BACKGROUND: Senescent human skin primary fibroblast (FB) models have been established for studying aging-related, proliferative, and inflammatory skin diseases. The aim of this study was to compare the transcriptome characteristics of human primary dermal FBs from children and the elderly with four senescence models. METHODS: Human skin primary FBs were obtained from healthy children (FB-C) and elderly donors (FB-E). Senescence models were generated by ultraviolet B irradiation (FB-UVB), D-galactose stimulation (FB-D-gal), atazanavir treatment (FB-ATV), and replication exhaustion induction (FB-P30). Flow cytometry, immunofluorescence staining, real-time quantitative polymerase chain reaction, co-culturing with immune cells, and bulk RNA sequencing were used for systematic comparisons of the models. RESULTS: In comparison with FB-C, FB-E showed elevated expression of senescence-related genes related to the skin barrier and extracellular matrix, proinflammatory factors, chemokines, oxidative stress, and complement factors. In comparison with FB-E, FB-UVB and FB-ATV showed higher levels of senescence and expression of the genes related to the senescence-associated secretory phenotype (SASP), and their shaped immune microenvironment highly facilitated the activation of downstream immune cells, including T cells, macrophages, and natural killer cells. FB-P30 was most similar to FB-E in terms of general transcriptome features, such as FB migration and proliferation, and aging-related characteristics. FB-D-gal showed the lowest expression levels of senescence-related genes. In comparisons with the single-cell RNA sequencing results, FB-E showed almost complete simulation of the transcriptional spectrum of FBs in elderly patients with atopic dermatitis, followed by FB-P30 and FB-UVB. FB-E and FB-P30 showed higher similarity with the FBs in keloids. CONCLUSIONS Each senescent FB model exhibited different characteristics. In addition to showing upregulated expression of natural senescence features, FB-UVB and FB-ATV showed high expression levels of senescence-related genes, including those involved in the SASP, and FB-P30 showed the greatest similarity with FB-E. However, D-galactose-stimulated FBs did not clearly present aging characteristics.
Humans ; Fibroblasts/drug effects* ; Cellular Senescence/physiology* ; Skin/metabolism* ; Child ; Transcriptome/genetics* ; Aged ; Ultraviolet Rays ; Cells, Cultured ; Galactose/pharmacology*

IgA nephropathy (IgAN) is a glomerulonephritis characterized by diffuse deposition of immune complexes mainly composed of IgA in the mesangial area of the glomerulus. However, some patients show monotypic IgA deposits in the immunofluorescence examination, and its clinicopathological significance is not yet clear. The renal pathological changes of IgAN with monotypic IgA deposition are similar to those of proliferative glomerulonephritis with monoclonal IgA deposit (IgA-PGNMID), which has a risk of progressing to hematological malignancies and a worse clinical prognosis. It is necessary to differentiate them based on clinical pathological manifestations and hematological examinations. Based on previous literature reports and the research results of our research group, this review summarizes and analyzes the mechanism, clinical and pathological characteristics, and prognosis of IgAN with monotypic IgA deposition, and the relationship between IgAN with monotypic IgA deposition and IgA-PGNMID, to improve clinical doctors' understanding of IgAN with monotypic IgA deposition, reduce missed diagnosis and misdiagnosis, and improve patients' prognosis.

Objective: To explore the impact of personalized early treatment appliances (ETA) on the relationship between dental and maxillofacial structures in patients with ClassⅡ malocclusion during the replacement phase, and to provide a basis for clinical treatment. Methods: This study was reviewed and approved by the Medical Ethics Committee, and informed consent was obtained from patients. From May 2023 to December 2023, 15 patients with Angle ClassⅡ malocclusion accompanied by mandibular retraction and anterior deep overjet during mixed dentition were enrolled in this study (8 males and 7 females; mean age 8.8 years). Each patient received a customized domestically manufactured ETA that was created based on dental arch dimensions, overjet severity, and occlusal relationships assessed from study models. Patients were instructed to wear the appliance for at least 2 hours during the day and throughout the night. The treatment duration was 6 months, at which time the changes in cephalometric data before treatment (T0) and after treatment (T1) were compared using Uceph software Results: The angle between sella, nasion and supramentale point B (SNB) of the patients increased significantly by (1.03 ± 1.74°) compared to before treatment (P = 0.039). The angle between subspinale point A and supramentale point B (ANB), the distance between point A and point B on the FH plane (wits value), the overjet, and the overbite decreased by (0.47 ± 0.61°), (2.48 ± 2.11) mm, (2.48 ± 3.42) mm, and (0.79 ± 1.40) mm, respectively, compared to before treatment, and the differences were statistically significant (P<0.05). The angle between sella, nasion and subspinale point A (SNA), the angle between the FH and MP planes (FMA), the angle between the long axis of the L1 and MP plane (IMPA), the angle between the MP plane and SN plane (MP-SN), the distance from S to Go divided by the distance from N to Me (S-Go/N-Me), and the distance of the FH plane perpendicular from G point to the Pog point (G Vert Pog) increased compared to before treatment, while the angle between the SGn and FH planes (Y-axis) and the angle between the long axis of the L1 and FH plane (FMIA) decreased compared to before treatment, but there was no statistical difference (P>0.05). Conclusion Personalized, customized ETA orthodontic appliances can effectively improve the sagittal and vertical relationships between the maxilla and mandible in patients with ClassⅡ malocclusion.

