Objective Zinc finger protein 335 (Zfp335) plays a crucial role in the early development of thymic T cells and the differentiation of peripheral T cell subpopulations. The objective of this study is to investigate the role and underlying mechanisms of Zfp335 in the regulation of regulatory T cell (Treg) within tumor immunity. Methods The Zfp335 gene was specifically knocked out in Treg using tamoxifen (Zfp335^fl/fl FOXP3^creERT2), and the MC38 tumor model was established. On the 7th day after tumor inoculation, tumor size was observed and measured. Tumor size was monitored and recorded daily starting from day 7 post-inoculation. On day 12, tumors were harvested, and the proportions of CD4⁺ T cells, CD8⁺ T cells, and Treg were analyzed by flow cytometry. Additionally, the mitochondrial function of effector regulatory T cell (eTreg) was assessed. Results From day 10 post-tumor inoculation, tumor volume in the Zfp335^CKO group was significantly reduced compared to that of the wild-type (WT) group. Furthermore, the infiltration of CD4⁺ and CD8⁺ T cells, along with their respective effector cells, was significantly higher in the Zfp335^CKO group than in the WT group. The proportions of CD4⁺ and CD8⁺ T cells producing interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were also significantly increased in the Zfp335^CKO group compared to that of the WT group. In addition, the percentage of CD8⁺ T cells secreting granzyme B (GzmB) was significantly higher in the Zfp335^CKO group than that in the WT group. In contrast, the proportion of Treg and inducible T cell co-stimulator (ICOS)⁺ Treg in the Zfp335^CKO group was significantly lower than that in the WT group. Finally, the expression level of Mitotracker Deep Red in eTreg from the Zfp335^CKO group was significantly reduced compared to that in the WT group. Conclusion During tumorigenesis, the specific deletion of Zfp335 impairs Treg activation, which is related to decreased mitochondrial function in eTreg. In Zfp335^CKO mice. Tumors exhibit increased infiltration of effector T cells, accompanied by elevated levels of cytotoxic cytokines, ultimately enhancing resistance to tumor progression.
Animals ; T-Lymphocytes, Regulatory/metabolism* ; Mice ; CD8-Positive T-Lymphocytes/immunology* ; Neoplasms/genetics* ; Cell Line, Tumor ; Mice, Inbred C57BL ; Mice, Knockout ; DNA-Binding Proteins/genetics* ; Female

OBJECTIVE: To explore the effects of different endotracheal tube cuff pressure management modes on cuff sealing and the pressure exerted on the tracheal wall. METHODS: A prospective self-controlled study was conducted. Eleven patients undergoing endotracheal intubation and mechanical ventilation with an automatic airway management system (AGs) admitted to the Second Medical Centre of the Chinese People's Liberation Army General Hospital from October 1, 2020, to April 1, 2022, were enrolled as the study subjects. Within 24 hours after the establishment of artificial airway and mechanical ventilation, four cuff pressure management modes were randomly applied to each patient for 24 hours in sequence: automatic cuff pressure management mode [modeI: the safe range of cuff pressure was set at 20-35 cmH₂O (1 cmH₂O≈0.098 kPa), and the CO₂ pressure above the endotracheal tube cuff was automatically detected by AGs every 5 minutes to determine the cuff sealing status, and the cuff pressure was automatically adjusted], constant cuff pressure (25 cmH₂O) management mode (mode II: the cuff pressure was monitored by AGs through a pressure sensor, and the cuff pressure was maintained at 25 cmH₂O via a pressure pump), constant cuff pressure (30 cmH₂O) management mode (mode III: the cuff pressure was monitored by AGs through a pressure sensor, and the cuff pressure was maintained at 30 cmH₂O via a pressure pump), and manual cuff pressure management mode (mode IV: the cuff pressure was manually measured by nurses every 6-8 hours using a cuff pressure gauge to keep the cuff pressure at 25-30 cmH₂O after inflation). The CO₂ pressure above the endotracheal tube cuff (at 60-minute intervals) and the cuff pressure changes (at 50-ms intervals) were recorded to compare the differences in number of cuff leaks [no leak was defined as CO₂ pressure = 0, small leak as 0 < CO₂ pressure < 2 mmHg (1 mmHg≈0.133 kPa), and large leak as CO₂ pressure ≥ 2 mmHg] and cuff pressure among modesI-IV. RESULTS: A total of 24 CO₂ pressure measurements were taken per patient across the four modes, resulting in a total of 264 detections for each mode. Regarding the cuff leak, the total number of leak and large leak in modeIwas significantly lower than that in modes II-IV [total leak: 30 cases (11.36%) vs. 81 cases (30.68%), 70 cases (26.52%), 103 cases (39.02%); large leak: 15 cases (5.68%) vs. 50 cases (18.94%), 48 cases (18.18%), 66 cases (25.00%), all P < 0.05]. There was no significant difference in the number of cuff leak between modes II and III, and mode IV had the most severe cuff leak. In terms of cuff pressure, since mode IV required blocking the cuff tube from the AGs tube and the AGs cuff pressure management module did not actually work, real-time monitoring of cuff pressure was not possible. Therefore, cuff pressure changes were only analyzed in modes I-III. Each of the 11 patients underwent 24-hour cuff pressure monitoring under modes I-III, with 19 008 000 monitoring times for each mode. The cuff pressure in mode I was between that in modes II and III [cmH₂O: 27.09 (26.10, 28.14) vs. 26.60 (25.92, 27.47), 31.01 (30.33, 31.88), both P < 0.01]. Moreover, the number of extreme values of cuff pressure > 50 cmH₂O in mode I was significantly lower than that in modes II and III [19 900 cases (0.105%) vs. 22 297 cases (0.117%), 27 618 cases (0.145%), both P < 0.05]. CONCLUSION Dynamically monitoring the CO₂ pressure above the cuff to guide the adjustment of endotracheal tube cuff pressure can achieve better cuff sealing with a relatively lower cuff pressure load.
Humans ; Intubation, Intratracheal/instrumentation* ; Pressure ; Prospective Studies ; Respiration, Artificial ; Male ; Airway Management/methods* ; Female ; Middle Aged

Background Staff in biosafety laboratories (BSL) are more likely to experience occupational burnout and other psychological issues due to their unique working environment and high job demands. However, current research in this field tends to focus on overall analyses, overlooking the internal differences within this group. Objective To explore latent profiles of occupational burnout among BSL workers and their influencing factors, providing a reference for targeted burnout interventions. Methods In 2022, cluster random sampling was used to select 8023 BSL workers in Xinjiang. Data were collected via a questionnaire survey, including a self-designed general information questionnaire, the Maslach Burnout Inventory-General Survey (MBI-GS), and the Effort-Reward Imbalance (ERI) scale, to analyze demographic characteristics, occupational burnout, and job stress status. After data cleaning, latent profile analysis (LPA) was applied to identify burnout profiles, followed by K-means clustering for verification. Logistic regression was used to analyze influencing factors with burnout profiles as the dependent variable. Results After excluding invalid questionnaires, 7924 valid questionnaires were retained, with an recovery rate of 98.77%. The LPA results indicated that occupational burnout among BSL staff was categorized into three latent profiles: a low burnout profile (2208 individuals, 27.86%), a moderate burnout profile (4636 individuals, 58.51%), and a high burnout profile (1080 individuals, 13.63%). A similar grouping was derived from K-means clustering analysis (28.71%, 53.37%, and 17.92%), and a Sankey diagram demonstrated significant overlap between the two classification results. Statistically significant differences were observed across the three latent profiles in all three dimensions of burnout: emotional exhaustion, cynicism, and reduced personal accomplishment. The final logistic regression model revealed that the influencing factors exhibited characteristics of partial overlap and partial differentiation. Among the common influencing factors, the