Objective This study aimed to identify PAX9 variants in non-syndromic tooth agenesis families of Chi-na,as well as to analyze the genotype-phenotype of non-syndromic tooth agenesis caused by PAX9 variants,which can provide a basis for the genetic diagnosis of tooth agenesis.Methods We collected the data of 44 patients with non-syn-dromic oligodontia who underwent treatment at Stomatological Hospital of Hebei Medical University between 2018 and 2023.Whole-exome sequencing was performed on the peripheral blood of the proband and its core family members,and the variants were verified by Sanger sequencing.Pathogenicity analysis and function prediction of the variants were per-formed using bioinformatics tools.The correlation between the genotype of PAX9 variant and its corresponding pheno-type was examined by reviewing 55 publications retrieved from PubMed.The studies involved 232 tooth agenesis pa-tients with PAX9 variants.Results A novel PAX9 c.447delG(p.Pro150Argfs*62)and a reported PAX9 c.406C>T(p.Gln136*)were identified in two Chinese families.Through bioinformatics analysis and three-dimensional structural mod-eling,we postulated that the frameshift variant was pathogenic.The outcome was the premature cessation of PAX9 pro-tein,which caused severe structural and functional deficiencies.Summarizing the PAX9 genotype-phenotype relationship revealed that patients carrying the PAX9 variant commonly led to loss of the second molars.Conclusion We identified the novel PAX9 c.447delG(p.Pro150Argfs*62)in a Chinese family of non-syndromic oligodontia,expanding the known variant spectrum of PAX9.The most susceptible tooth position for PAX9 variants of tooth agenesis was the second mo-lars and the deciduous molars during the deciduous dentition.

Objective:To automatically segment diabetic retinal exudation features from deep learning color fundus images.Methods:An applied study. The method of this study is based on the U-shaped network model of the Indian Diabetic Retinopathy Image Dataset (IDRID) dataset, introduces deep residual convolution into the encoding and decoding stages, which can effectively extract seepage depth features, solve overfitting and feature interference problems, and improve the model's feature expression ability and lightweight performance. In addition, by introducing an improved context extraction module, the model can capture a wider range of feature information, enhance the perception ability of retinal lesions, and perform excellently in capturing small details and blurred edges. Finally, the introduction of convolutional triple attention mechanism allows the model to automatically learn feature weights, focus on important features, and extract useful information from multiple scales. Accuracy, recall, Dice coefficient, accuracy and sensitivity were used to evaluate the ability of the model to detect and segment the automatic retinal exudation features of diabetic patients in color fundus images.Results:After applying this method, the accuracy, recall, dice coefficient, accuracy and sensitivity of the improved model on the IDRID dataset reached 81.56%, 99.54%, 69.32%, 65.36% and 78.33%, respectively. Compared with the original model, the accuracy and Dice index of the improved model are increased by 2.35%, 3.35% respectively.Conclusion:The segmentation method based on U-shaped network can automatically detect and segment the retinal exudation features of fundus images of diabetic patients, which is of great significance for assisting doctors to diagnose diseases more accurately.

OBJECTIVE To establish comprehensive quality evaluation method based on multi-index components combined with multivariate statistical analysis， and to comprehensively evaluate the quality of Periploca forrestii. METHODS Taking 11 batches of P. forrestii medicinal materials from different areas in Guizhou as samples， the contents of neochlorogenic acid， cryptochlorogenic acid， chlorogenic acid， procyanidin A2， isochlorogenic acid A and isochlorogenic acid C were determined by HPLC. Clustering heat map analysis， grey correlation analysis（GRA） and technique for order preference by similarity to ideal solution（TOPSIS） were used to evaluate the quality of P. forrestii. RESULTS The results of methodological investigation of content determination were in accordance with the relevant regulations， and the linear relationship and accuracy of each component were good in their respective sampling range. The contents of chlorogenic acid， cryptochlorogenic acid， neochlorogenic acid， procyanidin A2， isochlorogenic acid A and isochlorogenic acid C in 11 batches of samples were 3.650-7.302， 0.888-2.575， 1.371- 2.386， 0.947-1.469， 0.084-0.169 and 0.725-1.067 mg/g， respectively. The content of each component was significantly different， with the highest content of chlorogenic acid and the lowest content of isochlorogenic acid A. The comprehensive results of cluster heat map， GRA and TOPSIS analysis showed that the comprehensive quality of S5 and S10 was relatively good. CONCLUSIONS The established method is accurate， stable and simple. Combined with multivariate statistical analysis method， it can be used for quality evaluation of P. forrestii. The quality of samples from Jiuzhou Town and Caiguan Town of Xixiu District in Anshun City of Guizhou Province are relatively good among 11 different origin samples.

