Salivary gland tumor is one of the most common tumors in oral and maxillofacial regions. The diagnosis and treatment of salivary gland tumors had been a clinical characteristic project in Peking University School and Hospital of Stomatology since long time ago. Here we introduced the research progress in diagnosis and treatment of salivary gland tumors during the past 10 years. Among 7 190 cases of salivary gland tumors treated in this institution, 4 654 cases (64.7%) were benign, and 2 536 (35.3%) were malignant, with benign ∶ malignant ratio of 1.84 ∶ 1. Parotid was the most common location, followed by minor salivary gland and submandibular gland, while sublingular gland tumor was seldom seen. The proportion of minor salivary gland tumor was relatively high. Among 1 874 cases with primary malignant tumors, the cases with T3 and stage Ⅲ accounted for only 9.6% and 10.3%, respectively, which indicated that there was shortcoming in the T classification and clinical stage formulated by Union for International Cancer Control (UICC), and further revision was required. The 5, 10, and 15 year survival rates of 1 637 cases with postoperative follow-up were 93.1%, 87.2% and 79.3%, respectively, which were much higher than those we reported 30 years ago. The improvement of treatment results was related to more widely used combined treatment with surgery and postoperative radiotherapy, and the increase in patients with early stage. Adenoid cystic carcinoma was the malignant tumor with high rate of distant metastasis. The 5 and 10 year survival rates of the patients with pulmonary metastasis were 76.2% and 51.8%, respectively, which indicated that the pulmonary metastatic carcinomas developed slowly. Recurrent rate of carcinoma ex pleomorphic adenoma was 46.7% after single treatment of sur-gery, while it decreased to 27.5% after combined theraphy with surgery and radiotherapy, indicating that postoperative radiotheraphy could reduce the recurrent rate effectively. The normal myoepithelial cells had the inhibiting role in the invasion and metastasis of carcinoma ex pleomorphic adenoma. The evaluation of integrity of myoepithelial cells surrounding the tumor mass is helpful to understand the invasiveness of the tumors. The new surgical modalities such as extracapsular resection and partial sialoadenectomy were used in treatment of benign tumors of parotid gland and submandibular gland with advantages of decreased tissue damage and preservation of glandular function. Application of digital surgical techniques such as mixed reality combined with surgical navigation and real-time three-dimensional holograms in the surgical treatment of parotid gland tumors showed the benifits of more safety and precision, and less tissue da-mage.
Humans ; Salivary Gland Neoplasms/pathology* ; Carcinoma, Adenoid Cystic/therapy* ; Adenoma, Pleomorphic/therapy* ; Neoplasm Staging

Tricellulin, a key tricellular tight junction (TJ) protein, is essential for maintaining the barrier integrity of acinar epithelia against macromolecular passage in salivary glands. This study aims to explore the role and regulatory mechanism of tricellulin in the development of salivary gland hypofunction in Sjögren's syndrome (SS). Employing a multifaceted approach involving patient biopsies, non-obese diabetic (NOD) mice as a SS model, salivary gland acinar cell-specific tricellulin conditional knockout (Tric^CKO) mice, and IFN-γ-stimulated salivary gland epithelial cells, we investigated the role of tricellulin in SS-related hyposalivation. Our data revealed diminished levels of tricellulin in salivary glands of SS patients. Similarly, NOD mice displayed a reduction in tricellulin expression from the onset of the disease, concomitant with hyposecretion and an increase in salivary albumin content. Consistent with these findings, Tric^CKO mice exhibited both hyposecretion and leakage of macromolecular tracers when compared to control animals. Mechanistically, the JAK/STAT1/miR-145 axis was identified as mediating the IFN-γ-induced downregulation of tricellulin. Treatment with AT1001, a TJ sealer, ameliorated epithelial barrier dysfunction, restored tricellulin expression, and consequently alleviated hyposalivation in NOD mice. Importantly, treatment with miR-145 antagomir to specifically recover the expression of tricellulin in NOD mice significantly alleviated hyposalivation and macromolecular leakage. Collectively, we identified that tricellulin deficiency in salivary glands contributed to hyposalivation in SS. Our findings highlight tricellulin as a potential therapeutic target for hyposecretion, particularly in the context of reinforcing epithelial barrier function through preventing leakage of macromolecules in salivary glands.
Sjogren's Syndrome/complications* ; Animals ; Xerostomia/etiology* ; Mice ; Mice, Inbred NOD ; MARVEL Domain Containing 2 Protein/metabolism* ; Humans ; Mice, Knockout ; Disease Models, Animal ; Interferon-gamma ; Salivary Glands/metabolism* ; Tight Junctions/metabolism* ; MicroRNAs/metabolism* ; Female

