ObjectiveTo investigate the etiology and clinical features of intrahepatic cholestasis and the diagnostic value of whole exome sequencing （WES） through a retrospective analysis of the medical history， pathological results， and gene sequencing data of 62 patients with unexplained intrahepatic cholestasis. MethodsA retrospective analysis was performed for the clinical data of 480 patients who underwent WES due to unexplained liver function abnormalities in Nanjing Second Hospital from January 2017 to December 2023， among whom 62 patients with unexplained intrahepatic cholestasis were selected based on laboratory data， and a confirmed diagnosis was made based on imaging data， pathological findings， and gene sequencing data. The patients with unexplained intrahepatic cholestasis were analyzed in terms of demographic features， clinical manifestation， etiology spectrum， and genetic profile. ResultsA total of 62 patients with unexplained intrahepatic cholestasis were included， among whom there were 35 male patients and 27 female patients， with a median age of 42 （7 — ‍77） years. WES was used to make a definite diagnosis in 21 patients （33.87%）， among whom the patients with familial intrahepatic cholestasis accounted for the highest proportion of 52.38% （11/21）； genetic metabolic disorders were excluded by WES in 34 patients， with drug-induced liver injury and sepsis-associated liver injury accounting for the highest proportion of 55.88% （19/34）， followed by primary biliary cholangitis and primary sclerosing cholangitis accounting for 20.59% （7/34） and intrahepatic bile duct stones accounting for 17.65% （6/34）， while the patients with a lack of confirmed diagnosis accounted for 11.29% （7/62）. A total of 21 novel mutation sites which were not reported in previous articles were identified in this study. ConclusionGenetic metabolic disorders constitute a significant proportion of unexplained intrahepatic cholestasis， and WES plays a crucial role in the diagnosis of unexplained intrahepatic cholestasis.

ObjectiveTo investigate the awareness and clinical practice of guidelines for the prevention and treatment of chronic hepatitis B （2022 edition） among clinicians. MethodsFrom July 19 to December 31， 2024， a self-designed electronic questionnaire was distributed via the WeChat mini program to collect related data from 1 588 clinicians nationwide， including their awareness and practice based on 18 questions regarding testing and referral， diagnosis and treatment， and follow-up. ResultsAmong all respondents， only 350 clinicians correctly understood all the updated key points of antiviral indications and treatment for special populations in the 2022 edition of guidelines for the prevention and treatment of chronic hepatitis B， with an overall awareness rate of 22.0%. Only 20% ‍—‍ ‍40% of the patients with positive HBV DNA and an age of >30 years receive antiviral therapy， while 80% ‍—‍ ‍100% of the patients with positive HBV DNA and a family history of hepatitis B cirrhosis or hepatocellular carcinoma receive antiviral therapy. The median follow-up rates at 1 year， 3 years， and 5 years were 67.5% 57.5% and 47.5%，respectively， showing a trend of gradual reduction， which might be associated with the influencing factors such as insufficient time for follow-up management by clinicians， insufficient awareness of the disease among patients， and poor adherence to follow-up. ConclusionThere is a gap between the awareness and practice of guidelines for the prevention and treatment of chronic hepatitis B （2022 edition） among clinicians. It is recommended to further strengthen training and focus on the whole process of “detection， diagnosis， treatment， and management” for patients with chronic hepatitis B in healthcare institutions， in order to promote the implementation of the guidelines.

[This corrects the article DOI: 10.1016/j.apsb.2019.01.013.].

Venous system diseases mainly include varicose veins and venous malformations of lower limbs and the genital system. Most of them are chronic diseases that cause serious clinical symptoms to patients and affect their health and quality of life. Sclerotherapy has become the first-line therapy for venous system diseases. However, there are problems such as incomplete fibrosis and vascular recanalization after sclerotherapy, and improper operation will cause serious adverse consequences. Therefore, exploring a safe and effective sclerotherapy strategy is essential for developing clinically successful sclerotherapy. To solve the above problems, we proposed a new sclerotherapy strategy with a dual mechanism of "vascular damage and plasmin (PLA) system inhibition." We intended to construct a novel cationic surfactant (AEO_x-TA) by reacting tranexamic acid (TA), a parent structure, with fatty alcohol polyoxyethylene ether (AEO_x) by ester bonds. AEO_x-TA could damage vascular endothelium and initiate a coagulation cascade effect to induce thrombus. Furthermore, AEO_x-TA could be degraded by esterase and release the parent drug, TA, which could inhibit the PLA system to inhibit the degradation of thrombus and extracellular matrix and promote the process of vascular fibrosis. In addition, such surfactant-based sclerosants have foam-forming properties, and they can be blended with polyvinyl alcohol (PVA) to prepare a highly stable foam formulation (AEO_x-TA/P), which can achieve a precise drug delivery and prolonged drug retention time, thereby improving drug efficacy and reducing the risk of ectopic embolism. Overall, the novel cationic surfactant AEO_x-TA provides a new avenue to resolve the bottleneck: surfactant sclerosants' efficiency is relatively low in the current sclerotherapy.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