Objective To investigate the therapeutic effect of traditional Chinese medicine (TCM) on portal vein thrombosis (PVT) in patients with liver cirrhosis and its medication characteristics. Methods A retrospective analysis was performed for 89 patients with liver cirrhosis and PVT who were hospitalized and treated in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, and according to whether TCM treatment was applied in combination, they were divided into TCM group with 59 patients and control group with 30 patients. Related data were collected for the two groups, including demographic data, laboratory examination, radiological examination, gastroscopy, history of surgery, portal hypertension-related complications, medication, and follow-up data. The independent samples t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. An ordinal polytomous Logistic regression analysis was used for multivariate analysis. TCM Inheritance Computing Platform (V3.0) was used to perform a drug effect cluster analysis of TCM prescriptions. Results The multivariate logistic regression analysis showed that esophageal and gastric varices (odds ratio [ OR ]=3.144, 95% confidence interval [ CI ]: 1.221-8.094), PVT involving the portal vein (PV) and the superior mesenteric vein (SMV) ( OR =51.667, 95% CI : 3.536-754.859), PVT involving PV+spleen vein (SV)+SMV ( OR =13.271, 95% CI : 2.290-76.928), cavernous transformation of the portal vein ( OR =11.896, 95% CI : 1.172-120.696), and TCM intervention ( OR =0.348, 95% CI : 0.129-0.938) were influencing factors for the outcome of PVT in liver cirrhosis. Follow-up results showed that compared with the control group, the TCM group had a significantly lower progression rate (16.95% vs 56.67%, P < 0.001) and a significantly lower incidence rate of variceal rupture and bleeding (8.47% vs 33.33%, P < 0.001). Effective TCM drugs with a relatively high frequency of use included deficiency-tonifying drugs (359 times, 34.6%), blood-activating and stasis-resolving drugs (202 times, 19.5%), and diuresis-inducing and dampness-draining drugs (180 times, 17.3%); the TCM drugs with a relatively high frequency of use included Astragalus membranaceus (57 times, 8.7%), Angelica sinensis (50 times, 7.6%), and leech (48 times, 7.3%); TCM drug combinations with a relatively high frequency of use included Astragalus membranaceus+Angelica sinensis, Astragalus membranaceus+leech, Angelica sinensis+leech, and Astragalus membranaceus+Angelica sinensis+leech. Conclusion Qi-tonifying, blood-activating, and stasis-breaking drugs, such as Astragalus membranaceus, Angelica sinensis, and leech, can promote the stabilization or recanalization of PVT in liver cirrhosis and reduce the incidence rate of bleeding events due to portal hypertension.

