Mycobacterium tuberculosis ( Mtb) is the causative agent of tuberculosis in humans and animals. Mtb invades the host′s lungs via airborne transmission, infects macrophages and causes tuberculosis. In some cases, the infection can spread to other tissues and organs. Despite the availability of several drugs for the treatment of tuberculosis, the emergence of multi-drug-resistant tuberculosis has led to high morbidity and mortality rates worldwide. Therefore, there is an urgent need for researchers to develop new anti-tuberculosis drugs that can treat tuberculosis more efficiently. Recent studies have shown that the virulence factors of Mtb play a crucial role in its pathogenicity. These factors primarily include secreted proteins, transcription factors, proteases, stress response proteins, metabolism-associated proteins, and cell-surface components. By evading the host′s immune surveillance through mechanisms such as anti-oxidative stress, regulating nutrient synthesis and metabolism, and modulating host cells apoptosis, Mtb is able to achieve long-term survival and spread with in the host. Understanding the mechanisms of Mtb virulence factors can provide new directions for targeted tuberculosis therapy. Therefore, knowledge of these virulence factors is essential for the development of new vaccines and anti-tuberculosis drugs. In this review, we summarize the latest research progress in the virulence factors of Mtb to provide a reference for targeted treatment of tuberculosis.

OBJECTIVES: To investigate the expression of apolipoprotein C1 (APOC1) in papillary thyroid carcinoma (PTC) and its effects on proliferation and apoptosis of PTC cells. METHODS: The expression level of APOC1 in PTC and its impact on prognosis were analyzed using GEPIA 2 and Kaplan-Meier databases. Immunohistochemistry (IHC) and Western blotting were used to detect the expression of APOC1 in PTC and adjacent tissues and in 3 PTC cell lines and normal thyroid Nthyori 3-1 cells. In TPC-1 and BCPAP cells, the effect of Lipofectamine 2000-mediated transfection with APOC1 siRNA or an APOC1-overexpressing plasmid on cell growth and colony formation ability were examined by observing the growth curves and using colony-forming assay. The changes in cell cycle and apoptosis of the transfected cells were analyzed with flow cytometry. RT-qPCR and Western blotting were used to detect the changes in expressions of P21, P27, CDK4, cyclin D1, Bcl-2, Bax, caspase-3 and caspase-9 and the key proteins in the JAK2/STAT3 signaling pathway. RESULTS: APOC1 expression was significantly higher in PTC tissues and the 3 PTC cell lines than in the adjacent tissues and Nthyori 3-1 cells, respectively. In TPC-1 and BCPAP cells, APOC1 knockdown obviously reduced cell proliferative activity, increased the percentage of G0/G1 phase cells, lowered the percentages of S and G2 phase cells, promoted cell apoptosis, and downregulated mRNA and protein expression levels of CDK4, cyclin D1 and Bcl-2 and the protein levels of p-JAK2 and p-STAT3. APOC1 overexpression in the cells produced the opposite effects on cell proliferation, apoptosis, cell cycle and the mRNA and protein expressions. The application of AG490, a JAK2 inhibitor, strongly attenuated APOC1 overexpression-induced activation of the JAK2/STAT3 signaling pathway in BCPAP cells. CONCLUSIONS APOC1 overexpression promotes proliferation and inhibits apoptosis of PTC cells possibly by activating the JAK2/STAT3 signaling pathway and accelerating cell cycle progression.
Humans ; Apoptosis ; Cell Proliferation ; STAT3 Transcription Factor/metabolism* ; Signal Transduction ; Janus Kinase 2/metabolism* ; Thyroid Neoplasms/pathology* ; Thyroid Cancer, Papillary ; Cell Line, Tumor ; Carcinoma, Papillary

