In the ever-evolving landscape of cancer therapy, while cancer treatments such as chemotherapy, radiotherapy, and targeted therapy aim to eradicate malignant cells, they also inadvertently trigger cellular senescence in both cancerous and microenvironmental tissues. Therapy-induced senescence (TIS) can act as a barrier against tumor growth by halting cell proliferation in the short term, but the long-term persistence of therapy-induced senescent (TISnt) cells may pose a significant challenge in cancer management. Their distinct characteristics, like senescence-associated secretory phenotype (SASP), metabolic dysregulation, and immune evasion, make them exhibit remarkable heterogeneity to orchestrate the tumor microenvironment (TME), resulting in therapy resistance. However, how these TISnt cells functioning differently in cancer progression, and the intricate mechanisms by which they remodel the senescence-associated immunosuppressive microenvironment present challenges for improving anticancer therapy. Therefore, this review summarizes the heterogeneous TISnt cell phenotypes contributing to an accumulated senescent state, outlines their multidimensional interactions in the senescent microenvironment, and discusses current senescence-targeting strategies. Building on the current understanding of TIS, we propose potential avenues for improving TIS-targeting methodologies in the context of head and neck cancer, a representative heterogeneous malignancy, which can substantially enhance the efficacy of the "one-two punch" sequential treatment approach for head and neck cancer.
Humans ; Cellular Senescence/drug effects* ; Tumor Microenvironment ; Neoplasms/pathology* ; Senescence-Associated Secretory Phenotype

As the most common type of protein glycosylation, N-glycosylation begins with the synthesis of the dolichol-linked oligosaccharide (DLO) precursor in the endoplasmic reticulum. The mannosyltransferase Alg1 catalyzes the addition of the first mannose molecule to DLO, serving as a key enzyme in this biochemical pathway. The defect of human ALG1 gene can lead to the congenital disorders of glycosylation (CDG), i.e., ALG1-CDG. Therefore, it is of great significance to establish the expression and activity assay system of Homo sapiens Alg1 (HsAlg1) in vitro. In this study, full-length plasmid pET28a-His6-HsAlg1 and transmembrane domain-lacking plasmid pET28a-His6-HsAlg1_23-464 were constructed and expressed in Escherichia coli, and the activity of recombinant HsAlg1 and HsAlg1_23-464 was measured by liquid chromatography tandem mass spectrometry (LC-MS) with dolichyl-pyrophosphate GlcNAc2 (DPGn2) as the substrate. The results showed that HsAlg1 had transglycosylation activity, while the activity decreased after protein purification, which was partially restored upon re-addition of membrane components. However, HsAlg1_23-464 was unable to catalyze glycosylation. The results indicate that the N-terminal transmembrane domain (TMD) of HsAlg1 plays an important role in the catalytic reaction. This study lays a foundation for further expression and activity analysis of ALG1-CDG-related mutants.
Humans ; Escherichia coli/metabolism* ; Mannosyltransferases/biosynthesis* ; Glycosylation ; Recombinant Proteins/metabolism* ; Protein Domains