Fabry disease, a rare genetic disorder affecting multiple organs, has understudied correlations among enzyme activity, genotype, and clinical manifestations in patients of different sexes with classical and late-onset phenotypes. In this study, clinical data, α-Gal A activity, and GLA gene test results of 311 patients, who were categorized by classical and late-onset phenotypes, ⩽5% and > 5% of the normal mean value of enzyme activity, and truncated and nontruncated mutation groups, were collected. The common clinical manifestations of Fabry disease included acroparesthesia, hypohidrosis/anhidrosis, neuropsychiatric system, and renal and cardiovascular involvement. Multiorgan involvement was higher in males and classical phenotype patients. In both sexes, classical patients commonly presented with acroparesthesia and multiorgan involvement, whereas late-onset patients showed renal, neuropsychiatric, and cardiovascular involvement. Male and classical patients had lower enzyme activity than female and late-onset patients, respectively. Classical males with enzyme activity of ⩽5% of the normal mean level showed higher multiorgan involvement frequency than those with enzyme activity of > 5%, whereas no significant difference was observed among females. Ninety-five gene mutation sites were detected, with significant phenotype heterogeneity in patients with the same mutation. No significant difference in enzyme activity or clinical manifestations was observed between truncated and nontruncated mutations. Overall, male patients with Fabry disease, regardless of classical or late-onset phenotype, have a higher frequency of multiple-organ involvement and lower α-Gal A activity than female patients. α-Gal A activity was closely correlated with clinical symptoms in males but weakly correlated with clinical manifestations in females. The clinical manifestations of patients with the same mutation are heterogeneous, and the correlation between gene mutation and enzyme activity or clinical manifestation is weak.
Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Age of Onset ; alpha-Galactosidase/metabolism* ; China ; Fabry Disease/enzymology* ; Genotype ; Mutation ; Phenotype ; Sex Factors ; East Asian People/genetics*

Objective:To improve the teaching quality of Medical Microbiology by optimizing the teaching method,adjusting the teaching content and reforming the assessment model.Methods:The students of grade 2020 and 2021 of the same major were divided into the control group and the reform group.The control group received the traditional teaching method.The reform group received the"online + offline"blended teaching method,which integrates online learning resources and ideological and political education into the theoretical content of the curriculum.And the whole process assessment system was applied to the teaching method.The teaching quality was evaluated by the whole process examination results and questionnaire survey.Results:Compared with the control group,the score in the reform group was significantly improved(P＜0.01).Results of the questionnaire survey showed that students'satisfaction with the mixed teaching method reached 97.5% .The integration of hot issues of microbiology and curriculum ideological and political education significantly improved students'learning interest,and more students wanted to engage in the work of microbiology related fields in the future.Conclusion:The practice results show that optimizing the teaching method,adjusting the teaching content and reforming the assessment mode can stimulate the students'learning interest,improve the students'independent learning ability and improve the teaching quality.

Objective:To explore the value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) parameters in different regions of the kidney in distinguishing IgA nephropathy (IgAN) patients from healthy volunteers.Methods:This study was a cross-sectional study. Eighty-four patients diagnosed with IgAN (IgAN group) who underwent renal biopsy (lower pole of the left kidney) and were pathologically confirmed at the First Medical Center of PLA General Hospital from February 2022 to September 2023 and thirty-four healthy volunteers (control group) were included prospectively. The regions of interest were outlined in the right renal cortex, medulla, and parenchyma for all subjects, and the apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D *), and perfusion fraction (f) were measured in the corresponding regions. The differences in IVIM-DWI parameters between the IgAN group and the control group were compared using the student′s t-test or the Mann-Whitney U test. Receiver operating characteristic curve analysis was performed on the parameters with statistically significant differences, and the area under the curve (AUC) was calculated. Results:There were statistically significant differences in renal cortical ADC, renal parenchymal ADC, renal cortical D, renal parenchymal D, and renal medullary f values between the IgAN group and the control group ( Z=-3.03, -2.21, -2.62, -2.03, -2.03; P=0.002, 0.027, 0.009, 0.043, 0.042). The AUCs (95% CI) for diagnosing IgAN using renal cortical ADC, renal parenchymal ADC, renal cortical D, renal parenchymal D, and renal medullary f values were 0.679 (0.586-0.762), 0.630 (0.537-0.717), 0.654 (0.535-0.774), 0.619 (0.497-0.742), and 0.620 (0.495-0.745), respectively. There were no statistically significant differences in renal medullary ADC, D, renal cortex, medulla and parenchyma D *, renal cortical and renal parenchymal f values between the two groups ( P>0.05). Conclusion:The quantitative parameters of renal IVIM-DWI are influenced by different measurement regions, among which the ADC, D of renal cortex and parenchyma, and f of renal medulla can be used for the initial diagnosis of IgAN.

