BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

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*

As the second largest vector of infectious diseases, ticks carry and transmit various pathogens that cause human infections and pose a serious public health hazard. In recent years, there has been an ongoing epidemic of tick-borne fever with thrombocytopenia syndrome virus (SFTSV), as well as the occurrence of human infections by brand-new viruses such as Jingmen tick virus (JMTV) and Alongshan virus (ALSV) in China. This paper will review the advancement of disease clinical characteristics, laboratory methods of virus isolation, immunology and molecular biology of these emerging tick-borne viral diseases in China.

Objective:To investigate the pathogen spectrum of acquired immunodeficiency syndrome (AIDS) patients with pulmonary opportunistic infections in the local area, and to evaluate the clinical application of metagenomic next-generation sequencing (mNGS) in these patients.Methods:From January to December 2021, AIDS patients with pulmonary infections admitted to Zhongnan Hospital of Wuhan University were enrolled. Their bronchoalveolar lavage fluid (BALF) was subjected to mNGS and coventional pathogen detection.Routine pathogen detection methods included smear, culture, polymerase chain reaction (PCR), and immunochromatographic colloidal gold. Fisher′s exact probability method was used for statistical analysis.Results:A total of 69 patients were included, and all of them were tested positive for mNGS. Among them, 53 cases (76.8%) were positive for fungi and viruses, 40 cases (58.0%) were positive for bacteria (excluding Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria (NTM)), six cases were positive for MTB, 11 cases were positive for NTM, and seven cases were positive for other pathogens. Mixed infections with two or more pathogens were found in 89.9%(62/69) of the patients. Among the conventional pathogen detections of BALF, 79.7%(55/69) of the patients were positive for pathogens, including 42 cases positive for Pneumocystis jirovecii PCR, 16 cases positive for BALF culture, nine cases positive for MTB PCR, and five cases positive for Cryptococcus antigen. The total detection rate of mNGS was 100.0%(69/69), which was higher than that of the conventional pathogen detection rate of 79.7%(55/69), and the difference was statistically significant (Fisher′s exact probability method, P<0.001). The specificity of mNGS detection was 88.4%. Combining clinical and two detection methods, the top five pathogens were Pneumocystis jirovecii (62.3%(43/69)), Candida (29.0%(20/69)), MTB (20.3%(14/69)), NTM and Talaromyces marneffei (15.9%(11/69), each). Fifty-three patients (76.8%) had co-infection with virus. Conclusions:The main cause of pulmonary infection in AIDS patients in this area is mixed infection, and Pneumocystis jirovecii is the most common pathogen. mNGS could significantly improve the pathogen detection rate in AIDS patients with pulmonary infections.

Objective:To analyze the clinical features, treatment, and outcomes of fetal/neonatal atrial flutter (AFL) at the onset of the perinatal period to improve the management of this condition.Methods:This retrospective study analyzed the clinical data, treatment, and follow-up results of fetal/neonatal AFL cases transferred to Shanghai Children's Medical Center from November 2013 to August 2021. Clinical characteristics, cardioversion procedures, and outcomes were summarized. Descriptive method was used for statistical analysis.Results:A total of 21 fetuses/neonates presenting with AFL in the perinatal period were involved in this study, including 17 males and four females. Ten of them were born at full term, and 11 were preterms. All of the patients were delivered by cesarean section at 32 to 41 gestational weeks [ (36.6±1.9) weeks] with a birth weight of 2 130 to 4 450g [ (3 059±528) g]. Increased fetal heart rate was all detected after 32 weeks of gestation, and three of them were diagnosed with AFL by fetal echocardiography before being born. The heart rate remained elevated in all cases after birth. All were diagnosed as AFL based on an electrocardiogram on the day of birth, which showed a 2 to 6 over one ratio of atrioventricular conduction. Among the six cases of cardiac insufficiency and low blood pressure complicated by dyspnea and cyanosis, the symptoms were relieved in four cases after mask oxygenation and two cases after ventilation. Among the 21 cases, one was converted spontaneously to normal sinus rhythm and the other 20 recovered after medication or electrical cardioversion. Seven cases were initially treated by drug conversion with a success rate of 5/7 and hospitalized for 23 d (13-25 d). There was one with cardiac insufficiency before treatment and three newly developed cardiac insufficiency during treatment among the seven cases. Thirteen cases were offered electrical cardioversion initially, and the success rate of cardioversion was 12/13. There were five cases of cardiac insufficiency before treatment, while no new cases of cardiac insufficiency was reported during treatment. The duration of hospitalization was 11 d (9-14 d). Apart from one case, the rest 20 infants were followed up from one month to eight years old, and no recurrence was reported.Conclusions:For fetal/neonatal AFL with the onset during the perinatal period, the symptoms mainly manifest in late pregnancy. Its diagnosis depends on fetal echocardiography before birth or electrocardiogram after birth, and electrical cardioversion is a fast and effective measure. While the prognosis of perinatal-onset AFL is generally good.