Objective:To explore the clinical characteristics of children with septic shock and analyze the drug resistance of blood culture positive bacteria.Methods:The clinical data,positive blood culture strains and drug sensitivity results of 127 children with septic shock admitted to the Department of Intensive Care Medicine of Hunan Children's Hospital from September 2015 to August 2021 were retrospectively analyzed.Results:A total of 134 strains of bacteria or fungi were isolated from the blood culture samples of 127 children with septic shock,and gram-negative strains were the main ones,accounting for 67.16% (90/134).Haemophilus influenzae and Escherichia coli were the main gram-negative bacteria,accounting for 38.81% (52/134) and 20.15% (27/134)，respectively,while Streptococcus pneumoniae was the main gram-positive bacteria,accounting for 8.21% (11/134),and Candida albicans was the main fungus,accounting for 10.45% (14/134).The number of white blood cells,the levels of serum C-reactive protein,procalcitonin,venous blood sugar and arterial blood lactic acid in patients were all significantly higher than normal values,and the white blood cells count and neutrophil percentage in gram-positive bacterial infections were significantly higher than those with gram-negative bacterial infections and fungal infections( P<0.05).Procalcitonin increased most obviously when infected by gram-negative bacteria,and the difference was statistically significant ( P<0.05).Gram-positive strains were sensitive to vancomycin,teicoplanin,and linezolid,but only 50% of Streptococcus pneumoniae were sensitive to penicillin.Gram-negative strains had relatively high drug resistance,among which Klebsiella pneumoniae were only highly resistant to imipenem,cilastatin and levofloxacin,reaching 50%.Haemophilus influenzae was resistant to cephalosporins and β-amides enzyme antibiotic,and the drug sensitivity rate of lactamase antibiotics was high,with a resistance rate of 50% only to ampicillin,cefuroxime,amikacin,and compound sulfamethoxazole.There were not many fungal strains,and most antifungal drugs were effective against blood culture-positive fungi. Conclusion:The main pathogens of infection in children with septic shock are gram-negative bacteria,and have high resistance to general antibiotics.We should pay attention to their drug resistance when using antibiotics empirically.

Objective To evaluate the early imaging characteristics and function of bladder wall reconstruction neourethra(BWN)after robot-assisted laparoscopic prostatectomy(RALP)for prostate cancer with magnetic resonance imaging(MRI)and voiding cystourethrography(VCUG).Methods A total of 36 patients who underwent RALP using BWN technique at Taizhou People's Hospital during Mar.2021 and Jun.2023 were enrolled.Postoperative MRI was used to measure the length,wall thickness,and lumen shape of the new urethra.The morphology of the new urethra in 19 patients was observed under VCUG during the storage phase,voiding phase,and interrupted voiding phase.Results The patients'median age was 73.00 years(range:68.00 to 76.25),the prostate volume was(45.01±7.18)cm3,and the median total prostate-specific antigen(tPSA)level was 10.77 ng/mL(range:7.30 to 14.86).Two patients were classified as T1 stage,25 as T2,and 9 as T3.Gleason scores were ≤6 in 7 patients and ≥8 in 8 patients.Risk classification was low risk in 2 patients and high risk in 8 patients.Postoperatively,urinary control rates at 1,3,and 6 months were 91.67％,97.22％,and 100％,respectively.MRI revealed a median new urethra length of 15.13 mm(range:12.71 to 20.26)and a median wall thickness of 6.84 mm(range:6.18 to 8.20).The urethral lumen had a complete muscular layer and mucosal layer,which appeared petal-like.In patients with urinary incontinence,residual urine was visible in the new urethra and at the anastomosis site.Of the 19 patients who underwent VCUG,16 could close the new urethra during the storage and interrupted voiding phases,and open it during the voiding phase;3 could not close it well during the storage and interrupted voiding phases.Conclusion MRI and VCUG clearly demonstrate that the BWN technique can successfully create a new urethra with good functionality,which helps improve urinary control after RALP for prostate cancer.

Lumbar disc herniation (LDH) is a common clinical spine disease, which can lead to lower limb pain, weakness, numbness and even tingling and burning nerve paraesthesia, seriously affecting the quality of life of the patients. At present, X-ray, CT and MRI are commonly used in clinical imaging. However, in the process of diagnosis and treatment of LDH, clinical symptoms often do not coincide with imaging results, and MRI cannot show the degree of nerve injury. MRI diffusion imaging technique is currently the only method to measure the diffusion motion and imaging of water molecules in vivo, mainly including diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI). In recent years, with the improvement of pulse sequence technology and the application of high-intensity magnetic field, MRI diffusion imaging technology has been gradually applied to the diagnosis and treatment of lumbar nerve injury, which can obtain non-invasive images of the stenosis or interruption of the involved nerve fibers. Based on the principle of diffusion imaging technology, this article analyzes the current status of its application in the diagnosis and treatment of LDH, and analyzes its limitations and discusses the future development direction, in order to provide basis and ideas for the realization of accurate diagnosis and treatment of LDH.