OBJECTIVE To provide reference for quality control of Gentiana rhodantha. METHODS Taking 52 batches of G. rhodantha as subject， ultra-high performance liquid chromatography （UPLC） fingerprint was adopted. The similarity of 52 batches of medicinal materials samples was evaluated by the Similarity Evaluation System for Chromatographic Fingerprints of Traditional Chinese Medicine （2004A edition）； the content of mangiferin was determined； chemometric analyses [cluster analysis， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA）] were performed. RESULTS UPLC fingerprints of 52 batches of G. rhodantha were established， 17 common peaks were identified， and 6 of them were identified， which were loganic acid （peak 1）， neomangiferin （peak 3）， swertiamarin （peak 5）， dangyin （peak 6）， mangiferin （peak 7） and isoorientin （peak 9）. The similarities of 52 batches of medicinal materials samples were all greater than 0.9； cluster analysis showed that S1-S46， S48-S52 clustered into one class， and S47 alone； PCA results showed that the cumulative variance contribution rate of the first six principal components was 82.928%； OPLS-DA results showed that the corresponding components of swertiamarin， mangiferin and chemical composition represented by peak 4， 14， 15， 16 were the main iconic components affecting the quality differences of G. rhodantha medicinal materials. The contents of mangiferin in 52 batches of medicinal material samples ranged from 18.2 to 101.0 mg/g， mostly in accordance with 2020 edition of Chinese Pharmacopoeia. CONCLUSIONS The established UPLC fingerprint and chemometric analysis methods combined with content determination method of mangiferin can comprehensively evaluate the quality of G. rhodantha.

OBJECTIVE To prepare celastrol -loaded albumin nanoparticles （CLT-AN），and to investigate their activity against rheumatoid arthritis （RA）in vivo . METHODS CLT-AN was prepared by ultrasonic method . The formulation technology was optimized by single -factor test by taking particle size ，polydispersity index （PDI）and stability as indexes ，with the dosage of CLT ， the dosage of soybean oil and the ultrasonic power as factors . The physical and chemical properties of CLT -AN were investigated by transmission electron microscopy （TEM）and laser particle size analyzer ；in vitro stability and release profile were studied . A rat model of adjuvant -induced arthritis was constructed to investigate the effects of CLT -AN on joint swelling ，the levels of serum inflammatory factors [tumor necrosis factor α（TNF-α）and interleukin -1β（IL-1β）] and pathological state of joint tissue . RESULTS The optimized formulation was CLT 6.5 g，soybean oil 45 mg，ultrasonic power 490 W，ultrasonic time 8 min. CLT- AN prepared by the best formulation showed uniform and spherical morphology . Its particle size ，PDI，Zeta potential were （96.8± 1.1）nm，0.174±0.020，and（－18.6±1.7）mV，respectively. The encapsulation efficiency and drug -loading efficiency were （94.61±0.46）% and（2.42±0.21）%. There were no significant changes in particle size ，PDI，Zeta potential and encapsulation efficiency of CLT -AN within 5 days of storage at room temperature . CLT-AN was slowly released in vitro ，and the cumulative release reached 73.56% in 72 h. Compared with CLT ，CLT-AN could significantly inhibit the joint swelling of model rats ，reduced the levels of inflammatory factors TNF -α and IL -1β in serum ，and improved the pathological state of inflammatory joint tissue . CONCLUSIONS CLT-AN prepared by ultrasonic method has the appropriate particle size ，good stability ，significant sustained - release characteristics ，and excellent therapeutic efficacy against RA .

Liver cirrhosis is a major global health burden worldwide due to its high risk of morbidity and mortality. Role of terlipressin for the management of liver cirrhosis-related complications has been recognized during recent years. This paper aims to develop evidence-based clinical practice guidance on the use of terlipressin for liver cirrhosis-related complications. Hepatobiliary Study Group of Chinese Society of Gastroenterology and Hepatology Committee of Chinese Research Hospital Association invited gastroenterologists, hepatologists, infectious disease specialists, surgeons, and clinical pharmacists to formulate the clinical practice guidance based on comprehensive literature review and experts' clinical experiences. Overall, 10 major statements regarding efficacy and safety of terlipressin in liver cirrhosis - related complications were proposed. Terlipressin can be beneficial for the management of cirrhotic patients with acute gastroesophageal variceal bleeding and hepatorenal syndrome (HRS). However, the evidence regarding the use of terlipressin in cirrhotic patients with ascites, post-paracentesis circulatory dysfunction and bacterial infections, as well as in those undergoing hepatic resection and liver transplantation remains insufficient. Terlipressin - related adverse events, mainly including gastrointestinal symptoms, electrolyte disturbance, and cardiovascular and respiratory adverse events, should be closely monitored. The current clinical practice guidance supports the use of terlipressin for gastroesophageal variceal bleeding and HRS in liver cirrhosis. High-quality studies are needed to further clarify its potential effects in other liver cirrhosis-related complications.

