Objective: To investigate the characteristics and risk factors of an outbreak of acute hemorrhagic conjunctivitis (AHC) in a boarding middle school in Guangdong Province, in order to provide a scientific evidence for effective prevention and control of campus AHC outbreaks. Methods: From September 1st to 28th 2023, case identification was conducted among 559 students and 60 faculty members using standardized definition. Descriptive analysis was conducted on the three distrubution patterns of the outbreak. Questionnaires were designed, and a case-control study was adopted to analyze the possible risk factors of the disease transmission. The propensity score matching (PSM) method was used to control the difference of baseline data. Results: A total of 269 cases of AHC were identified, with an attack rate of 43.46%. The pathogen was confirmed as Coxsackie virus A24 variant (CA24v). Among these, 264 cases were students (attack rate of 47.23%) and 5 were staff (attack rate of 8.33%). A total of 153 pairs of PSM were successfully matched. After PSM matching, there were no statistically significant differences in gender, grade and class between the case group and the control group ( χ 2=0.12, 5.41, 11.24, P >0.05). The results of multivariate Logistic regression analysis showed that middle school students whose towels contacted with others ( OR =1.81), and direct contact with other AHC cases recently ( OR =4.89) were more likely to have AHC; while wearing glasses ( OR =0.43) and frequent use of hand sanitizer ( OR = 0.37 ) were less likely to have AHC ( P <0.05). Conclusion The outbreak of AHC is caused by CA24v, demonstrating rapid spread and extensive impact within the school setting.

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

As a traditional Chinese medicine (TCM), borneol has shown superior ability for anti-inflammatory and analgesic activities when coupled with other active ingredients from ancient times. Furthermore, borneol is believed to improve blood concentration and bioavailability of drugs. Thus, it has been paired with various TCM formulas since ancient time. The physiological barriers in human can cause significant limitations in drug efficiency as the drug is primarily restricted from entering into blood and brain. Borneol has been proven to enhance the permeability of biological barriers such as the blood-brain, transdermal, corneal, and intestinal barriers. Moreover, growing interest has been shown in the drug delivery system design for trans-barrier transport involving borneol. Nano-drug delivery system with increased surface area and improved active sites, has been applied to increase the bioactivity of water insoluble drugs. Nano-drug delivery system has been used to enhance drug efficacy by reducing the time of action as compared to conventional administration approach of TCM formulas. Given its ability to enhance cross-barrier permeation and drug efficacy, borneol has been integrated into TCM formulas of drug delivery system for precise and prolonged targeting at tumor sites. However, the design and preparation of a drug delivery system consisting of borneol still face great challenges. Current research fails to unravel the difference in mechanism of action between nano-drug delivery systems comprised of borneol and conventional drug systems coupled with borneol. Enhanced penetration of borneol in drug delivery system is rarely verified compared to conventional administration with identical drug formulation consisting of borneol regarding dosage and medical indications. This study outlines the current state of research on the properties, formulation and pharmacological effects of borneol, allowing cross-comparison of borneol coupled with single compound and classical TCM formulas for various medical indications. This study aims to provide insights into the design of borneol-based enhanced cross-barrier delivery drug formulation, and the potential development of nano-drug system for TCM formulas with borneol for enhanced bioavailability.

Objective To explore the dynamics of carers'caregiving dilemmas during different stages of disease progression in patients with diabetic foot ulcers,and to provide a basis for giving precise intervention strategies.Methods Based on the theory of Timing It Right,the phenomenological study was adopted.A purposive sampling method was used to select carers of patients with diabetic foot ulcers who were hospitalised in the Wound Repair Unit of a tertiary hospital in Beijing from March 2023 to February 2024 to conduct semi-structured interviews,and the data were analysed using the Colaizzi 7-step analysis method.Results Combined with the theory of Timing It Right,5 stages of diabetic foot ulcer development were formed,and 5 themes were extracted(①diagnostic period:mixed emotions,facing the dilemma of being unable to do anything;②therapeutic period:lack of knowledge of the disease,and the difficulties of bedside care;③recovery period:contradictions of the desire for rapid healing and the lack of caregiving ability;④transition period:poor patient adherence,and the hope for professional support;⑤adaptation period:the accumulation of negative emotions,and the persistence of caregiving difficulties),and 12 sub-themes.Conclusion At different stages of disease development in patients with diabetic foot ulcers,the caregiving dilemma of caregivers changes dynamically,and healthcare professionals should provide professional,personalised,and high-quality professional support according to their caregiving experience and needs at different stages to improve their quality of care and promote patients'recovery.