Background Front-line medical staff are an important group in fighting against Coronavirus Disease 2019 (COVID-19), and their mental health should not be ignored. Objective This study investigates the current situation and influencing factors of post-traumatic stress disorder (PTSD) among front-line anti-epidemic medical staff during COVID-19 epidemic. Methods Medical staff who had participated in fighting against the COVID-19 epidemic wereselected from three grade III Class A hospitals and four grade II Class A hospitals in a city of Hubei Province by convenient sampling method in May 2020. The survey was conducted online using the Post-traumatic Stress Checklist-Civilian Version (PCL-C) as the main survey tool to investigate current situation and characteristics of PTSD among these participants. A total of 1120 questionnaires were collected, of which 1071 were valid, and the effective rate was 95.6%. Results Of the 1071 participants, the average age was (32.59±5.21) years; the ratio of male to female was 1: 5.02; the ratio of doctor to nurse was 1:5.8; nearly 70% participants came from grade III Class A hospitals; married participants accounted for 75.4%; most of them held a bachelor degree or above (86.5%); members of the Communist Party of China (CPC) accounted for 22.9%; 50.9% had junior titles; the working years were mainly 5−10 years (42.8%); more than 80.0% participants volunteered to join the front-line fight; 95.1% participants received family support; 43.0% participated in rescue missions; 78.1% participants fought the epidemic in their own hospitals; more than 60% participants considered the workload was greater than before; 34.4% participants fought in the front-line for 2−4 weeks, and 23.5% participants did for more than 6 weeks. There were 111 cases of positive PTSD syndromes (PCL-C total score ≥38) with an overall positive rate of 10.4%, and the scores of reexperience [1.40 (1.00, 1.80)] and hypervigilance [1.40 (1.00, 2.00)] were higher than the score of avoidance [1.14 (1.00, 2.57)]. The results of univariate analysis revealed that PTSD occurred differently among participants grouped by age, political affiliation, working years, anti-epidemic activities location, accumulated working hours in fighting against COVID-19, having child parenting duty, voluntariness, family support, whether family members participated in front-line activities, and rescue mission assignment (P<0.05). The results of logistic regression analysis showed that the incidence rates of reporting PTSD syndromes in medical personnel aged 31−40 years (OR=0.346, 95%CI: 0.164−0.730) and aged 41 years and above (OR=0.513, 95%CI: 0.319-0.823) were lower than that in those aged 20−30 years; the incidence rates of reporting PTSD syndromes in medical staff who were CPC members (OR=0.499, 95%CI: 0.274−0.909), volunteered to participate (OR=0.584, 95%CI: 0.360−0.945), and received family support (OR=0.453, 95%CI: 0.222-0.921) were lower than those did not (P<0.05); the incidence rates of reporting PTSD syndromes among medical workers who had child parenting duty (OR=2.372, 95%CI: 1.392−4.042), whose family members participated in front-line activities (OR=1.709, 95%CI: 1.135−2.575), and who participated in rescue missions (OR=1.705, 95%CI: 1.133-2.565) were higher than those who did not (P<0.05). Conclusion The positive PTSD syndrome rate is 10.4% in the front-line anti-epidemic medical staff. Age, political affiliation, voluntariness, family support, having child parenting duty, with a family members participating in the fight, and rescue mission assignment are the influencing factors of PTSD.

Objective:To investigate the clinicopathological features of hepatic vascular tumors in children. Methods The clinical characteristics, histology and immunohistochemical staining results were summarized and analyzed in 22 cases of hepatic vascular tumors in children at Guangzhou Women and Children′s Medical Center from September 2007 to November 2020. Results:The 22 patients aged from 1.0 month to 2.5 years (mean age 9 months). There were 10 males and 12 females. Five cases were found in premature and had low birth weight infants; three cases were discovered in the antenatal period; one patient also had cutanous hemangioma; six patients had associated anemia; Kasabach-Merritt phenomenon was not seen in any patient. CT examination showed 17 tumors were solitary and five were multifocal lesions. Macroscopically, the tumors size ranged from was 0.6 cm to 11.0 cm; the cut surface was solid, gray red and brown in color, and in six cases there were hemorrhage and necrosis in the central area. Microscopically,15 cases of solitary congenital hepatic hemangiomas showed characteristic necrosis in the central area, with loose fibrous tissues at periphery. Proliferation of capillaries, residual bile ducts between the vascular lumens, and dilated thrombosed vascular channels were seen, and contained extramedullary hematopoietic foci and calcification. Five cases of multiple hepatic infantile hemangiomas showed capillaries of different sizes composing of plump endothelium and pericytes and were arranged in lobular or diffuse patterns. Two cases of cavernous hemangioma (venous malformation) consisted of dilated thin-walled blood vessels with branch-like pattern lined with flat endothelial cells. Immunohistochemically, all 22 case expressed vascular endothelial markers CD31 and CD34, but D2-40 was negative. Glut1 was positive in five cases of multiple hepatic infantile hemangiomas, and the other cases were negative.Conclusion:Hepatic vascular tumors in children are rare, and their classification is different from that of adults. It is of great significance to make clear pathologic diagnosis.

