharmacology.Results Baicalein could reduce the contents of serum uric acid,creatinine and blood urea nitrogen,reduce the inflammatory injury of renal tissue,up-regulate the expression level of uric acid excretion protein and down-regulate the expression level of uric acid reabsorption protein.Nine disease-related targets such as BCL2,SIRT1 and XDH were screened by network pharmacology.Six key metabolic pathways including nicotinic acid and nicotinamide metabolism,caffeine metabolism and purine metabolism were screened by metabonomics analysis.Conclusions Baicalein can treat hyperuricemia and reduce renal injury,and its mechanism may be related to the metabolic pathways of nicotinic acid and nicotinamide regulated by SIRT1 and quinolinate.

BACKGROUND: Hepatic fibrosis (HF) is a histopathological change in the process of long-term liver injury caused by cytokine secretion and internal environment disturbance, resulting in excessive liver repair and fiber scar. Nogo-B protein is widely distributed in peripheral tissues and organs and can regulate the migration of endothelial cells by activating TGFb1 in vascular remodeling after injury. Nogo-B has been shown to promote organ fibrosis. This study was to determine the role of Nogo-B in HF. METHODS: An HF model was built by intraperitoneal injections with 20% carbon tetrachloride. Localization of Nogo-B was detected by FISH. The interaction between Nogo-B and BACE1 was confirmed by Co-IP. Autophagy flux was analyzed using tandem mRFP-GFP-LC3 fluorescence microscopy, electron microscopy, and western blotting. Detection of serum AST and ALT and H&E staining were utilized to detect the degree of liver injury. The HF was evaluated by Masson trichromatic staining. RT-qPCR, western blotting, and immunofluorescence were employed to detect relevant indicators. RESULTS: Reducing Nogo-B suppressed AST and ALT levels, the accumulation of collagen I and a-SMA, and expressions of pro-fibrotic genes in mouse liver. BACE1 was a potential downstream target of Nogo-B. Nogo-B was upregulated in TGF-b1-activated hepatic stellate cells (HSCs). Knocking down Nogo-B caused the downregulation of profibrotic genes and inhibited viability of HSCs. Nogo-B knockdown prevented CCL4-induced fibrosis, accompanied by downregulation of extracellular matrix. Nogo-B inhibited HSC autophagy and increased lipid accumulation. BACE1 knockdown inhibited HSC autophagy and activation in LX-2 cells. CONCLUSION Nogo-B knockdown prevents HF by directly inhibiting BACe1-mediated autophagy.

The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the β-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10^-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10^-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.

ObjectiveTo determine the therapeutic effect of Gegentang granules on a disease-syndrome mouse model combining human coronavirus 229E （hCoV-229E） pneumonia with Hanshi Yidu Xifei syndrome in vivo. MethodMice were randomly divided into normal group， infection group， cold-dampness group， model group， chloroquine phosphate group （0.18 g·kg^-1）， interferon-α2b （IFN-α2b） group （1.83×10⁶ U·kg^-1）， Gegentang granules high-dose and low-dose groups （6.6， 3.3 g·kg^-1） with 10 mice in each group. Cold-dampness environment and hCoV-229E infection were used for modeling， and the general status and lung index of mice in each group were observed. The viral load in lung tissue was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， the pathological changes in lung tissue were evaluated by hematoxylin-eosin （HE） staining， the levels of serum gastrointestinal hormones and inflammatory factors in lung tissue were detected by enzyme-linked immunosorbent assay （ELISA）， and the percentage of peripheral blood lymphocytes was detected by flow cytometry. ResultComparing with model group， Gegentang granules could significantly alleviate the physical signs of Hanshi Yidu Xifei syndrome， including listlessness， weakness of limbs， sticky stool， etc. Comparing with model group， Gegentang granules high-dose group significantly reduced lung index， histopathological score of interstitial lung and bronchus， and the level of serum motilin （P<0.05， P<0.01）， two doses of Gegentang granules could significantly increase the level of serum gastrin （P<0.05， P<0.01）， the percentage of CD4⁺， CD8⁺ T lymphocytes in peripheral blood （P<0.05， P<0.01）， and the level of tumor necrosis factor-α （TNF-α） in lung tissue was significantly decreased （P<0.01）， and the level of interleukin-6 （IL-6） showed decreasing tendency. ConclusionGegentang granules has therapeutic effect on model mice. It can improve the appearance and behavior characterization， regulate the level of gastrointestinal hormones， decrease lung index and histopathological score， and possibly play an immunomodulatory role by inhibiting the expression of inflammatory cytokines in lung tissue and restoring the percentage of peripheral blood lymphocytes.