Objective:To investigate the clinical characteristics, diagnosis, treatment, and prognosis of primary thyroid lymphoma (PTL) .Methods:A retrospective analysis was conducted on the clinical and pathological data of 34 newly diagnosed PTL patients admitted to Beijing Tongren Hospital from September 2010 to February 2023. The Kaplan-Meier survival curve and Log-rank test were used for survival analysis, and the Cox regression model was applied for univariate analysis of prognostic factors.Results:All 34 PTL patients presented with cervical mass as the initial clinical manifestation. There were 9 males and 25 females. The pathological diagnosis was diffuse large B-cell lymphoma (DLBCL) in 29 patients and mucosa-associated lymphoid tissue (MALT) lymphoma in 5 patients. Among the DLBCL patients, 6 had B symptoms, 17 had an Eastern Cooperative Oncology Group (ECOG) score of ≥2, the Ann Arbor staging was stage Ⅰ-Ⅱ in 21 cases and stage Ⅲ-Ⅳ in 8 cases, the tumor diameter was ≥10 cm in 4 cases, and 14 had concurrent Hashimoto thyroiditis; 27 cases received chemotherapy, with 21 cases achieving complete remission (CR), 2 cases partial remission (PR), and 6 cases of disease progression; the 5-year progression-free survival and overall survival rates were 78.9% and 77.4%, respectively; univariate survival analysis showed that B symptoms, tumor diameter ≥10 cm, and Ann Arbor stage Ⅲ-Ⅳ were significant factors affecting patient prognosis ( P<0.05). MALT lymphoma patients were all in stages Ⅰ-Ⅱ, had an ECOG score of 0-1, and were without B symptoms. All patients underwent surgical resection, with 4 cases achieving CR and 1 case PR. Conclusion:PTL is more common in females with concurrent Hashimoto thyroiditis, with the majority of pathological types being B-cell lymphoma. The main treatment is chemotherapy, supplemented by radiotherapy and surgery, and the prognosis is relatively favorable.

The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK^6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK^6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK^6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK^6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK^6/7 in cells. These results suggested that FAK^6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.
Female ; Humans ; Alternative Splicing ; Breast Neoplasms/metabolism* ; Carcinoma, Pancreatic Ductal/pathology* ; Focal Adhesion Protein-Tyrosine Kinases/therapeutic use* ; Nerve Tissue Proteins/genetics* ; Neuroendocrine Tumors/genetics* ; Oncogenes ; Pancreatic Neoplasms/metabolism*

The aims of tooth restoration of endodontically treated teeth are to protect the remaining dental tissue; restore coronal morphology, functions and aesthetics; prevent bacterial microleakage and ensure periodontal healthy; prevent fracture of the restorations and reduce the wear from antagonist teeth. This article reviews the preservation and minimally invasive restoration of endodontically treated teeth. The results of the literature review show that tooth fracture resistance decreases after root canal treatment, the amount of remaining tooth tissue is an important factor affecting the success of root canal treatment, and the neck is the stress concentration area of tooth tissue, the traditional full crown and postcore crown have a certain amount of abrasion on the healthy neck teeth tissue, which will further reduce the bending resistance of the teeth and may cause the teeth to fracture. With the development of bonding technology, composite resin materials and ceramic materials, there are fewer molar tissues removed when resin, inlay, onlay, overlay and inlay crown are used to repair tooth defects, which can better preserve the remaining tooth tissues, especially the neck tooth tissues. After root canal treatment, only the pulp cavity of the tooth can be directly repaired by resin. When the marginal ridge is absent, minimally invasive restoration methods, such as inlay, onlay, and inlay crown, can be selected according to the number of marginal ridges removed and the thickness of the remaining dental tissue.

OBJECTIVETo detect mutation of adenosine deaminase acting on RNA1 (ADAR1) gene in a pedigree affected with dyschromatosis symmetrical hereditaria (DSH).

METHODSClinical data and peripheral blood samples of the patients from the pedigree were collected. Potential mutations of the ADAR1 gene were screened among 2 patients, 2 unaffected individual from the pedigree as well as 50 unrelated healthy controls by PCR amplification and direct sequencing.