Objective:To explore the epidemiological characteristics, clinical characteristics, treatment strategies and clinical results of non-dislocated hyperextension tibial plateau fracture.Methods:A total of 25 cases of non-dislocated hyperextension tibial plateau fracture patients were collected, including 12 males and 13 females, aged 27-79 years with an average age of 51±15 years. Causes of injury: 18 cases of traffic accident, 2 cases of heavy injury, 5 cases of falling injury. Schatzker classification of tibial plateau fracture: 4 cases of type II, 5 cases of type IV, 13 cases of type V, 3 cases of type VI. Three columns theoretical classification: 4 cases of simple lateral column, 5 cases of simple medial column, 7 cases of medial column+lateral columns, 9 cases of three columns. Preoperative tibial plateau posterior slope angle was -10-0 degrees, average-5.2 degrees. Preoperative MRI showed 5 cases of medial collateral ligament (MCL) injury, 3 cases of posterolateral complex (PLC) complex injury, 2 cases of PLC+ posterior cruciate ligament (PCL) injury and 10 cases of menisci injury. The change of tibial plateau posterior slope angle was more than 10 degrees in patients with ligament injury, 5 patients had a tibial plateau posterior slope angle change more than 15 degrees, 5 patients had a tibial plateau posterior slope angle change more than 10 degrees, and the patients with a tibial plateau posterior slope angle change less than 10 degrees had no ligament injury; 6 patients with simple lateral column or medial column fracture had a ligament injury, 2 patients with medial column+lateral column fracture had a ligament injury, and 2 patients with three column fracture had a ligament injury.Results:All patients were followed up for 12-24 months, with an average of 16.4 months. The operation time was 124±33 min (65-180 min), and the bleeding volume was 106±48 ml (20-200 ml). All patients were treated by open reduction and internal fixation. According to the characteristics of fracture, targeted reduction of articular surface and restoration of lower limb force line were carried out. The plate was placed on the anterior part of tibial plateau to fix the fracture fragment. Evaluation of postoperative fracture reduction: 20 cases were anatomic reduction, 5 cases were good reduction (between 2-5 mm articular surface collapse), and the excellent rate of fracture reduction was 100%. Internal fixation: 4 cases were treated with simple lateral plate, 2 cases with simple medial plate, 15 cases with medial+ lateral plate, 1 case with medial plate+ lateral anchor suture, 1 case with medial plate+ posterior screw, 1 case with lateral plate+ fibular screw, 1 case with medial plate + lateral plate+ lateral anchor suture. The meniscus was repaired in 8 patients, including 5 medial and 3 laterals. The fracture healing time was 3-6 months (mean 3.3 months). The postoperative knee Rasmussen score was 24.9±3.5 (18-29), and the postoperative knee joint mobility was 118°±9° (90°-130°). Superficial infection occurred in 2 patients.Conclusion:The main imaging characteristic of "non-dislocated hyperextension tibial plateau fracture" is the change of tibial plateau posterior slope angle. The injury of single anteromedial column/anterolateral column fracture is easy to combine with the "diagonal" injury, and when the tibial plateau posterior slope angle changes more than 10 degrees, it is easy to be associated with peripheral ligament injury. By using open reduction and internal fixation, restoring the joint articular surface and lower limb force line, repairing the soft tissue structure and ligament, and reconstructing the stability of knee joint, we can achieve satisfactory results.

In December 2019, a cluster of patients with pneumonia of unknown cause were linked to a seafood wholesale market in Wuhan, China. Some studies found that the virus was a new kind of virus which had never been found in the human body. Then, the virus was named 2019 Novel Coronavirus (2019-nCoV) by the World Health Organization (WHO). 2019-nCoV nucleic acid detection is one of the essential indicators of NCP (Novel Coronavirus Pneumonia). Recently, some false-negative cases in China-Japan Friendship Hospital and Hangzhou Hospital led the clinical doctors to question the value of the nucleic acid detection. In this paper, more than 3 000 results of 2019-nCoV detection in Zhongnan Hospital, Wuhan University were analyzed. Attention should be paid to the root cause of false-negative results and the related countermeasures should be taken.

In December 2019, a cluster of patients with pneumonia of unknown cause were linked to a seafood wholesale market in Wuhan, China. Some studies found that the virus was a new kind of virus which had never been found in the human body. Then, the virus was named 2019 novel coronavirus (2019-nCoV) by the World Health Organization (WHO). 2019-nCoV nucleic acid detection is one of the essential indicators of COVID-19. Recently, some false-negative cases in China-Japan Friendship Hospital and Hangzhou Hospital led the clinical doctors to question the value of the nucleic acid detection. In this paper, more than 3 000 results of 2019-nCoV detection in Zhongnan Hospital, Wuhan University were analyzed. Attention should be paid to the root cause of false-negative results and the related countermeasures should be taken.