PURPOSE: Traumatic brain injury (TBI) is a significant public health issue that impacts individuals all over the world and is one of the main causes of mortality and morbidity. Decompressive craniectomy is the usual course of treatment. Basal cisternostomy has been shown to be highly effective as an alternative procedure to decompressive craniectomy. METHODS: We conducted a retrospective cohort of patients who received surgery for severe TBI between January 2019 and March 2023. Inclusion criterias were patients between the ages of 18 and 70 years who met the diagnostic criteria for severe TBI at first presentation and who underwent surgical intervention. The exclusion criteria were patients who have severe multiple injuries at the time of admission; preoperative intracranial pressure > 60 mmHg; cognitive impairment before the onset of the disease; hematologic disorders; or impaired functioning of the heart, liver, kidneys, or other visceral organs. Depending on the surgical approach, the patients were categorized into decompressive craniectomy group as well as basal cisternostomy group. General data and postoperative indicators, including Glasgow coma scale, intracranial pressure, etc., were recorded for both groups of patients. Among them, the Glasgow outcome scale extended assessment at 6 months served as the primary outcome. After that, the data were statistically analyzed using SPSS software. RESULTS: The trial enrolled 41 patients (32 men and 9 women) who met the inclusion criteria. Among them, 25 patients received decompressive decompressive craniectomy, and 16 patients received basal cisternostomy. Three days postoperative intracranial pressure levels were 10.07 ± 2.94 mmHg and 17.15 ± 14.65 mmHg (p = 0.013), respectively. The 6 months following discharge Glasgow outcome scale extended of patients was 4.73 ± 2.28 and 3.14 ± 2.15 (p = 0.027), respectively. CONCLUSION Our study reveals that basal cisternostomy in patients with surgically treated severe TBI has demonstrated significant efficacy in reducing intracranial pressure as well as patient prognosis follow-up and avoids removal of the bone flap. The efficacy of cisternostomy has to be studied in larger, multi-clinical center randomized trials.
Humans ; Brain Injuries, Traumatic/surgery* ; Retrospective Studies ; Male ; Female ; Adult ; Middle Aged ; Decompressive Craniectomy/methods* ; Aged ; Young Adult ; Adolescent ; Glasgow Coma Scale ; Treatment Outcome

IgA nephropathy (IgAN) is a glomerulonephritis characterized by diffuse deposition of immune complexes mainly composed of IgA in the mesangial area of the glomerulus. However, some patients show monotypic IgA deposits in the immunofluorescence examination, and its clinicopathological significance is not yet clear. The renal pathological changes of IgAN with monotypic IgA deposition are similar to those of proliferative glomerulonephritis with monoclonal IgA deposit (IgA-PGNMID), which has a risk of progressing to hematological malignancies and a worse clinical prognosis. It is necessary to differentiate them based on clinical pathological manifestations and hematological examinations. Based on previous literature reports and the research results of our research group, this review summarizes and analyzes the mechanism, clinical and pathological characteristics, and prognosis of IgAN with monotypic IgA deposition, and the relationship between IgAN with monotypic IgA deposition and IgA-PGNMID, to improve clinical doctors' understanding of IgAN with monotypic IgA deposition, reduce missed diagnosis and misdiagnosis, and improve patients' prognosis.