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*

Mycobacterium tuberculosis ( Mtb) is the causative agent of tuberculosis in humans and animals. Mtb invades the host′s lungs via airborne transmission, infects macrophages and causes tuberculosis. In some cases, the infection can spread to other tissues and organs. Despite the availability of several drugs for the treatment of tuberculosis, the emergence of multi-drug-resistant tuberculosis has led to high morbidity and mortality rates worldwide. Therefore, there is an urgent need for researchers to develop new anti-tuberculosis drugs that can treat tuberculosis more efficiently. Recent studies have shown that the virulence factors of Mtb play a crucial role in its pathogenicity. These factors primarily include secreted proteins, transcription factors, proteases, stress response proteins, metabolism-associated proteins, and cell-surface components. By evading the host′s immune surveillance through mechanisms such as anti-oxidative stress, regulating nutrient synthesis and metabolism, and modulating host cells apoptosis, Mtb is able to achieve long-term survival and spread with in the host. Understanding the mechanisms of Mtb virulence factors can provide new directions for targeted tuberculosis therapy. Therefore, knowledge of these virulence factors is essential for the development of new vaccines and anti-tuberculosis drugs. In this review, we summarize the latest research progress in the virulence factors of Mtb to provide a reference for targeted treatment of tuberculosis.

Objective:To investigate the clinicopathological features, immunophenotype, and gene rearrangement status of hyalinizing clear cell carcinoma (HCCC) of the salivary glands, in order to better understand this rare tumor and improve its precision diagnosis and treatment.Methods:A total of 65 cases of salivary gland HCCC diagnosed at the Peking University School and Hospital of Stomatology, Beijing, China between January 2001 and May 2024 were collected. Clinical features, pathological characteristics, EWSR1 gene rearrangement, and follow-up data were analyzed.Results:There were 33 males and 32 females. The age of the patients ranged from 22 to 85 years, with a median age of 54.0 (40.0, 63.5) years. 93.8% (61/65) of the tumors occurred in the minor salivary glands, most commonly in the palate. Microscopically, the tumors were mainly composed of clear tumor cells. Squamous differentiation was observed in 66.2% (43/65) of the tumors, and mucinous cells in 36.9% (24/65). The tumor stroma showed delicate fibrous septa or hyalinized sheets between tumor nests. Lymph node metastasis occurred in 12.3% (8/65) of the cases, and high-grade transformation was observed in 6.2% (4/65). Tumor cells were all positive for p40 and p63, while SOX10 was positive in 12.3% (8/65) of them. Myoepithelial markers were negative. EWSR1 gene rearrangement was detected in 96.6% of the tumors. Follow-up data showed a 5-year overall survival rate of 93.8%, a local recurrence rate of 9.2%, and a distant metastasis rate of 4.6%.Conclusions:HCCC predominantly arises in minor salivary glands and generally has a favorable prognosis. However, a small proportion of the cases may show high-grade transformation, lymph node metastasis, local recurrence, or distant metastasis. It thus requires long-term and regular follow-up. Accurate diagnosis should be based on a comprehensive assessment of histopathological features, immunophenotype, and gene fusion status.

Objective:To investigate the clinicopathological features, immunophenotype, and gene rearrangement status of hyalinizing clear cell carcinoma (HCCC) of the salivary glands, in order to better understand this rare tumor and improve its precision diagnosis and treatment.Methods:A total of 65 cases of salivary gland HCCC diagnosed at the Peking University School and Hospital of Stomatology, Beijing, China between January 2001 and May 2024 were collected. Clinical features, pathological characteristics, EWSR1 gene rearrangement, and follow-up data were analyzed.Results:There were 33 males and 32 females. The age of the patients ranged from 22 to 85 years, with a median age of 54.0 (40.0, 63.5) years. 93.8% (61/65) of the tumors occurred in the minor salivary glands, most commonly in the palate. Microscopically, the tumors were mainly composed of clear tumor cells. Squamous differentiation was observed in 66.2% (43/65) of the tumors, and mucinous cells in 36.9% (24/65). The tumor stroma showed delicate fibrous septa or hyalinized sheets between tumor nests. Lymph node metastasis occurred in 12.3% (8/65) of the cases, and high-grade transformation was observed in 6.2% (4/65). Tumor cells were all positive for p40 and p63, while SOX10 was positive in 12.3% (8/65) of them. Myoepithelial markers were negative. EWSR1 gene rearrangement was detected in 96.6% of the tumors. Follow-up data showed a 5-year overall survival rate of 93.8%, a local recurrence rate of 9.2%, and a distant metastasis rate of 4.6%.Conclusions:HCCC predominantly arises in minor salivary glands and generally has a favorable prognosis. However, a small proportion of the cases may show high-grade transformation, lymph node metastasis, local recurrence, or distant metastasis. It thus requires long-term and regular follow-up. Accurate diagnosis should be based on a comprehensive assessment of histopathological features, immunophenotype, and gene fusion status.