ObjectiveTo analyze the changing trend of the disease burden of acute viral hepatitis （AVH） globally and in China from 1990 to 2021， and to provide a basis for optimizing prevention and control strategies. MethodsRelated data were extracted from the Global Burden of Disease 2021 database， including incidence rate， mortality rate， and disability-adjusted life years （DALY） for AVH globally and in China from 1990 to 2021， and the patients were divided into groups according to region， age， sex， and type of hepatitis. The Joinpoint regression model was used to calculate average annual percentage change （AAPC） and its 95% confidence interval （CI）. ResultsFrom 1990 to 2021， there was a tendency of reduction in the age-standardized incidence rate， mortality rate， and DALY rate of AVH globally， with an average annual reduction of 1.02% （95%CI： -1.10% to -0.94%， P<0.001）， 3.97% （95%CI： -4.12% to -3.82%， P<0.001）， and 3.64% （95%CI： -3.84% to -3.44%， P<0.001）， respectively； in China， there was also a tendency of reduction in these indicators， with an average annual reduction of 1.63% （95%CI： -1.70% to -1.57%， P<0.001）， 9.24% （95%CI： -9.51% to -8.97%， P<0.001）， and 7.93% （95%CI： -8.15% to -7.71%， P<0.001）， respectively. In addition， China’s share of the global disease burden of AVH continued to decrease； the proportion of new cases decreased from 24% in 1990 to 15% in 2021， the proportion of deaths decreased from 19% to 4%， and the proportion of DALY decreased from 16% to 4%. From 1990 to 2021 globally， the peaks in the incidence rate， mortality， and DALY of AVH were observed in children under 5 years of age； in China， although the peak incidence rate of the disease was still observed in children under 5 years of age， there was a tendency of increase in the incidence rate of AVH among young adults aged 25 — 29 years in recent years， with the most significant increase in the cases of acute hepatitis B （accounting for 59% of the cases in this age group）， while the disease burden of mortality and DALY mainly affected the middle-aged and elderly populations. The disease burden of AVH in the male population was higher than that in the female population. As for the distribution of disease types， acute hepatitis A was the predominant type of AVH， accounting for 64% globally and 48% in China， whereas acute hepatitis B was the leading cause of mortality and DALY， accounting for 50% of deaths globally， 80% of deaths in China， 47% of DALY globally， and 69% of DALY in China. ConclusionThere is a tendency of reduction in the disease burden of AVH globally and in China from 1990 to 2021， but there is a tendency of increase in the incidence rate of AVH among young adults in China， especially acute hepatitis B. It is necessary to implement targeted prevention and control strategies.

Virus-like particles (VLPs) are self-assembled protein nanoparticles with repetitive antigen epitopes, which can stimulate immune response and do not contain viral genetic materials. VLPs has important research value and application potential in vaccine development, targeted drug delivery and bioengineering materials. In this review, the mechanism of VLPs vaccine induced immune responses is discussed. The existing VLPs expression systems are summarized. The research progress of VLPs vaccine in prevention and treatment of virus infection are summarized. This review provides general reference and guidance for the design and development of antiviral VLPs vaccine.

Virus-like particles (VLPs) are self-assembled protein nanoparticles with repetitive antigen epitopes, which can stimulate immune response and do not contain viral genetic materials. VLPs has important research value and application potential in vaccine development, targeted drug delivery and bioengineering materials. In this review, the mechanism of VLPs vaccine induced immune responses is discussed. The existing VLPs expression systems are summarized. The research progress of VLPs vaccine in prevention and treatment of virus infection are summarized. This review provides general reference and guidance for the design and development of antiviral VLPs vaccine.