ObjectiveTo identify the chemical components of Houpo Wenzhongtang in vivo and in vitro and to analyze the pharmacokinetic properties of the index components in rats with deficiency-cold of spleen and stomach. MethodThe chemical components of Houpo Wenzhongtang was analyzed and identified by ultra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS/MS）. Six rats were randomly selected from 18 SD rats as the blank group， and the remaining rats were given lard and cold vinegar for a long time to construct a rat model with deficiency-cold of spleen and stomach. After successful modeling， the rats were randomly divided into the model group and Houpu Wenzhongtang group（13.5 g·kg^-1， calculated as crude drug）. The administration group was given the corresponding dose of Houpu Wenzhongtang by gavage， and the blank group and the model group were given the same amount of distilled water by gavage. Enzyme-linked immunosorbent assay（ELISA） were used to measure gastrin（GAS） and motilin（MTL） levels in each group. At the same time， plasma samples were collected at different time points after administration， and blood-entry prototype components and metabolites of Houpo Wenzhongtang were analyzed by UPLC-Q-TOF-MS/MS. On this basis， plasma concentrations of magnolol， honokiol， alpinetin and hesperidin in Houpo Wenzhongtang were determined by ultra performance liquid chromatography coupled with triple quadrupole/linear ion trap mass spectrometry（UPLC-QTRAP-MS/MS）， and the pharmacokinetic parameters were calculated using DAS 2.0 software. ResultA total of 79 chemical components， including 44 flavonoids and 11 lignans， were identified in Houpo Wenzhongtang. Meanwhile， 18 blood-entry prototype components and 27 metabolites were identified， the main metabolic pathways of metabolites were glucuronidation， sulfation， oxidation and hydrolysis， and phase Ⅰ and phase Ⅱ were the two primary forms of metabolism. Pharmacokinetic results showed that among the four index components， the time to peak（t_max） values of magnolol and honokiol were consistent and exhibited similar drug metabolism characteristics， the t_max of alpinetin was the shortest， and the absorption rate was the fastest， which had the earliest peak plasma concentration levels， and hesperidin had the shortest mean residence time（MRT_0-t） and the highest metabolic rate in rats. ConclusionThis study clarifies the blood-entry prototype components and their metabolites of Houpo Wenzhongtang in the rat model of deficiency-cold of spleen and stomach， and reveals the pharmacokinetic characteristics of the main active ingredients， which can provide a scientific basis for the study of pharmacodynamic material basis of this formula and its clinical application in treating the syndrome of deficiency-cold of spleen and stomach.