Type 1 diabetes mellitus (T1DM)-induced cognitive dysfunction is common, but its underlying mechanisms are still poorly understood. In this study, we found that knockout of conventional protein kinase C (cPKC)γ significantly increased the phosphorylation of Tau at Ser214 and neurofibrillary tangles, but did not affect the activities of GSK-3β and PP2A in the hippocampal neurons of T1DM mice. cPKCγ deficiency significantly decreased the level of autophagy in the hippocampal neurons of T1DM mice. Activation of autophagy greatly alleviated the cognitive impairment induced by cPKCγ deficiency in T1DM mice. Moreover, cPKCγ deficiency reduced the AMPK phosphorylation levels and increased the phosphorylation levels of mTOR in vivo and in vitro. The high glucose-induced Tau phosphorylation at Ser214 was further increased by the autophagy inhibitor and was significantly decreased by an mTOR inhibitor. In conclusion, these results indicated that cPKCγ promotes autophagy through the AMPK/mTOR signaling pathway, thus reducing the level of phosphorylated Tau at Ser214 and neurofibrillary tangles.
AMP-Activated Protein Kinases/metabolism* ; Animals ; Autophagy ; Diabetes Mellitus, Type 1 ; Glucose ; Glycogen Synthase Kinase 3 beta/metabolism* ; Mice ; Phosphorylation ; Protein Kinase C/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; tau Proteins/metabolism*

Monoclonal gammopathy of neural significance (MGNS) belongs to the category of monoclonal gammopathy of clinically significance. It is an early-stage disease that mainly occurs in peripheral nerves and is not sufficient for the diagnosis of multiple myeloma or lymphoma. MGNS needs to be differentiated from neuropathies due to POEMS syndrome and light-chain amyloidosis; if necessary, nerve biopsy can be performed to clarify the relationship between peripheral nerve symptoms and lymphoplasmacytic disease. Treatment of MGNS is recommended to give intravenous gammaglobulin, plasma exchange and targeted anti-lymphoplasmacytic tumour therapy such as CD20 monoclonal antibody. Early recognition and intervention of MGNS, with multidisciplinary cooperation, will help to reduce the risk of malignancy and the incidence of disability.

Objective:To identify the risk factors for massive blood transfusion in pediatric living donor liver transplantation.Methods:The medical data of children underwent living donor liver transplantation in our hospital from April 2006 to April 2019 were retrospectively collected.Massive transfusion was defined as the administration of red blood cells > 1 fold of the total blood volume (70 ml/kg) during operation.Patients were assigned to massive transfusion group and non-massive transfusion group according to the volume of blood transfused during operation.Binary logistic regression analysis was used to identify the risk factors for massive blood transfusion during living liver transplantation.Results:A total of 95 pediatric patients were enrolled in this study, with 18 cases in massive transfusion group and 77 cases in non-massive transfusion group.The incidence of massive blood transfusion was 19% during operation.The results of logistic regression analysis showed that preoperative survival status of " hospitalization" ( OR=49.816, 95% CI 2.945-842.59, P=0.007), increased serum Cr concentrations ( OR=1.046, 95% CI 1.007-1.086, P=0.021), increased Pediatric End-Stage Liver Disease (PELD) or Model for End-Stage Liver Disease (MELD) score ( OR=1.215, 95% CI 1.046-1.411, P=0.011) and prolonged operation time( OR=1.623, 95% CI 1.133-2.327, P=0.008) were the independent risk factors for intraoperative massive blood transfusion in living donor liver transplantation, while increased recipient weight ( OR=0.856, 95% CI 0.761-0.962, P=0.009) was a protective factor for intraoperative massive blood transfusion. Conclusions:Preoperative survival status of " hospitalization", increased PELD or MELD score and prolonged operation time are independent risk factors, while increased pediatric weight is a protective factor for massive blood transfusion in pediatric living donor liver transplantation.