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*

Objective:To investigate the expression characteristics of the SLFN11 gene in pancreatic cancer and its relationship with cis-diamminedichloroplatinum(DDP)resistance.Methods:This study analyzed multiple publicly available datasets, including GSE207611, GSE186205, GSE73978, GSE217845, and GSE238163 from the gene expression omnibus(GEO)datasets.These datasets comprise gene expression data and single-cell sequencing data from pancreatic cancer cell lines and patients, which were utilized to examine the expression characteristics of the SLFN11 gene and its association with cisplatin resistance.Receiver operating characteristic (ROC) curves were generated, and the area under the curve (AUC) value along with the confidence interval ( CI) were calculated.Additionally, Kaplan-Meier survival analysis and single-cell RNA sequencing(scRNA-seq)data analysis were conducted. Results:The differential expression of the SLFN11 gene between tumor and adjacent normal tissues was statistically significant( P<0.05). The AUC value for SLFN11 in diagnosing pancreatic cancer was 0.761.SLFN11, along with its associated genes PTN and SLC15A3, collectively influenced the survival of pancreatic cancer patients.Results from single-cell sequencing demonstrated high expression of SLFN11 in mesenchymal stem cells. Conclusions:The SLFN11 gene demonstrates significant diagnostic and prognostic value in pancreatic cancer and may play a role in the mechanism of cisplatin resistance.

Objective:To explore the anesthetic effect of butorphanol combined with ropivacaine iliac fascia space block and femoral nerve combined with lateral femoral cutaneous nerve block in tibiofibular fracture surgery.Methods:A total of 86 patients with tibiofibular fractures admitted to the Sun Simiao Hospital of Beijing University of Chinese Medicine and Tongchuan Mining Bureau Central Hospital from December 2022 to December 2023 were selected and divided into observation group and control group by random number table method, with 42 cases in each group. The control group was given femoral nerve combined with lateral femoral cutaneous nerve block anesthesia, and the observation group was given iliac fascia space block anesthesia. The changes of heart rate (HR) and peripheral capillary oxygen saturation (SpO 2) at different time points during operation (before nerve block, 15 min after nerve block, 5 min before the end of operation) were compared between the two groups. The Visual Analogue Scale (VAS) was used to evaluate the pain degree at 6 h and 24 h after operation. The serum levels of prostaglandin E 2 (PGE 2), catalase (CAT) and superoxide dismutase (SOD) were compared between the two groups before operation and 24 h after operation. The duration of sensory block and motor nerve block after operation were recorded. The occurrence of postoperative complications was recorded. Results:There were no significant differences in HR and SpO 2 between the two groups at different time points during operation (all P>0.05). The VAS scores at 24 h after operation in both groups were lower than those at 6 h after operation (all P<0.05). At 6 h and 24 h after operation, the VAS scores of pain in the observation group were lower than those in the control group (all P<0.05). The serum CAT and SOD levels at 24 h after operation in both groups were lower than those before operation, and the serum PGE 2 levels were higher than those before operation, the serum CAT and SOD levels at 24 h after operation in the observation group were higher than those in the control group (all P<0.05), and the serum PGE 2 in the observation group was lower than that in the control group ( P<0.05). The motor nerve block time in the observation group was shorter than that in the control group, and the sensory block duration was longer than that in the control group (all P<0.05). There were 3 cases of nausea and 1 case of vomiting in the observation group, and 4 cases of nausea, 1 case of vomiting and 1 case of delirium in the control group. There was no significant difference in the incidence of complications between the two groups [9.52%(4/42) vs 14.29%(6/42), P>0.05]. Conclusions:Compared with femoral nerve combined with lateral femoral cutaneous nerve block, the iliac fascia space block anesthesia applied in the anesthetic management of tibiofibular fracture surgery has more stable intraoperative analgesic and sedative effects, helps to reduce the degree of postoperative pain, and has good safety.