Objective:To investigate the effects of low-frequency and high frequency repetitive transcranial magnetic stimulation (rTMS) combined with levodopa and benserazide hydrochloride on mild cognitive impairment in patients with Parkinson disease (PD).Methods:Totally 90 PD patients with mild cognitive impairment who visited from January 2020 to June 2022 were included , and they were divided into a simple drug group ( n=30), drug+ low-frequency group ( n=30), and drug+ high-frequency group ( n=30) according to the order of admission.The patients in the simple drug group were treated with oral levodopa and benserazide hydrochloride, while the patients in drug+ low-frequency and drug+ high-frequency groups were treated with low-frequency or high-frequency rTMS on the basis of oral levodopa and benserazide hydrochloride.Montreal cognitive assessment(MoCA), digital span (DS), Chinese auditory learning test (CALT), the judgment of line orientation test (JLOT) and verbal fluency test (VFT) were used to evaluate the cognitive function of patients before and after 4 weeks of treatment.SPSS 26.0 was used for statistical analysis.The paired t-test was used for intra-group comparison before and after treatment, while one-way ANOVA was used for inter-group comparison. Results:There were no significant differences in MoCA, DS anterograde, DS backward, CALT immediate recall, CALT delayed recall, JLOT, and VFT scores among patients in the simple drug group before and after 4 weeks of treatment( t=-1.157, -0.648, -0.215, -0.290, -0.154, -0.782, -0.960, all P>0.05). After 4 weeks of treatment, MoCA, DS anterograde, DS backward, CALT immediate recall, CALT delayed recall, JLOT and VFT scores in drug+ low-frequency group and drug+ high-frequency group were higher than before treatment (drug+ low frequency group: t=-16.357, -11.379, -7.999, -11.805, -16.624, -15.996, -17.241, all P<0.05; drug+ high-frequency group: t=-25.198, -13.971, -13.904, -25.831, -26.382, -20.108, -15.643, all P<0.05). There were no statistically significant differences in the scores of MoCA, DS anterograde, DS backward, CALT immediate recall, CALT delayed recall, JLOT and VFT among the three groups before treatment (all P>0.05). After treatment, there were statistically significant differences in the scores of MoCA, DS anterograde, DS backward, CALT immediate recall, CALT delayed recall, JLOT and VFT among the three groups (simple drug group : (20.37±1.96), (4.37±1.19), (2.80±0.55), (6.93±1.70), (5.17±1.09), (15.50±2.69), (10.73±1.55); drug+ low-frequency group: (23.83±2.32), (5.87±0.94), (3.87±0.73), (9.17±1.74), (8.13±1.50), (20.77±2.19), (13.30±1.73); drug+ high-frequency group: (27.17±1.64), (6.73±1.01), (4.80±0.81), (11.20±2.06), (10.03±1.54), (25.17±3.14), (15.87±2.05)) (all P<0.05). Further analysis showed that both the drug+ low-frequency and drug+ high-frequency groups had higher scores than the simple drug group, and the drug+ high-frequency group had higher scores than the drug+ low-frequency group(all P<0.05). Conclusion:The combination of drug+ low-frequency or drug+ high-frequency rTMS and drug therapy can help improve cognitive function in patients with PD, and the efficacy of drug+ high-frequency rTMS may be more significant, which provides a new therapeutic idea for clinical treatment of patients with PD.

OBJECTIVE To systematically evaluate the efficacy and safety of transcatheter arterial chemoembolization （TACE） combined with anti-angiogenic drugs for the treatment of unresectable primary liver cancer （PLC）. METHODS Retrieved from Chinese and English databases such as CNKI， the Cochrane Library， Google， and Baidu Academic， randomized controlled trial （RCT） about TACE combined with anti-angiogenic drugs for the treatment of unresectable PLC were collected from the inception to May 27， 2024. After screening the literature， extracting data， and evaluating the quality of the literature， network meta-analysis was performed using R 4.2.2 and Stata 17.0. RESULTS A total of 44 RCT were included， involving 5 607 patients and 8 interventions. The network meta-analysis results showed that for prolonging median overall survival （mOS） and median progression- free survival （mPFS）， TACE+apatinib had the best efficacy， with TACE+apatinib and TACE+sorafenib ranking as the top two. For improving objective response rate （ORR） and disease control rate （DCR）， TACE+donafenib had the best efficacy， with TACE+ donafenib and TACE+ lenvatinib ranking as the top two. In terms of safety， TACE+donafenib was the best， with TACE+donafenib and TACE+apatinib ranking as the top two. CONCLUSIONS TACE+apatinib and TACE+donafenib have good efficacy for patients with unresectable PLC， and TACE+donafenib has the best safety profile.

In order to achieve the goal of integration, homogeneity, a net and a center of medical groups in Hainan province, Hainan province built an integrated management information platform of urban medical alliances and county medical communities based on projects such as the provincial three medical linkage information platform in February 2022. The overall architecture of the medical alliance and medical community platform was divided into system integration layer, data center layer, service layer and application layer. The service layer included four major systems: unified operation management platform, business center, performance evaluation management platform and comprehensive supervision subsystem, which was the core hub connecting the data center layer and application layer, and also was the unified operation and closed-loop management platform of the medical alliance and medical community. As of November 2022, the platform had covered 31 medical alliances or medical communities in 19 cities and counties of Hainan province, achieving information exchange, personnel interaction, resource sharing, business collaboration, and data integration among member units, narrowing the gap between urban and rural medical and health services, which had preliminarily achieved homogeneous management of the medical alliances and medical communities throughout the province, for a reference for the integrated management of medical alliances and medical communities within the regional scope of China.

CRISPR-Associated Protein 9 ; Gene Editing ; CRISPR-Cas Systems/genetics*