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*

Objective:To investigate the relationship between the changes of electrocardiogram QRS duration features and the occurrence of adverse cardiac events in patients with heart failure.Methods:The clinical data of 298 patients with heart failure who received treatment in Lishui City People's Hospital from June 2021 to June 2022 were retrospectively analyzed. According to the type of heart failure, they were divided into the diastolic heart failure group ( n = 158) and the systolic heart failure group ( n= 140). According to whether having cardiac events, they were divided into a cardiac event group ( n = 97) and a non-cardiac event group ( n = 201) group. An additional 120 patients who concurrently received health examinations were included in the control group. QRS wave duration and cardiac function indicators were analyzed. QRS wave duration and cardiac function indicators were compared between heart failure and control groups. Changes in QRS wave duration and cardiac function indicators were compared between diastolic heart failure and systolic heart failure groups. Changes in QRS wave duration and cardiac function indicators were compared between cardiac event and non-cardiac event groups. The value of the receiver operating characteristic curve in predicting adverse cardiac events was analyzed. Pearson correlation analysis was performed to analyze the correlation between QRS wave duration and cardiac function. Results:QRS wave duration in the heart failure group was (125.42 ± 14.35) ms, which was significantly longer than (78.82 ± 6.49) ms in the control group ( t = 34.17, P < 0.001). Left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV) in the heart failure group were (156.24 ± 21.42) mL and (78.28 ± 9.43) mL, respectively, which were significantly higher than (107.48 ± 19.23) mL and (45.62 ± 5.42) mL, respectively in the control group ( t = 21.66, 35.63, both P < 0.01). Left ventricular ejection fraction (LVEF) in the heart failure group was (46.98 ± 4.25)%, which was significantly lower than (67.94 ± 5.46)% in the control group ( t = 41.88, P < 0.001). QRS wave duration in the systolic heart failure group was (140.21 ± 18.57) ms, which was significantly longer than (112.31 ± 13.42) ms in the diastolic heart failure group ( t = 16.29, P < 0.001). LVESV and LVEDV in the systolic heart failure group were (183.36 ± 27.67) mL and (95.39 ± 12.13) mL, respectively, which were significantly higher than (132.21 ± 18.98) mL and (63.12 ± 7.84) mL in the diastolic heart failure group ( t = 20.30, 29.61, both P < 0.001). LVEF in the systolic heart failure group was (38.19 ± 4.61)%, which was significantly lower than (54.77 ± 4.92)% in the diastolic heart failure group ( t = 34.18, P < 0.001). QRS wave duration in the cardiac event group was (169.37 ± 17.43) ms, which was significantly longer than (104.21 ± 12.49) ms in the non-cardiac event group ( t = 36.91, P < 0.001). LVESV and LVEDV in the cardiac event group were (199.30 ± 23.41) mL and (105.22 ± 15.64) mL, respectively which were significantly higher than (135.46 ± 15.46) mL and (65.28 ± 6.92) mL in the non-cardiac event group ( t = 28.04, 30.57, both P < 0.001). LVEF in the cardiac event group was (32.97 ± 5.16)%, which was significantly lower than (53.74 ± 4.52)% in the non-cardiac event group ( t = 35.46, P < 0.001). The receiver operating characteristic curve analysis showed that the sensitivity and specificity of QRS wave duration in predicting adverse cardiac events were 88.7% and 86.6%, respectively. Pearson analysis showed that QRS wave duration, LVESV, and LVEDV were positively correlated with the occurrence of adverse cardiac events ( r = 0.684, 0.546, 0.518, all P < 0.05), while LVEF was negatively correlated with the occurrence of adverse cardiac events ( r = -0.627, P < 0.05). Conclusion:QRS wave duration in patients with heart failure is significantly prolonged, and it is obviously related to the occurrence of adverse cardiac events.