shared protective factors included: age ≥50 years (OR_{moderate burnout}=0.42, OR_{high burnout}=0.45), monthly income of 4000-6000 RMB (OR_{moderate burnout}=0.83, OR_{high burnout}=0.71), good sleep quality (OR_{moderate burnout}=0.70, OR_{high burnout}=0.13) and very good sleep quality (OR_{moderate burnout}=0.51, OR_{high burnout}=0.12), and engaging in physical exercise ≥5 times per week (OR_{moderate burnout}=0.74, OR_{high burnout}=0.48). The protective effects were more pronounced for the high burnout profile. The common risk factors included: 21–30 years of service (OR_{moderate burnout}=1.38, OR_{high burnout}=3.00), ≥31 years of service (OR_{moderate burnout}=1.47, OR_{high burnout}=3.39), working in "other positions" (OR_{moderate burnout}=1.46, OR_{high burnout}=1.56), and occupational stress (ERI>1) (OR_{moderate burnout}=2.62, OR_{high burnout}=3.25), with the risk effects being more significant for the high burnout profile. Regarding differentiated influencing factors, protective factors exclusively associated with the moderate burnout profile included having an associate degree (OR=0.70) and engaging in physical exercise 3-4 times per week (OR=0.74). For the high burnout profile, exclusive protective factors included age 40-50 years (OR=0.56), while exclusive risk factors included having a senior professional title (OR=1.85), holding a managerial role (OR=1.78), a high number of night shifts per month (OR=2.66), and a very high number of night shifts per month (OR=3.93). Conclusion BSL workers exhibit three distinct latent burnout profiles. Occupational burnout requires greater attention, and targeted prevention and intervention strategies should be developed based on worker subtypes.

Objective: To investigate the characteristics of breakthrough cases of varicella in Haishu District, Ningbo City, Zhejiang Province from 2017 to 2022, so as to provide the evidence for varicella prevention and control. Methods: Information on reported cases of varicella and vaccination in Haishu District from 2017 to 2022 were collected through the China Infectious Disease Reporting Management Information System and the Immunization Program Information Management System of Zhejiang Province. The breakthrough cases who had received 1 or 2 doses of varicella vaccine 42 days before the onset of disease were selected. The distribution of sex, age, region and the interval between onset and last immunization were descriptively analyzed. Results: A total of 1 563 varicella cases were reported from 2017 to 2022. There were 928 breakthrough cases (59.37%), of which 660 cases with 1-dose immunization history (42.23%) and 268 cases with 2-dose immunization history (17.15%). The proportion of 1-dose breakthrough cases in total annual cases showed a decreasing trend (P<0.05) from 2017 to 2022, while there was no significant tendency on the proportion of cases with 2-dose immunization history (P>0.05). There were 392 males (59.39%) and 268 females (40.61%) with 1-dose immunization history. There were 150 males (55.97%) and 118 females (44.03%) with 2-dose immunization history. Breakthrough cases with 1- and 2- dose immunization history had an median age of 13.00 (interquartile range, 4.00) and 9.00 (4.00) years, respectively, and the difference was statistically significant (P<0.05). The regional distribution of the breakthrough cases with 1- and 2- dose immunization history was mainly in the rural-urban fringe, with 319 cases (48.33%) and 137 cases (51.12%), respectively, and the difference was statistically significant (P<0.05). The median interval between onset and last immunization was 12.00 (interquartile range, 3.00) and 4.00 (3.00) years, respectively, and the difference was statistically significant (P<0.05). Conclusions The breakthrough cases of varicella in Haishu District from 2017 to 2022 were mainly cases with 1-dose immunization history, males, and residents in rural-urban fringe. The age was older and the interval between onset and the last immunization was longer in cases with 1-dose immunization history than in cases with 2-dose immunization history.