This study aims to promote the system construction of public health talent through understanding the status and identifying problems of public health human resources in Weihai City. A survey on professional public health institutions was conducted through questionnaires and interviews in Weihai City, and statistical analysis on the personnel structure, introduction, and turnover of professional public health institutions was conducted. There were 24 professional public health institutions in Weihai City, with a vacancy rate of 44.27% (1 367/3 088). Health professionals accounted for 68.09% (1 669/2 451) of the on-duty personnel. The number of health technicians in professional public health institutions in the city was 0.57 per thousand people. Among the 1 669 health professionals, the age groups≤35, 36-45, 46-54, and ≥55 accounted for 47.63% (795/1 669), 30.26% (505/1 669), 18.10% (302/1 669), and 4.01% (67/1 669), respectively. The personnel with bachelor′s degrees and master′s degrees accounted for 74.60% (1 245/1 669) and 8.09% (135/1 669). The personnel holding clinical medical, nursing, laboratory, and public health qualifications accounted for 61.34% (995/1 622), 28.30% (459/1 622) and 10.36% (168/1 622), respectively. Only 17.73% (296/1 669) of personnel held deputy senior or above technical titles, while 45.96% (767/1 669) held junior or below technical titles. About 70.10% (1 170/1 669) personnel held permanent positions, and 29.90% (499/1 669) held non-permanent positions. From 2021 to 2023, the employment rate of public health institutions was 65.51% (207/316), and the ratio of introduced and lost personnel was approximately 3∶2 (207/132).

Objective:To investigate the current situation of key endemic disease prevention and control in Shanxi Province, and provide a scientific basis for further strengthening the implementation of prevention and control measures.Methods:In 2021, monitoring of key endemic disease prevention and control projects in Shanxi Province was carried out in accordance with the current national monitoring plans for iodine deficiency disorders and water source high iodine areas, for endemic fluorosis, endemic arsenic poisoning, Kashin-Beck disease, and Keshan disease. The effect of prevention and control measures was evaluated in accordance with the "Evaluation Measures for Key Endemic Disease Control and Elimination (2019 Edition)". Patient management services and treatment subsidy projects were carried out in accordance with the "Management Service Standards for Endemic Disease Patients" and the "Management Measures for Treatment of Endemic Disease Patients".Results:All 117 counties (cities, districts, hereinafter referred to as counties) in Shanxi Province had reached the national elimination standards for iodine deficiency disorders, and the overall iodine nutrition of the population was generally suitable. However, the consumption rate of qualified iodine salt in 8 counties was ≤90%, and the iodine nutrition of pregnant women in 13 counties was insufficient. The water improvement rate in 295 villages in 12 counties across the province with high water iodine level was 80.68% (238/295), and the proportion of villages with qualified water iodine after water improvement was 38.31% (113/295). The prevention and control measures of 93.55% (58/62) of the counties in the province with endemic fluorosis caused through drinking water reached the national control standards. Totally 20 counties ravaged by coal-burning borne endemic fluorosis, 16 counties ravaged by drinking water borne endemic arsenicosis (high arsenic areas), 35 counties ravaged by Kashin-Beck disease, and 11 counties ravaged by Keshan disease met the national elimination standards. In 2021, 11 197 patients with endemic diseases were followed up and managed in Shanxi Province, and drug treatment programs were carried out on 3 413 patients with skeletal fluorosis, 2 088 patients with Kashin-Beck disease, and 10 patients with chronic Keshan disease.Conclusions:The overall prevention and control of key endemic diseases in Shanxi Province remains under control or elimination. However, the water improvement in some drinking water borne endemic fluorosis areas still needs to be further strengthened. Measures for water improvement and supply of non-iodized salt in water source high iodine areas still need to be coordinated and promoted. Key endemic disease patients in Shanxi Province have basically achieved standardized management.