Objective:To investigate the expression characteristics of the SLFN11 gene in pancreatic cancer and its relationship with cis-diamminedichloroplatinum(DDP)resistance.Methods:This study analyzed multiple publicly available datasets, including GSE207611, GSE186205, GSE73978, GSE217845, and GSE238163 from the gene expression omnibus(GEO)datasets.These datasets comprise gene expression data and single-cell sequencing data from pancreatic cancer cell lines and patients, which were utilized to examine the expression characteristics of the SLFN11 gene and its association with cisplatin resistance.Receiver operating characteristic (ROC) curves were generated, and the area under the curve (AUC) value along with the confidence interval ( CI) were calculated.Additionally, Kaplan-Meier survival analysis and single-cell RNA sequencing(scRNA-seq)data analysis were conducted. Results:The differential expression of the SLFN11 gene between tumor and adjacent normal tissues was statistically significant( P<0.05). The AUC value for SLFN11 in diagnosing pancreatic cancer was 0.761.SLFN11, along with its associated genes PTN and SLC15A3, collectively influenced the survival of pancreatic cancer patients.Results from single-cell sequencing demonstrated high expression of SLFN11 in mesenchymal stem cells. Conclusions:The SLFN11 gene demonstrates significant diagnostic and prognostic value in pancreatic cancer and may play a role in the mechanism of cisplatin resistance.

Objective:To explore the anesthetic effect of butorphanol combined with ropivacaine iliac fascia space block and femoral nerve combined with lateral femoral cutaneous nerve block in tibiofibular fracture surgery.Methods:A total of 86 patients with tibiofibular fractures admitted to the Sun Simiao Hospital of Beijing University of Chinese Medicine and Tongchuan Mining Bureau Central Hospital from December 2022 to December 2023 were selected and divided into observation group and control group by random number table method, with 42 cases in each group. The control group was given femoral nerve combined with lateral femoral cutaneous nerve block anesthesia, and the observation group was given iliac fascia space block anesthesia. The changes of heart rate (HR) and peripheral capillary oxygen saturation (SpO 2) at different time points during operation (before nerve block, 15 min after nerve block, 5 min before the end of operation) were compared between the two groups. The Visual Analogue Scale (VAS) was used to evaluate the pain degree at 6 h and 24 h after operation. The serum levels of prostaglandin E 2 (PGE 2), catalase (CAT) and superoxide dismutase (SOD) were compared between the two groups before operation and 24 h after operation. The duration of sensory block and motor nerve block after operation were recorded. The occurrence of postoperative complications was recorded. Results:There were no significant differences in HR and SpO 2 between the two groups at different time points during operation (all P>0.05). The VAS scores at 24 h after operation in both groups were lower than those at 6 h after operation (all P<0.05). At 6 h and 24 h after operation, the VAS scores of pain in the observation group were lower than those in the control group (all P<0.05). The serum CAT and SOD levels at 24 h after operation in both groups were lower than those before operation, and the serum PGE 2 levels were higher than those before operation, the serum CAT and SOD levels at 24 h after operation in the observation group were higher than those in the control group (all P<0.05), and the serum PGE 2 in the observation group was lower than that in the control group ( P<0.05). The motor nerve block time in the observation group was shorter than that in the control group, and the sensory block duration was longer than that in the control group (all P<0.05). There were 3 cases of nausea and 1 case of vomiting in the observation group, and 4 cases of nausea, 1 case of vomiting and 1 case of delirium in the control group. There was no significant difference in the incidence of complications between the two groups [9.52%(4/42) vs 14.29%(6/42), P>0.05]. Conclusions:Compared with femoral nerve combined with lateral femoral cutaneous nerve block, the iliac fascia space block anesthesia applied in the anesthetic management of tibiofibular fracture surgery has more stable intraoperative analgesic and sedative effects, helps to reduce the degree of postoperative pain, and has good safety.

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 explore the mechanism which drives nimbolide(NIM)in treating acute pneumonia caused by Staphylococcus aureus(S.auteus).Methods A mouse model of acute pneumonia caused by S.auteus was constructed through endotracheal intubation.After NIM treatment,the survival rate was observed,the amount of bacteria in the lung was tested by plate culture,and the expression of inflammatory cytokines in the lung tissues was detected with ELISA.After primary cultured peritoneal macrophages(PM)were infected with S.auteus,the effect of NIM on the expression of inflammatory cytokines and activation of inflammatory pathway were studied with ELISA and Western blotting,respectively.The effect of RNF114 knockdown by lentiviral shRNA infection on inflammation responses in PM was explored with ELISA and Western blotting.Results Acute infection of S.auteus in the lung could cause acute death in the mice,while NIM treatment significantly improved the survival rate and down-regulated the levels of inflammatory cytokines in the lung.However,it had no effect on the lung colonization of S.auteus in the short term.The results of in vitro experiments indicated that NIM may regulate RNF114 function to down-regulate the phosphorylation level of ERK,inhibit the activation of MAPK pathway,and thus suppress the expression of inflammatory cytokines.Conclusion NIM may inhibit the activation of MAPK pathway by regulating the function of RNF114,and thus suppress the expression of inflammatory cytokines in the lung,and finally inhibit the death of mice with acute pulmonary hyperinflammation caused by S.auteus.