Sarcomatoid carcinoma of the renal pelvis accounts for a very low percentage of malignant tumors in the renal pelvis and has a poor prognosis. This article reported a patient with sarcomatoid carcinoma of the renal pelvis. The patient presented with macroscopic hematuria as the first symptom, and CT suggested left renal occupancy, unilateral nephrectomy was performed, and pathology suggested sarcomatoid carcinoma of the renal pelvis. Three weeks after surgery, a follow-up CT showed tumor recurrence. Programmed death 1(PD-1)inhibitor was given once every 3 weeks. Repeated CT examination after 24 weeks of continuous treatment suggested that the recurrent tumor disappeared. The patients was followed-up for 42 months without tumor recurrence or metastasis.

BACKGROUND:Patients with severe lumbar degenerative disease may have their bone mineral density incorrectly raised by dual-energy X-ray absorptiometry.While lumbar cancellous bone Hounsfield unit value can assist dual-energy X-ray absorptiometry in reducing osteoporosis misdiagnosis. OBJECTIVE:To identify osteoporosis in woman patients with lumbar degenerative diseases using lumbar CT scans. METHODS:Bone mineral density test results and lumbar CT data of 192 women patients who were treated at the Department of Spine Surgery,Sixth Affiliated Hospital of Xinjiang Medical University were retrospectively reviewed.All patients were divided into a degeneration group(n=107)and a control group(n=85)according to the criteria of severity of vertebral degeneration as assessed on CT of the lumbar spine.The CT value of axial cancellous bone of L1 vertebral body was measured in the two groups.The T score and bone mineral density of the hip and L2-L4 were recorded.According to previously published studies,osteoporosis was diagnosed at L1 vertebral CT values≤110.The prevalence of osteoporosis diagnosed by dual-energy X-ray absorptiometry and CT values was compared between the two groups. RESULTS AND CONCLUSION:(1)CT values were significantly and positively correlated with T scores and mean bone mineral density of the L2-L4 vertebrae in both groups(P<0.001),while the correlation was higher in the control group.(2)Lumbar T scores and bone mineral density values were significantly higher in the degeneration group than those in the control group(P<0.05)and CT values were significantly lower in the degeneration group than that in the control group(P = 0.001).Hip T scores and bone mineral density were not significantly different in the two groups.(3)The prevalence of osteoporosis diagnosed by CT thresholds was higher in all patients than that diagnosed by T values(51.0%and 42.7%).(4)The prevalence of osteoporosis diagnosed by CT values was as high as 23.6%in the 110 patients diagnosed with non-osteoporosis by dual energy X-ray absorptiometry in both groups,and was higher in the degeneration group than that in the control group(31.7%and 14.0%,respectively).(5)The prevalence of missed osteoporosis was as high as 38.6%(27/70)of non-osteoporosis patients diagnosed by dual-energy X-ray absorptiometry of the lumbar spine in the degeneration group compared to 19.6%(11/56)in the control group.(6)It is concluded that osteoporosis is common in female patients with lumbar degenerative diseases aged≥50 years.Measurement of lumbar cancellous bone CT values may be a useful complementary method for diagnosing osteoporosis in patients with lumbar degenerative diseases,especially in patients with severe degenerative lumbar degenerative diseases where more missed osteoporosis patients can be identified.

Objective To investigate the regulatory effect and mechanism of new skeleton small molecule compound ZHZ-33-1 on the inflammatory response induced by primary macrophages in mice infected by Staphylococcus aureus.Methods qRT-PCR was used to detect the mRNA expression levels of inflammatory factors Tnf,Illb,116,Il12p40 in macrophages cells.The protein levels of TNF-α,IL-1 β,IL-6 and IL-12 in cell supernatant were determined by ELISA.Western blot was used to analyze the phosphorylation of key signaling pathway proteins such as NF-κB and MAPK.CCK8 detection was used to evaluate the effect of ZHZ-33-1 on macrophages activity.The OD600nm method was used to investigate the effect of ZHZ-33-1 on the growth of Staphylococcus aureus.Results 80 pmol/L ZHZ-33-1 had no significant effect on bacterial proliferation(P＞0.05)and cytotoxicity of macrophages(P＞0.05).Compared with the DMSO group,ZHZ-33-1 significantly inhibited the transcription and expression levels of inflammatory cytokines(TNF-α,IL-iβ,IL-6,and IL-12)in primary macrophages infected by Staphylococcus aureus(USA300)(P＜0.05).Further studies showed that ZHZ-33-1 was able to inhibit the NF-κB and MAPK pathways of wild macrophages,but was not TLR2-/-macrophages.Conclusion Through inhibiting NF-κB and MAPK signaling pathways,ZHZ-33-1 may inhibit the macrophages inflammatory response caused by Staphylococcus aureus.Therefore,ZHZ-33-1 is expected to become a new drug candidate for the treatment of Staphylococcus aureus-induced hyperinflammatory response.