The composition of serum is extremely complex,which complicates the discovery of new pharmaco-dynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich low-abundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and devel-oped a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56％using PC-based proteomic analysis,which was twice the number of proteins iden-tified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.

Objective:To learn about the status of iodine deficiency disorders (IDD) and iodine nutrition of residents in Shanxi Province since the implementation of the standard of "Iodine Content in Edible Salt" (GB 26878-2011), to evaluate the level of prevention and control of IDD, and to provide scientific basis for adjusting prevention and control strategies.Methods:The data of core indicators monitored by Shanxi Province in accordance with the requirements of the national iodized salt and IDD monitoring program for each year from 2012 to 2021 were comprehensively reviewed, and the change trends of the indicators such as coverage rate of iodized salt, consumption rate of qualified iodized salt, children's median urinary iodine and goiter rate, and pregnant women's median urinary iodine were analyzed; the evaluation of IDD elimination in counties (cities and districts, hereinafter referred to as counties) was analyzed.Results:From 2012 to 2021, the coverage rate of iodized salt in Shanxi Province was remained > 95%; from 2012 to 2014 (transition period between new and old standard iodized salt), the consumption rate of qualified iodized salt had an upward trend (χ 2trend = 2 703.32, P < 0.001), with a downward trend from 2015 to 2017 (before and after the reform of the salt industry system, χ 2trend = 122.18, P < 0.001), and with an upward trend from 2018 to 2021 (after the reform of the salt industry system, χ 2trend = 455.11, P < 0.001), from 2018, the consumption rate of qualified iodized salt remained > 90%; from 2015 to 2021, the average content of salt iodine was between 23 - 25 mg/kg, and the coefficient of variation of salt iodine was 15% - 18%. From 2014 to 2021, the median urinary iodine of children in Shanxi Province remained at 200 - 250 μg/L, the median urinary iodine of pregnant women remained at 150 - 200 μg/L, and the goiter rate of children remained below 5%. Every year, iodine nutrition of pregnant women in some counties was insufficient. In 2016, the proportion of counties with insufficient iodine nutrition of pregnant women was high, reached 30.0% (12/40); from 2018 to 2021, the proportion of counties with insufficient iodine nutrition of pregnant women had a downward trend (χ 2trend = 9.37, P = 0.002), which was 11.1% (13/117) in 2021. In 2020, 117 counties in the province reached the IDD elimination standard, with a compliance rate of 100.0%. Conclusions:Since the implementation of the current salt iodine content standard for 10 years, the consumption rate of qualified iodized salt has gradually stabilized and remained at a high level, which can ensure that IDD is in a sustainable state of elimination in Shanxi Province, and the iodine nutrition of school-age children and pregnant women is generally at a suitable level. However, there are a certain number of counties with insufficient iodine nutrition of pregnant women. It is recommended to guide pregnant women to supplement iodine or set the average standard of salt iodine for pregnant women separately.

Acute ischemic stroke with large vessel occlusion (AIS-LVO) refers to ischemic stroke caused by large vessel occlusion of internal carotid artery, middle cerebral artery and vertebrobasilar artery, which has the characteristics of large infarct, relatively poor outcome, higher disability and mortality. Therefore, early vascular recanalization and rescue of ischemic penumbra are the key to improve the outcome of patients with AIS-LVO. Mechanical thrombectomy (MT) has a definite effect on AIS-LVO. The current guidelines recommend that MT should be performed on the basis of IVT for AIS-LVO patients without contraindications of intravenous thrombolysis (IVT), the so-called bridging therapy. IVT can increase the risk of bleeding to a certain extent, delay MT and increase the cost of hospitalization. However, there are still many controversies about whether the patients with AIS-LVO can directly perform MT. This article reviews the comparative study of direct MT and bridging therapy in patients with anterior circulation AIS-LVO, hoping to provide reference for clinicians in the treatment of AIS-LVO.