The construction of a training system for visiting physicians in the department of rare diseases in China is an important measure to improve the overall diagnosis and treatment capacity for rare diseases and address the critical challenge of insufficient knowledge and skills among clinicians in practice. This article systematically describes the visiting physician training system established by the Department of Rare Diseases at Peking Union Medical College Hospital. It summarizes the training objectives and positioning, design logic, and learning modules of the system, aiming to provide a reference for the construction of the specialized talent team for rare diseases in China.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

OBJECTIVE: To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL). METHODS: A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01). RESULTS: The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P = 0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P < 0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients (P = 0.002), while TP53 (P = 0.024) and BCL2 (P = 0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years (HR = 3.439, 95%CI: 1.318~9.874), presence of B symptoms (HR = 2.871, 95%CI = 1.133~7.307), and elevated lactate dehydrogenase (HR = 3.528, 95%CI = 1.231~10.66) as independent adverse prognostic factors. CONCLUSION Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Middle Aged ; Female ; Male ; Retrospective Studies ; Aged ; Prognosis ; Adult ; Aged, 80 and over ; High-Throughput Nucleotide Sequencing ; Young Adult ; Adolescent ; Genetic Variation

Objective To analyze the influencing factors of chronic obstructive pulmonary disease(COPD)complicating pulmonary interstitial fibrosis,and to establish a nomogram prediction model.Methods The clinical data of 195 patients with COPD admitted and treated in this hospital from January 2019 to Feb-ruary 2021 were retrospectively analyzed.The factors possibly affecting the patients with COPD complicating pulmonary interstitial fibrosis were collected,and the patients were divided into 2 groups according to whether having pulmonary interstitial fibrosis.The independent risk factors were analyzed and screened by the multi-variate logistic regression.Then the nomogram prediction model was constructed.Results Among the includ-ed 195 cases of COPD in this study,there were 50 cases(25.64％)of complicating pulmonary interstitial fi-brosis.The univariate and multivariate logistic regression analysis results showed that the smoking history,duration of COPD,frequency of acute exacerbations onset,serum transforming growth factor β1(TGF-β1),basic fibroblast growth factor(bFGF)and angiotensin Ⅱ(AngⅡ)were the independent influencing factors of COPD complicating pulmonary interstitial fibrosis(P＜0.05).The nomogram model was constructed accord-ing to the results of multivariate analysis results,and the area under the receiver operating characteristic(ROC)curve was 0.956(95％CI:0.930-0.983),the average absolute error of internal verification by the Bootstrap method was 0.025,and the prediction model performance basically fitted the ideal model.Conclusion The nomogram model constructed by this study for predicting the pulmonary interstitial fibrosis in COPD patients has high accuracy and distinction degree.

Thrombocytopenia is one of the common complications of cirrhotic patients, which can induce an increasing bleeding risk and closely correlate with bleeding following invasive procedures. Consequently, how to respond to thrombocytopenia is crucial for improving the prognosis of patients with cirrhosis. This article reviews the main mechanisms of cirrhosis concurrent with thrombocytopenia, as well as the corresponding clinical management strategies.

Objective:To investigate effect of Yiqi Huoxue Huazhuo Jiedu Prescription(YHHJP)on inflammatory factors of brain tissues,tight junction between brain and colon tissues,intestinal flora and bacterial metabolites in cerebral ischemia reperfusion injury(CIRI)rats based on brain-gut axis.Methods:Fifty male SD rats of SPF grade were randomly divided into sham-operation group(Sham),model group(MCAO),low,medium,high doses YHHJP groups(TCM-L/TCM-M/TCM-H).Middle cerebral artery occlusion model was established according to Zea Longa methods.Neurological function defects were detected 3 days after administra-tion.TTC staining was used to calculate infarct size of brain tissue.Pathological changes of brain tissue were observed by Nissl staining,and pathological changes of brain and colon tissues were observed by HE staining.IL-1β,IL-6,TNF-α in brain tissue and LPS con-tent in serum were detected by ELISA,and D-LA content in serum was detected by biochemical method.Gene expressions of ZO-1 and Claudin-5 in brain tissue and gene expressions of ZO-1,Claudin-1 in colon tissue were studied by Real-time fluorescent quantita-tive PCR.Intestinal flora were detected by 16S rDNA high-throughput sequencing.Results:Compared with Sham group,pathological damage of brain and colon tissue were serious in MCAO group,intestinal flora structure was significantly different,neural function im-pairment was aggravated,infarct size was increased,IL-1β,IL-6,TNF-α contents in brain tissue,and LPS,D-LA contents in serum were increased,gene expressions of ZO-1 and Claudin-5 in brain tissue and gene expressions of ZO-1 and Claudin-1 in colon tissue were decreased significantly(P<0.05).Compared with MCAO group,pathological damage of brain and colon tissue of rats were relieved in TCM-L,TCM-M,TCM-H groups,disturbance of intestinal microflora microecology was improved,neurological function impairment and infarct size were markedly decreased,IL-1β,IL-6,TNF-α contents in brain tissue were decreased,gene expressions of ZO-1 and Claudin-1 in colon tissue were increased significantly(P<0.05);LPS and D-LA contents in serum were decreased in YH-HJP medium and high doses groups,while gene expressions of ZO-1 and Claudin-5 in brain tissue were increased significantly(P<0.05).Conclusion:YHHJP has a good effect on improving CIRI,whose mechanism may be related to regulating diversity of intestinal flora,reducing release of intestinal bacterial metabolites LPS and D-LA,increasing gene expressions of tight junction proteins ZO-1,Claudin-5 and Claudin-1,and down-regulating secretion of proinflammatory cytokine.