Objective:To assess the impact of the construction of smoke-free government on the smoking and cessation behaviors of staff members.Methods:This was a retrospective cohort study. The study used stratified random cluster sampling method to select 144 government institutions from 31 Provinces (Autonomous Regions and Municipalities) and the Xinjiang Production and Construction Corps. The survey was carried out between October and November, 2023 by filling out questionnaires online among the insiders of the institutions and all the smoking staff members. The main indicators included the number of smokers before and after the construction of smoke-free governments and the measures for the construction of smoke-free governments. 144 questionnaires from insiders were recovered, all of which were included in the analysis; 1 776 questionnaires from smokers were recovered, including 1 716 valid questionnaires. The SAS 9.4 was used to perform χ 2 test and log-binomial regression analysis. Results:The percentage of smoking staff members decreased from 8.81% before the construction to 6.70% after the construction, and the difference was statistically significant ( χ 2=63.23, P<0.001). Comprehensive smoking ban in indoor public places ( OR=2.301, 95% CI: 1.433-3.694), punishment mechanism for smoking staff members ( OR=1.219, 95% CI: 1.124-1.322), smoking cessation competitions ( OR=1.865, 95% CI: 1.234-2.818) and reimbursement for or provision of smoking cessation medications ( OR=2.210, 95% CI: 1.002-4.874) were facilitators to motivate the smoking staff members to quit (all P<0.01). Numbers of smoking leaders ( OR=0.858, 95% CI: 0.807-0.913) and smoking years of smoking staff members ( OR=0.932, 95% CI: 0.918-0.946) negatively influenced the smoking staff members to quit (both P<0.001). Conclusions:The construction of smoke-free governments can effectively promote the smoking cessation behaviors of smoking staff members. In addition, comprehensive smoke-free policies, punishment mechanism for smoking staff members and activities such as smoking cessation competitions, and reimbursement for or provision of smoking cessation medications are important.

Objective:To investigate the role of dopamine receptors in the central amygdala (CeA) in reduction of the anxiety level by propofol in a mouse model of post-traumatic stress disorder (PTSD).Methods:Fifty-six SPF healthy adult male C57BL/6 mice, aged 10 weeks, weighing 20-25 g, were divided into 7 groups ( n=8 each) using a random number table method: control group (C group), PTSD group (P group), PTSD+ propofol group (PP group), PTSD+ fat emulsion group (PF group), PTSD+ propofol+ normal saline group (PPN group), PTSD+ propofol+ dopamine receptor D1 (DRD1) antagonist group (PP+ DRD1-Ant group), and PTSD+ propofol+ DRD2 antagonist group (PP+ DRD2-Ant group). The PTSD model was developed by continuous plantar electric shock for 3 days. Propofol 120 mg/kg was intraperitoneally injected after successful establishment of the model in PP group, and the equal volume of fat emulsion was intraperitoneally injected in PF group. In PPN group, PP+ DRD1-Ant group and PP+ DRD2-Ant group, the equal volume of normal saline, DRD1 antagonist hydrochloride and DRD2 antagonist eticlopride hydrochloride were injected in bilateral CeA regions, respectively, 30 min later the efficacy of drugs reached the peak, and then propofol 120 mg/kg was intraperitoneally injected. The anxiety levels were measured at 4 h (T 1) and day 3 after propofol injection (T 2) by the open field test and elevated cross maze test. Results:Compared with C group, the time spent entering the open and central areas was significantly shortened at T 1, 2, and the number of entering the open and central areas was decreased at T 1, 2 in P group ( P<0.001). Compared with P group, the time spent entering the open and central areas was significantly prolonged at T 1, the number of entering the open and central areas was increased at T 1 ( P<0.001), and no significant change was found at T 2 in PP group ( P>0.05), and no significant change was found in the aforementioned parameters at T 1, 2 in PF group ( P>0.05). Compared with PPN group, the time spent entering the open and central areas was significantly shortened at T 1, and the number of entering the open and central areas was decreased at T 1 in PP+ DRD2-Ant group ( P<0.001), and no significant change was found at T 1 in PP+ DRD1-Ant group ( P>0.05). Conclusions:Activation of DRD2 in the CeA is involved in the process by which propofol reduces the anxiety level of mice with PTSD.