[Objective] To explore the efficacy and safety of retrograde intrarenal surgery (RIRS) using a flexible negative pressure suction sheath in the treatment of upper urinary tract stones >2 cm in diameter, to provide reference for the diagnosis and treatment of such disease. [Methods] Clinical data of 155 patients who underwent surgery for upper urinary tract stones during Nov.2022 and Nov.2023 at the Second Affiliated Hospital of Shaanxi University of Chinese Medicine were retrospectively analyzed.The patients were divided into 3 groups: percutaneous nephrolithotripsy (PCNL) group (n=54), conventional sheath RIRS group (n=41), and flexible sheath RIRS group (n=60). The general and clinical data of the 3 groups were compared. [Results] The PCNL group had more patients with severe hydronephrosis (22.22% vs. 4.88%, 5.00%, P=0.027) and smaller IPA involving the lower calyx [(36.17±17.6)° vs. (48.57±17.56)°, (47.41±10.82)°, P=0.014] than the conventional sheath RIRS group and flexible sheath RIRS group.Three days after operation, the stone-free rate (SFR) was 90.74%, 53.66% and 78.33% in the PCNL, conventional sheath RIRS, and flexible sheath RIRS groups, respectively (P<0.05). At 1 month postoperatively, the SFR was 92.59%, 73.17%, and 81.67%, with no statistically significant difference between the PCNL and flexible sheath RIRS groups (P>0.05), but was higher than that in the conventional sheath RIRS group (P<0.05). The PCNL group had shorter operation time than the two RIRS groups [(65.22±17.67) min vs. (91.73±20.57) min, (94.38±24.75) min, P<0.001], longer postoperative hospital stay [(5.0(4.0, 7.0) d vs.3.0(2.0, 4.0) d, 3.0(2.0, 4.0) d, P<0.001], greater decrease in hemoglobin level [(18.00±5.78) g/L vs. (5.57±5.16) g/L, (7.42±5.09) g/L, P<0.001], and higher visual analogue scale (VAS) score [(4.83±1.48) min vs. (2.95±1.07) min, (3.05±1.21) min, P<0.001], while there was no difference between the two RIRS groups (P>0.05). The costs were lower in the flexible sheath RIRS group than in the conventional sheath RIRS group but higher than in the PCNL group [(23 311.19±1 341.20)yuan vs.(24 550.49±1 172.51)yuan, (15 351.97±1 101.4)yuan, P<0.001]. The overall incidence of complications was similar among the three groups, but stone street occurred only in the conventional sheath RIRS group. [Conclusion] For the treatment of patients with upper urinary tract stones >2 cm, RIRS has shorter postoperative hospital stay, lower hemoglobin decrease, and lower VAS score compared to PCNL; the early postoperative SFR of flexible sheath RIRS is superior to that of conventional sheath RIRS, and the 1-month SFR is comparable to that of PCNL, with a low incidence of stone street.

Purpose/Significance To classify the elderly according to their heterogeneous health status,and to explore the potential categories and influencing factors status,so as to promote the precision of health information services for the elderly.Method/Process Based on the data of the China health and retirement longitudinal study(CHARLS)database in 2018,the elderly are classified according to their health status by the method of latent class analysis,and the main influencing factors are identified by regression analysis.Result/Conclusion The elderly could be divided into 4 categories according to their health status.Age,sex,education level and retirement sta-tus are significant factors affecting the health grouping of the elderly.According to the heterogeneous health characteristics of the elderly,the service optimization strategy should be provided to promote the physical and mental health of the elderly.