OBJECTIVES: This study aimed to clarify the effects of Foxp3 silencing on the expression of inflammatory cytokines in human periodontal ligament cells (hPDLFs) in an inflammatory environment and on cell proliferation and invasiveness, as well as to explore the role of Foxp3 gene in the development of periodontitis. METHODS: An small interfering RNA (siRNA) construct specific for Foxp3 was transfected into hPDLFs. Foxp3 silencing efficiency was verified by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, and the siRNA with the optimum silencing effect of Foxp3 gene was screened. Using lipopolysaccharide to simulate an inflammatory environment in vitro, CCK-8 detected the effect of silencing Foxp3 on hPDLFs proliferation under inflammatory conditions. Wound-healing experiments and transwell assays were conducted to detect the effect of silencing Foxp3 on hPDLF migration under inflammatory conditions. The expression of the inflammatory cytokines interleukin (IL)-6 and IL-8 was detected by RT-PCR and Western blotting under inflammatory conditions. RESULTS: After siRNA transfection, RT-PCR and Western blotting analyses showed that the expression of Foxp3 mRNA in the Foxp3-si3 group decreased significantly (t=21.03, P<0.000 1), and the protein expression of Foxp3 also decreased significantly (t=12.8, P<0.001). In the inflammatory environment, Foxp3 gene silencing had no significant effect on hPDLFs proliferation (P>0.05), and Foxp3 gene silencing promoted hPDLFs migration (P<0.05). Moreover, the expression of IL-6 and IL-8 increased (P<0.05). CONCLUSIONS In an inflammatory environment, Foxp3 gene silencing promoted hPDLFs migration but had no significant effect on hPDLFs proliferation. The expression of inflammatory factors expressed in hPDLFs increased after Foxp3 gene silencing, indicating that Foxp3 gene inhibited inflammation in periodontitis.
Humans ; Cell Proliferation/genetics* ; Cells, Cultured ; Cytokines/metabolism* ; Fibroblasts/metabolism* ; Forkhead Transcription Factors/metabolism* ; Gene Silencing ; Interleukin-6/metabolism* ; Interleukin-8/metabolism* ; Periodontal Ligament/metabolism* ; Periodontitis/metabolism* ; RNA, Small Interfering/metabolism* ; Transcription Factors/metabolism*

Comprehensive experiments course is a bridge for higher vocational students to integrate theoretical knowledge with production practice. The article introduces that our biological pharmacy department is committed to the principles of "promotion of teaching, learning and construction through skills competition so as to integrate education and training". By taking penicillin fermentation process as an example, reform has been made in several aspects including teaching objectives, teaching content and teaching methods. We integrate the practical operation of fermentation equipment with virtual simulation software to develop a two-way interactive course. By reducing the subjective dependence, the quantitative management and evaluation of fermentation process parameter control were put into place, which efficiently integrated the skills competition with practical teaching. Improved teaching performance has been achieved over recent years, which may facilitate the reform and practice of similar courses based on skills competition.
Humans ; Clinical Competence ; Learning ; Students ; Technology ; Biological Products

Objective:To explore the molecular biological effects of Zu-san-li in the treatment of diseases. Methods:Literatures in CNKI, Wan-fang and VIP databases on acupuncture and moxibustion treatment of diseases from January 1, 1999 to April 30, 2019 were retrieved, and the target of Zu-san-li for treating diseases were obtained. The disease enrichment, GO bioprocess enrichment and KEGG pathway enrichment were performed on these targets. Results:A total of 297 articles were included, involving 196 targets. Six diseases, mainly including tumors, nervous system, cardiovascular system, digestive system and other diseases, 18 GO bioprocess related items and 10 signaling pathways, involving signaling pathways such as immunity, cytokines, and gastrin secretion, what those were enriched.Conclusions:Acupuncture at Zu-san-li can treat diseases of multiple systems, which is related to its multi-target and multi-path mechanism. The study can provide a basis for further elucidating the mechanism of action of acupuncture treatment.

Objective To investigate the clinical value of three-dimensional sampling perfection with application optimized contrasts using different flip angle evolutions (3D-SPACE) sequence in preoperative evaluation of acoustic neuroma.Methods Totally 57 patients with acoustic neuroma confirmed by surgery and pathology were enrolled.All patients underwent preoperative routine head MR and 3D-SPACE sequence.The position,size and shape of the tumors were observed,and the display rate of surrounding cranial nerves was evaluated with 3D-SPACE sequence.The results were compared with those of conventional MRI and operation.Results All 57 patients were found with single tumor.The tumor in 1 patient (1/57,1.75％) limited in the internal auditory canal,and those in another 56 patients (56/57,98.25％) exceed the internal auditory canal crossing growth.The inner auditory canal fundus in 26 patients (26/57,45.61 ％) were completely filled by the tumors,while those in another 31 patients (31/57) were uncompletely filled.3D-SPACE sequence showed 21 patients (21/57,36.84％) with solid type lesions,35 patients (61.40％,35/57) with solid with cystic type lesions and 1 patient (1/57,1.76％) with cystic type lesion.The coincidence rate of lesion types showed with 3D-SPACE sequence and intraoperative findings was 85.96 ％ (49/57).The display rate of trigeminal nerve internal cisternal segment,lower cranial nerves cisternal segment,abducens nerve cisternal segment,facial nerve internal acoustic meatus segment,facial nerve cisternal segment and acoustic nerve cisternal segment was 100％ (57/57),100％(57/57),75.44％ (43/57),50.88％ (29/57),17.53％ (10/57) and 19.30％ (11/57),respectively,all significantly increased compared with those of conventional MRI (all P＜0.05).Conclusion 3D-SPACE sequence can accurately display the relationship between tumor and adjacent cranial nerves,therefore has important clinical value in preoperative evaluation of acoustic neuroma.