Objective:To explore the enhancement effect of different concentrations of contrast media on blood vessels and hollow organs in CT enterography.Methods:Sixty patients with CT enterography were enrolled from January to August 2019 at Shanghai Ninth People's Hospital, and were prospectively randomly divided into three groups (group A: 90 ml 400 mg/ml contrast media, group B: 90 ml 350 mg/ml contrast media, and group C: 79 ml 400 mg/ml contrast media). Evaluation parameters included CT value, signal noise ratio (SNR) and contrast noise ratio (CNR) of main abdominal vessels (abdominal aorta, superior and inferior mesenteric atery, jejunal artery, ileum artery, superior and inferior mesenteric vein), jejunum, ileum and inflammatory bowel disease. The overall image quality and direct jejunum ileum artery quality scores were evaluated. One-way ANOVA was used to compare the parameters among the three groups.Results:There was no statistical difference in CT value, SNR and CNR of each measurement index among the three groups in plain scan ( P>0.05). The CT value, SNR and CNR of abdominal aorta, superior mesenteric artery, inferior mesenteric artery, jejunal artery and ileal artery in group A and C were higher than those in group B in arterial phase ( P<0.05), but there was no significant difference between group A and group C ( P>0.05). The CT value, SNR and CNR of superior mesenteric vein, inferior mesenteric vein, normal jejunum, ileum and inflammatory lesions in group A were higher than those in group B and C in venous phase ( P<0.05), but there was no significant difference between group B and group C ( P>0.05). The overall image quality scores of group A, B and C were (3.8±0.7), (3.4±0.6), (3.4±0.6), respectively, with no significant difference ( F=3.075, P=0.054). The direct jejunum ileum artery scores of the three groups were (3.5±0.5), (3.1±0.5), (3.4±0.5), respectively, the difference was statistically significant ( F=3.684, P=0.031). Conclusion:At the same injection rate and scanning parameters, contrast media at 400 mg/ml can provide better vessel and hollow organ enhancement.

In this study,the SH-SY5Y cell model with Parkinson"s disease-like lesions was established by using rotenone,and the effect and mechanism of fibroblast growth factor 21 (FGF21) on the cell model were explored. Different concentrations of FGF21 were used to treat neuronal injury model induced by rotenone,and cell viabilities were detected by MTT assay. Effects of FGF21 and rotenone on the apoptotic levels of SH-SY5Y cells were analyzed by using Annexin V-FITC detection kit. Western blot was used to assess the effects of FGF21 and rotenone on the protein levels of tyrosine hydroxylase (TH) and α-synuclein (α-syn) in SH-SY5Y cells. Effects of FGF21 and rotenone on reactive oxygen species (ROS) levels in SH-SY5Y cells were tested using DCFH-DA fluorescent probe. The results showed that FGF21 could reduce the damage in SH-SY5Y cells induced by rotenone,inhibit cell apoptosis,alleviate the abnormalities of TH and α-syn in SH-SY5Y cells induced by rotenone and down-regulate the abnormal ROS levels in SH-SY5Y cells. The results suggested that FGF21 may attenuate rotenone-induced neuronal damage through regulation of oxidative stress.

Objective: To investigate the clinical, imaging and molecular characteristics of primary hyperoxaluria type 1 (PH1) in children and to sum up existing evidence for further understanding the phenotype-genotype correlation of infantile PH1. Methods: This retrospective analysis was based on the medical records of children with PH1 diagnosed by gene test in the Department of Nephrology, Guangzhou Women and Children′s Medical Center from June 2016 to May 2019. Targeted exome sequencing was performed on tubular disease-related genes of the probands and Sanger sequencing was conducted to validate suspected pathogenic variants of family members. Logistic regression analysis of NC and CCr was adopted to show the relation between NC and renal function. The literature review was conducted, and the clinical, imaging and molecular biogenetic characteristics of the disease were analyzed and summarized. Results: A total of 7 children from 6 families were enrolled. The median age of onset was 5 months. The median age of diagnosis was 8 months. Five cases had progressed to end-stage renal disease (ESRD), one case had chronic kidney disease (CKD) stage 1, and the other one had CKD stage 2. Four cases died, one case maintained on hemodialysis, and the other two non-dialysis cases were followed up. Among the 7 cases, 4 patients had infantile PH1, 1 patient had child and adolescent type, 1 patient had family type and the other one had unknown classification. There were two siblings (the younger brother had uremia and the sister had normal renal function) who had the delayed diagnosis for 5 and 3 years respectively. All patients in this cohort had proteinuria and microscopic hematuria, but no patients had gross hematuria. Three cases had hypercalciuria. Comprehensive diagnostic imaging evaluation include CT scan, MR scan, radiography and ultrasound led to the diagnosis of nephrocalcinosis (NC) in 5 cases, including 4 cases of simple NL and 1 case of NC with nephrolithiasis (NL), 1 case of multiple NL and 1 case of microcrystal deposition in renal medulla. However, only one case of NC was identified by ultrasound, the other 4 cases of NC were identified by radiograph examination. In the logistic regression analysis involving NC and creatinine clearnce rate (CCr), the results showed that NC was an independent risk factor for renal dysfunction (OR 2.5, 95%CI 0.7-1.2, P<0.05). All the 7 cases had AGXT gene variant, including homozygous variant in 4 cases and compound heterozygous variant in 3 cases. A total of 9 variant genotypes were found, and exon 6 variants were found in 4 children. Among them, there were 3 cases with c.679_680delAA. To our knowledge, both c.679_680delAA and c.190A>T in the cohort have not been reported previously. Conclusions Infantile PH1 is the most common type of PH1 in children, which progresses rapidly or even begins with renal failure, with poor prognosis. It is also highly heterogeneous in phenotype and genotype. NC is an independent risk factor leading to renal failure. Radiograph examination showed high specificity for the diagnosis of NC. At present, the misdiagnosis and delayed diagnosis of PH1 are still common in China. It is of great significance to carry out quantitative determination of uric oxalate in order to reduce the misdiagnosis rate and enhance follow-up technologies for evaluating the therapeutic effect.