Objective To develop a Behavioral Decision-making Scale for Glycemic Management in pregnant women with gestational diabetes and to test its reliability and validity.Methods Based on the trans-theoretical model and behavioral decision theory,the test version of the scale was formed through literature review,semi-structured interview,brainstorming,2 rounds of expert consultation and cognitive interview.A total of 560 pregnant women with gestational diabetes mellitus were recruited from 10 hospitals in Quanzhou,Fujian Province by convenience sampling method from 21 July to November 2023.The data were divided into 2 parts by random number method for exploratory factor analysis and confirmatory factor analysis.Results The scale included 4 dimensions of"behavioral decision-making motivation""behavioral decision-making influencing factors""behavioral decision-making intention"and"behavioral decision-making effectiveness"with 34 items.The Cronbach's αcoefficient of the total scale was 0.971;the split-half reliability was 0.919;the test-retest reliability was 0.863;the content validity index of the scale was 0.853.The exploratory factor analysis extracted 4 common factors,and the cumulative variance contribution rate was 78.28％.The confirmatory factor analysis showed that the factor structure of the scale was stable.Conclusion The scale has ideal reliability and validity,which can be used to measure the level of glycemic management behavior decision-making of pregnant women with gestational diabetes mellitus.

About 40% of approved drugs and nearly 90% of drug candidates are poorly water-soluble drugs. Low solubility reduces the drugability. Effectively improving the solubility and bioavailability of poorly water-soluble drugs is a critical issue that needs to be urgently addressed in drug development and application. This review briefly introduces the conventional solubilization techniques such as solubilizers, hydrotropes, cosolvents, prodrugs, salt modification, micronization, cyclodextrin inclusion, solid dispersions, and details the crystallization strategies, ionic liquids, and polymer-based, lipid-based, and inorganic-based carriers in improving solubility and bioavailability. Some of the most commonly used approved carrier materials for solubilization techniques are presented. Several approved poorly water-soluble drugs using solubilization techniques are summarized. Furthermore, this review summarizes the solubilization mechanism of each solubilization technique, reviews the latest research advances and challenges, and evaluates the potential for clinical translation. This review could guide the selection of a solubilization approach, dosage form, and administration route for poorly water-soluble drugs. Moreover, we discuss several promising solubilization techniques attracting increasing attention worldwide.

The secondary motor cortex (M2) encodes choice-related information and plays an important role in cue-guided actions. M2 neurons innervate the dorsal striatum (DS), which also contributes to decision-making behavior, yet how M2 modulates signals in the DS to influence perceptual decision-making is unclear. Using mice performing a visual Go/No-Go task, we showed that inactivating M2 projections to the DS impaired performance by increasing the false alarm (FA) rate to the reward-irrelevant No-Go stimulus. The choice signal of M2 neurons correlated with behavioral performance, and the inactivation of M2 neurons projecting to the DS reduced the choice signal in the DS. By measuring and manipulating the responses of direct or indirect pathway striatal neurons defined by M2 inputs, we found that the indirect pathway neurons exhibited a shorter response latency to the No-Go stimulus, and inactivating their early responses increased the FA rate. These results demonstrate that the M2-to-DS pathway is crucial for suppressing inappropriate responses in perceptual decision behavior.
Mice ; Animals ; Motor Cortex ; Corpus Striatum/physiology* ; Neostriatum ; Neurons/physiology* ; Reaction Time

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).