Objective To explore the value of small surface coil combined with three-dimensional double-echo steady-state with water excitation (3D-DESS-WE) sequence in displaying mandibular nerves and their branches. Methods The maxillofacial regions of 52 volunteers were scanned unilaterally by a small surface coil combined with 3D-DESS-WE sequence. According to the Gray's anatomy atlas,MPR and CPR was done according to the anatomic position of mandibular nerve and the branches,the signal characteristics of the nerves and neighboring structures were analyzed. The displaying rate of the mandibular nerves and their branches were evaluated.The image quality and display of the nerve were subjectively scored. The signal intensity(SI) of the nerve and adjacent lateral pterygoid muscle were measured. The signal intensity ratio(SIR) of mandibular nerve/lateral pterygoid muscle (SIRN/M) was calculated. Results Compared with the muscles, the nerve showed iso-signal intensity. The subjective scores for all small coil 3D-DESS-WE images were 3.02 ± 0.82. The displaying rates of V3 trunk,anterior trunk,buccal nerve, posterior trunk,inferior alveolar nerve and lingual nerve were all 100%. V3 posterior trunk,inferior alveolar nerve and lingual nerve showed the best quality scores,which were all about 3 points,and the SIRN/M were about 1. The auricular temporal nerve and masseter muscle nerve were also basically satisfied. The displaying rate of mylohyoid muscle nerve,medial pterygoid nerve and lateral pterygoid nerve was low. Conclusion Small surface coil combine with 3D-DESS-WE sequence performed high-quality in mandibular nerves and their branches MR imaging using MPR,CPR post-processing technology,which are suitable for clinical application.

Objective To explore the application value of circulating tumor cell (CTC) counting in the diagnosis of patients with colorectal cancer.Methods From July to October in 2015,a total of 61 patients firstly diagnosed with colorectal cancer,at stagc] to Ⅳ were enrolled.At the same period,20 individuals (healthy volunteers or patients with benign colorectal diseases) were selected as controls.Peripheral blood (7.5 mL) was taken before therapy.Peripheral blood CTC were counted by immunomagnetic beads enrichment combined with fluorescent staining method in two hours.The positive detection rate of CTC for colorectal cancer,especially early colorectal cancer was analyzed.And the priority of combination it with carcino-embryonic antigen (CEA) was also investigated.Chi-square test,t test and rank-sum test were used for statistical analysis.Results Two patients could not be pathological staged,due to the lack of whole body imaging evaluation.There were 30 patients with colorectal cancer at early stage (stage Ⅰ to Ⅱ) and 29 patients at advanced stage (stage Ⅲ to Ⅳ).The difference in CEA level between patients at early stage and advanced stage ((3.3±1.1) μg/L vs (20.4±3.3) μg/L) was statistically significant (t=-2.74,P=0.008).The median cell number of CTC of colorectal cancer group and control group was 1 (interquartile range=4) and 0,respectively,and the difference was statistically significant (Z=2.721,P=0.007).Taken 0/7.5 mL and 5 μg/L as the cut-off value of CTC and CEA,the detection rates of CTC for colorectal cancer and early colorectal cancer were 65.6％ (40/61) and 63.3％ (19/30),respectively;the detection rates of CEA for colorectal cancer and early colorectal cancer were 29.5 ％ (18/61) and 13.3％ (4/30).When CTC combined with CEA,the detection rates for colorectal cancer and early colorectal cancer were 73.8％ (45/61) and 66.7％ (20/30),respectively.Conclusions CTC has certain detection value in colorectal cancer especially early colorectal cancer.If it combined with CEA,the detection rate is much higher.

Objective To understand hand hygiene(HH) compliance among health care workers(HCWs) and incidence of healthcare-associated infection(HAI) in surgical patients before and after the intervention, analyze the effect of HH on cost-effectiveness of HAI.Methods From December 2012-June 2014, 78 HCWs in the department of neurosurgery of a hospital were as the intervention objects of HH compliance, 325 patients who underwent craniocerebral clean operation were as the surveyed objects, HH compliance among HCWs, incidence of HAI in surgical patients, cost of HH, and hospitalization expense before and after intervention were compared respectively.Results HH compliance among HCWs before and after intervention were 35.24% (216/613) and 73.75%(486/659)respectively (X2=180.091,P<0.001);incidence of HAI in surgical patients before and after intervention were 31.85%(50/157)and 18.45%(31/168)respectively(X2=7.782,P<0.001).Hospitalization expense before and after intervention were (89 524.90±38 856.70)￥ and (61 401.00±29 237.80)￥ respectively;average length of hospital stay before and after intervention were 36.70 days and 26.90 days respectively(t=3.296, 3.511,respectively, both P<0.01).Conclusion Improving HH compliance among HCWs can reduce the incidence of HAI and hospitalization cost, and shorten the average length of hospital stay of patients.