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.

Purpose: Loss-of-function mutations in the adenomatous polyposis coli (APC) gene are common in metastatic colorectal cancer (mCRC). However, the characteristic of APC specific mutations in mCRC is poorly understood. Here, we explored the clinical and molecular characteristics of N-terminal and C-terminal side APC mutations in Chinese patients with mCRC. Materials and Methods: Hybrid capture-based next-generation sequencing was performed on tumor tissues from 275 mCRC pati-ents to detect mutations in 639 tumor-associated genes. The prognostic value and gene-pathway difference between APC specific mutations in mCRC patients were analyzed. Results: APC mutations were highly clustered, accounting for 73% of all mCRC patients, and most of them were truncating mutations. The tumor mutation burden of the N-terminal side APC mutations group (n=76) was significantly lower than that of the C-terminal side group (n=123) (p < 0.001), further confirmed by the public database. Survival analysis showed that mCRC patients with N-terminus side APC mutations had longer overall survival than C-terminus side. Tumor gene pathway analysis showed that gene mutations in the RTK/RAS, Wnt and transforming growth factor β signaling pathways of the C-terminal group were significantly higher than those of the N-terminal group (p < 0.05). Additionally, KRAS, AMER1, TGFBR2, and ARID1A driver mutations were more common in patients with C-terminal side APC mutations. Conclusion APC specific mutations have potential function as mCRC prognostic biomarkers. There are obvious differences in the gene mutation patterns between the C-terminus and N-terminus APC mutations group, which may have certain guiding significance for the subsequent precise treatment of mCRC.

Objective To investigate the efficacy of precise ultrasound-guided stellate ganglion block(UG-SGB)combined with ozonated autohemotherapy in the treatment of sudden hearing loss.Methods Fifty-seven patients with sudden hearing loss,27 males and 30 females,aged 19-82 years,BMI 20-29 kg/m2,ASA physical status Ⅰ or Ⅱ,were randomly divided into drugs combined with UG-SGB and ozonated autohemotherapy treatment group(group U,n=29)and drugs group(group D,n=28)accord-ing to the random number table.All patients were given drug therapy.In addition to the treatment above,pa-tients in group U also received precise ultrasound-guided stellate ganglion block once on affected side com-bined with ozonated autohemotherapy once daily for 10 consecutive days.Patients in group D received drug therapy only.The average hearing threshold of the two groups was compared before treatment(T0),at dis-charge(T1),1 month(T2),3 months(T3),and 6 months after discharge(T4).The hearing improve-ment of the two groups was also compared at T1-T4 on the basis of T0.Moreover,tinnitus rate of the two groups was recorded T0-T4.In addition,adverse reactions such as toxicosis of local anaesthetics,pneumo-thorax were recorded.Results Compared with T0,the average hearing threshold was reduced significantly in both groups at T1-T4(P＜0.05),the incidence of tinnitus was reduced significantly at T1-T4 in both groups(P＜0.05).Compared with T,,the average hearing threshold was reduced significantly in group U at T2-T4(P＜0.05).The average hearing threshold of group U was lower than that in group D at T1-T4(P＜0.05).The hearing improvement in group U was better than that in group D at T2-T4(P＜0.05).The proportion of complete hearing recovery in group U was increased significantly than that in group D at T2-T4(P＜0.05)The proportion of effective hearing improvement in group U was decreased than that in group D at T3-T4(P＜0.05).No obvious adverse reaction was recorded,such as toxicosis of local anaesthetics,pneumothorax.Conclusion Precise ultrasound-guided stellate ganglion block combined with ozonated auto-hemotherapy based on drug treatment significantly improves the average hearing threshold of patients with sudden hearing loss in acute stage and improve their hearing.