Objective:To explore the risk factors of oral-mucosal pressure injury (OMPI) in patients with tracheal intubation in ICU and to establish a nomogram model.Methods:Using the convenient sampling method, a total of 640 patients with oral tracheal intubation admitted to ICU of the First Affiliated Hospital of Xinjiang Medical University from January to May 2023 were selected as the research objects. They were divided into the occurrence group ( n=286) and the non-occurrence group ( n=354) according to whether OMPI occurred or not. Binomial Logistic regression analysis was used to explore the risk factors for OMPI in patients with tracheal intubation in ICU. A risk nomogram model was created based on independent risk factors, and internal verification was conducted by Bootstrap repeated sampling method. Results:OMPI occurred in 286 of 640 ICU patients with tracheal intubation. Binomial Logistic regression analysis showed that high APACHEⅡ score, modified Beck oral score greater than or equal to 11 points, use of sedative drugs, prone ventilation, long retention time of tracheal catheter, low oxygenation index less than 200 mmHg (1 mmHg=0.133 kPa) and tracheal catheter fixation frequency of 1 time /24 h were the risk factors for OMPI in patients with tracheal intubation in ICU ( P<0.05). A risk nomogram model for OMPI in patients with tracheal intubation in ICU was established based on independent risk factors. The results showed that the predictive performance (area under the receiver operating characteristic curve of subjects was 0.918, 95% confidence interval was 0.897 to 0.938) and calibration (χ 2 value of 4.647, P=0.795) of the risk nomogram model for OMPI in patients with tracheal intubation in ICU were good. When the threshold probability was 0 to 1, the decision curve showed that the model had good clinical effectiveness. Conclusions:The OMPI risk nomogram model of tracheal intubation patients in ICU established in this study has good calibration and differentiation, which can be used as an effective tool for screening high-risk patients.

This study aims to promote the system construction of public health talent through understanding the status and identifying problems of public health human resources in Weihai City. A survey on professional public health institutions was conducted through questionnaires and interviews in Weihai City, and statistical analysis on the personnel structure, introduction, and turnover of professional public health institutions was conducted. There were 24 professional public health institutions in Weihai City, with a vacancy rate of 44.27% (1 367/3 088). Health professionals accounted for 68.09% (1 669/2 451) of the on-duty personnel. The number of health technicians in professional public health institutions in the city was 0.57 per thousand people. Among the 1 669 health professionals, the age groups≤35, 36-45, 46-54, and ≥55 accounted for 47.63% (795/1 669), 30.26% (505/1 669), 18.10% (302/1 669), and 4.01% (67/1 669), respectively. The personnel with bachelor′s degrees and master′s degrees accounted for 74.60% (1 245/1 669) and 8.09% (135/1 669). The personnel holding clinical medical, nursing, laboratory, and public health qualifications accounted for 61.34% (995/1 622), 28.30% (459/1 622) and 10.36% (168/1 622), respectively. Only 17.73% (296/1 669) of personnel held deputy senior or above technical titles, while 45.96% (767/1 669) held junior or below technical titles. About 70.10% (1 170/1 669) personnel held permanent positions, and 29.90% (499/1 669) held non-permanent positions. From 2021 to 2023, the employment rate of public health institutions was 65.51% (207/316), and the ratio of introduced and lost personnel was approximately 3∶2 (207/132).

The characteristic features of dissociative conversion disorder entail a partial or complete loss of normal integration in memory,identity awareness,immediate sensation,and motor control.This article documents a case of the disorder presenting with an onset of depressive mood,diminished interest,and facial tics,subsequently accompanied by intermittent fainting spells with limb convulsions.Despite multiple consultations in both general hospitals and psychiatric settings,and despite treatment with various antidepressants and antiepileptic medications,the patient's symptoms showed no significant improvement.The report of this case deepens the understanding of a complex and commonly misdiagnosed condition,offering valuable insights for the diagnosis and treatment of patients exhibiting similar symptoms.