RESULTSA c.3463C>T (p.R1155W) missense mutation of the ADAR gene was identified in the 2 patients, which was absent in the 2 healthy relatives and 50 unrelated controls. The mutation has been previously identified among 5 Chinese families and was the most common mutation site.

CONCLUSIONThe c.3463C>T missense mutation of the ADAR gene probably underlies the disease in this pedigree.

Objective To evaluate the effect of Aspergillus fumigatus on the expression of tumor necrosis factor-α (TNF-oα) and activation of intracellular signaling molecule p38 mitogen-activated protein kinase (p38MAPK) in a human acute monocytic leukemia cell line THP-1.Methods Cultured THP-1 cells (2 x 105/ml) were divided into 4 groups to be treated with Aspergillus fumigatus suspensions at concentrations of 106 and 107 colony-forming units (CFU)/ml (106-and 107-CFU/ml Aspergillusfumigatus groups),100 mg/L β-glucan (a positive stimulus,β-glucan group),culture medium (blank control group) respectively for 1,3 and 6 hours.Real-time fluorescence-based quantitative PCR (qPCR) was conducted to determine the mRNA expression of TNF-α in the THP-1 cells in the above groups.Some other THP-1 cells were treated with 107 CFU/ml Aspergillusfumigatus suspensions (107-CFU/ml Aspergillusfumigatus group),β-glucan (β-glucan group) and culture medium (blank control group) separately for 24 hours,and enzymelinked immunosorbent assay (ELISA) was performed to detect the level of TNF-α in the culture supernatant of THP-1 cells.Western blot analysis was conducted to detect the levels of p38MAPK and phosphorylated p38MAPK in THP-1 cells after 15-,30-and 60-minute treatment with 107 CFU/ml Aspergillusfumigatus suspensions.After 2-hour incubation with the p38MAPK inhibitor SB203580 (20 μmol/L),some THP-1 cells were additionally treated with 107 CFU/ml Aspergillus fumigatus suspensions,β-glucan and culture medium separately for 6 hours,and those without SB203580 treatment served as the control group.Then,qPCR was performed to measure the mRNA expression of TNF-α in the THP-1 cells in the above groups.Results The mRNA expression of TNF-α significantly differed among the 106-and 107-CFU/ml Aspergillus fumigatus groups,β-glucan group and blank control group (F =110.983,P ＜ 0.001),and significantly increased over time (F =701.680,P ＜ 0.001).After 24-hour treatment with 107 CFU/ml Aspergillus fumigatus suspensions,the TNF-α level(6 236.30 ± 437.12 ng/L)significantly increased compared with the blank control group (132.10 ± 0.61 ng/L,P ＜ 0.01).Thirty minutes after the treatment with 107 CFU/ml Aspergillusfumigatus suspensions,the phosphorylated p38MAPK level significantly increased,but started to decrease at 60 minutes.The mRNA expression of TNF-α was significantly lower in the SB203580-treated Aspergillusfumigatus groups (3.83 ± 0.62) than in the SB203580-untreated Aspergillus fumigatus groups (187.23 ± 21.62).Conclusion After the treatment with Aspergillus fumigatus,human THP-1 cells can activate the signal molecule p38MAPK and secrete TNF-α,suggesting that monocytes may participate in the innate immune response to Aspergillusfumigatus infection.

AIM:To investigate the roles of ClC-3 chloride channels in the regulation of cell cycle and the re-lationship between ClC-3 chloride channels and the cell cycle regulators , such as cyclin D1, cyclin-dependent kinase (CDK)4, CDK6, P21 and P27 in the HeLa cells.METHODS:ClC-3 genes were silenced by the siRNA technique in the HeLa cells.The transfection efficiency of ClC-3 siRNA was detected by real-time PCR.The cell cycle distribution was ana-lyzed by the flow cytometry .The protein expression of ClC-3, P21, P27, CDK4, CDK6 and cyclin D1 was determined by Western blot .RESULTS:ClC-3 was knocked down by ClC-3 siRNA in the HeLa cells .Transfection of the cells with ClC-3 siRNA arrested the cells at G0/G1 phases, decreased the expression of cyclin D1, CDK4 and CDK6, and increased the expression of P21 and P27.CONCLUSION:ClC-3 plays an important role in the cell cycle of HeLa cells through the G 1-S transition point.ClC-3 may regulate the cell cycle progression by up-regulation of cyclin D1, CDK4 and CDK6 expression and/or by down-regulation of P21 and P27 expression.