ObjectiveThis study aims to examine the effect of Rhei Radix et Rhizoma-Coptidis Rhizoma on reducing insulin resistance in db/db mice by regulating the adenylate activated protein kinase （AMPK）/UNC-51-like kinase 1 （ULK1）/key molecule of autophagy， benzyl chloride 1 （Beclin1） pathway and elucidate the underlying mechanism. MethodSixty 6-week-old male db/db mice were studied. They were randomly divided into the model group， metformin group （0.26 g·kg^-1）， and low-， middle-， and high-dose groups （2.25， 4.5， 9 g·kg^-1） of Rhei Radix et Rhizoma-Coptidis Rhizoma. A blank group of db/m mice of the same age was set， with 12 mice in each group. After eight weeks of continuous intragastric administration， the blank group and model group received distilled water intragastrically once a day. The survival status of the mice was observed， and fasting blood glucose （FBG） was measured using a Roche blood glucose device. Fasting serum insulin （FINS） was measured using an enzyme-linked immunosorbent assay， and the insulin resistance index （HOMA-IR） was calculated. Hematoxylin-eosin （HE） staining was performed to observe the pathological changes in the liver of the mice. The protein expression levels of AMPK， Beclin1， autophagy associated protein 5 （Atg5）， and p62 in liver tissue were determined by using Western blot. The protein expression levels of autophagy associated protein 1 light chain 3B （LC3B） and ULK1 in liver tissue were determined using immunofluorescence. Real-time fluorescence quantitative PCR （Real-time PCR） was used to measure mRNA expression levels of AMPK， Beclin1， Atg5， ULK1， and p62. ResultCompared with the blank group， the model group exhibited a significant increase in body mass （P<0.01）. Additionally， the levels of FBG， FINS， and HOMA-IR significantly changed （P<0.01）. The structure of liver cells was disordered. The protein expression levels of AMPK， Beclin1， and Atg5 in liver tissue were significantly decreased （P<0.01）， while the expression level of p62 protein was significantly increased （P<0.01）. The expression levels of mRNA and proteins were consistent. Compared with the model group， the body mass of the metformin group and high and medium-dose groups of Rhei Radix et Rhizoma-Coptidis Rhizoma was significantly decreased （P<0.05）. FBG， FINS， and HOMA-IR were significantly decreased （P<0.05，P<0.01）. After treatment， the liver structure damage in each group was alleviated to varying degrees. The protein expressions of AMPK， Beclin1， Atg5， LC3B， and ULK1 were increased （P<0.05，P<0.01）， while the protein expression of p62 was decreased （P<0.01）. The expression levels of mRNA and proteins were generally consistent. ConclusionThe combination of Rhei Radix et Rhizoma-Coptidis Rhizoma can effectively improve liver insulin resistance， regulate the AMPK autophagy signaling pathway， alleviate insulin resistance in db/db mice， and effectively prevent the occurrence and development of type 2 diabetes.

Fibromyalgia syndrome （FMS） is a refractory， chronic non-articular rheumatic disease characterized by widespread pain throughout the body， for which there are no satisfactory therapeutic drugs or options. There are rich Chinese medical therapies， and some non-drug therapies， such as acupuncture， Tai Chi， and Ba-Duan-Jin， have shown satisfactory efficacy and safety and definite advantages of simultaneously adjusting mind and body. FMS is taken as a disease responding specifically to traditional Chinese medicine （TCM） by the National Administration of Traditional Chinese Medicine in 2018. In order to clarify the research progress in FMS and the clinical advantages of TCM/integrated Chinese and Western medicine， the China Academy of Chinese Medicine organized a seminar for nearly 20 experts in Chinese and Western medicine， including rheumatology， psychology， acupuncture and moxibustion， and encephalopathy， with the topic of difficulties in clinical diagnosis and treatment of FMS and advantages of TCM and Western medicine. The recommendations were reached on the difficulties in early diagnosis and solutions of FMS， mitigation of common non-specific symptoms， preferential analgesic therapy， TCM pathogenesis and treatment advantages， and direction of treatment with integrated Chinese and Western medicine. FMS is currently facing the triple dilemma of low early correct diagnosis， poor patient participation， and unsatisfactory benefit from pure Western medicine treatment. To solve the above problems， this paper suggests that rheumatologists should serve as the main diagnostic force of this disease， and they should improve patient participation in treatment decision-making， implement exercise therapy， and fully utilize the holistic and multidimensional features of TCM， which is effective in alleviating pain， improving mood， and decreasing adverse events. In addition， it is suggested that FMS treatment should rely on both TCM and Western medicine and adopt multidisciplinary joint treatment， which is expected to improve the standard of diagnosis and treatment of FMS in China.