Objective:To propose a novel refined subtyping of Neer type Ⅵ proximal humerus fracture-dislocation and explore its clinical application.Methods:A retrospective study was conducted to analyze the data of 36 patients who had been admitted to Department of Orthopaedics, Beijing Friendship Hospital between January 2018 and December 2022 for surgical treatment with proximal humeral internal locking system (PHILOS) for Neer type Ⅵ proximal humerus fracture-dislocation. There were 25 males and 11 females with an age of (46.1±4.7) years. According to the fracture-dislocation and the separation between the humeral head and the stem, the patients with Neer type Ⅵ proximal humerus fracture-dislocation were further subdivided into 3 subtype groups (known as STAB subtypes): subtype-T group (dislocation of the shoulder joint with macro-capitellar fracture, n=14), subtype-A group (proximal humerus fracture-dislocation without separation of the humeral head from the humeral stem, n=12), and subtype-B group (dislocation of the proximal humerus fracture with separation of the humeral head from the humeral stem, n=10). STAB subtyping was performed on the same imaging data from all the patients at admission and 2 weeks later by 4 surgeons with different qualifications. Interobserver and intraobserver agreements of the STAB typing were verified. The operation time, fracture healing time, visual analogue scale (VAS) pain score, Constant-Murley score, and complications were recorded for patients in the 3 subtype groups. Results:The differences in the preoperative general data were not statistically significant between the 3 subtype groups, indicating comparability ( P>0.05). All patients were followed up for (11.2±4.2) months. The inter-observer and intra-observer Kappa values for STAB subtyping were 0.94 and 0.95, respectively. For subtype-T group, subtype-A group, and subtype-B group, respectively, the operation time was (68.9±5.6) min, (90.0±5.2) min, and (113.0±9.2) min; the fracture healing time was (9.0±0.8) weeks, (10.3±1.2) weeks, and (11.8±0.9) weeks; the VAS scores at the last follow-up were 1.0(1.0, 2.0) points, 2.0(1.0, 2.0) points, 2.0(2.0, 3.0) points; the Constant-Murley scores at the last follow-up were (83.6±2.8) points, (74.5±3.0) points, and (62.7±5.5) points. The differences between the 3 subtype groups in the above items were statistically significant ( P<0.05). The overall success rate of closed reduction was 61.1% (22/36). In subtype-T, subtype-A, and subtype-B groups, respectively, the number of patients with successful closed reduction was 13, 7, and 2, while complications occurred in 2, 3, and 6 patients. The differences in closed reduction and complications among the 3 groups were statistically significant ( P<0.05). Conclusions:The STAB subtyping proposed in this study demonstrates strong intra- and inter-group consistency. Because the refined STAB subtyping can reveal differences among all the Neer type Ⅵ proximal humeral fractures and dislocations, it may provide more precise guidance for personalized clinical decision-making.

Objective:To explore the clinical value of syndecan-1 (SDC1), asymmetric dimethylarginine (ADMA) assessment in the early diagnosis and course monitoring of patients with type 2 diabetic kidney disease (DKD).Methods:This is a cross-sectional study. A total of 232 patients with type 2 diabetes admitted to the Department of Endocrinology of Kailuan General Hospital from December 2020 to December 2021 were included. The general biochemical indexes, SDC1 and ADMA were detected. According to urinary albumin/creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR), patients were divided into simple diabetes group (50 cases) and DKD group (182 cases). According to the risk of progression of DKD, the DKD group was further divided into low-progression diabetic nephropathy (LDKD) subgroup (90 cases), medium-progression diabetic nephropathy(MDKD)subgroup (55 cases), and high-progression diabetic nephropathy(HDKD) subgroup (37 cases). Forty healthy people undergoing physical examination during the same period in our hospital were selected as the healthy control group. According to the quartile value of N-acetyl-β-D-glucosaminase/urinary creatinine (NAG/Ucr), the DKD group was divided into Q1- Q4 subgroups, with 45, 45, 46 and 46 cases, respectively. Spearman correlation was used to analyze the correlation between SDC1, ADMA and glomerular and renal tubule injury indexes in DKD patients. Multifactor ordered Logistic regression was used to analyze the influencing factors of the progression risk of DKD and renal tubular injury. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of SDC1 and ADMA for DKD. Results:The levels of systolic blood pressure, diastolic blood pressure, triglyceride (TG), serum creatinine (Scr), uric acid (UA), NAG/Ucr, SDC1 and ADMA in DKD group were higher than those in SDM group and healthy control group (all P<0.05). The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and hemoglobin A1c (HbA 1c) in DKD group were higher than those in healthy control group, and the level of high density lipoprotein cholesterol (HDL-C) was lower than that in healthy control group (all P<0.05). The SDC1 level in HDKD subgroup was higher than that in SDM group and LDKD subgroup, and the ADMA level was higher than that in SDM group and lower than that in LDKD subgroup (all P<0.05). SDC1 level in MDKD subgroup was higher than that in SDM group and LDKD subgroup, ADMA level was higher than that in SDM group, but lower than that in LDKD subgroup (all P<0.05).The levels of SDC1 and ADMA in LDKD subgroup were higher than those in SDM group (all P<0.05). The levels of TC, AporB, HbA 1c, Scr, UACR and SDC1 in NAG/Ucr Q4 subgroup were higher than those in Q1 subgroup, the levels of Scr, UACR and SDC1 were higher than those in Q2 subgroup, and the levels of HbA 1c, Scr, UACR and SDC1 in Q3 subgroup were higher than those in Q1 subgroup (all P<0.05). Spearman correlation analysis showed that SDC1 was positively correlated with UACR, NAG/Ucr ( r=0.757, 0.566, all P<0.05),and was negatively correlated with eGFR ( r=-0.337, P<0.05). ADMA was positively correlated with UACR, NAG/Ucr ( r=0.197, 0.142, all P<0.05). Multifactor ordered Logistic regression analysis showed that SDC1, NAG/Ucr and Scr were the independent influencing factors of progression risk in DKD patients ( OR=2.043, 1.067, 1.047, 0.660, 1.394, all P<0.05), while SDC1, HbA 1c and ACR were the independent influencing factors of renal tubule injury in DKD patients ( OR=1.177, 1.193, 1.002,all P<0.05). ROC curve showed that the area under the curve (AUC) of SDC1 for DKD diagnosis was 0.979, the sensitivity was 92.31%, and the specificity was 92.22%, while the AUC of ADMA for DKD diagnosis was 0.745, the sensitivity was 81.32%, and the specificity was 60.00%. The AUC, sensitivity and specificity of the combined diagnosis of DKD were 0.981, 90.66% and 95.66%. Conclusions:SDC1 is an independent risk factor of DKD progression and tubular injury in DKD patients, which can be used to diagnose early DKD and monitor the progression of DKD. ADMA is suitable for early screening of DKD.

Chondroitin sulfate is an important component of extracellular matrix (ECM) in animal and human body. In recent years, chondroitin sulfate has been proven to have potential efficacy in biomedical application and has been widely used in bone regeneration and osteogenesis, especially in craniofacial reconstruction and dental medicine. Research shows that chondroitin sulfate derivatives and chondroitin sulfate composite scaffolds have great potential in promoting osteogenesis and biomineralization. However, due to the variety of chondroitin sulfate and various application forms, study on its mechanism of osteogenic repair is still insufficient. In this paper, biological characteristics, bone regeneration and osteogenesis of chondroitin sulfate, its application in different biomaterial design and future prospect are discussed.

Objective To investigate the effect of genistein on the proliferation,migration and invasion of prostate cancer cells and its molecular mechanism.Methods Prostate cancer LNCaP and CWR22RV1 cells were divided into the control group(conventional culture)and the experimental group(50μmol/L genistein treatment).The effect of genistein on the proliferation of prostate cancer cells were analyzed by MTT assay.The effect of genistein on the migration and invasion of prostate cancer cells were analyzed by cell scratch assay and Transwell assay.The protein levels of epithelial interstital transformation(EMT)intermediate markers E-Cadherin,N-Cadherin,Vimentin,and tumor stem cell markers CD44 and Oct-4 were detected by Western blot assay.Results MTT assay showed that genistein could inhibit the proliferation of prostate cancer cells.The scratch closure rates of LNCaP and CWR22RV1 cells were significantly reduced in the experimental group compared with those in the control group,and the number of cells passing through the Transwell membrane was significantly reduced(P＜0.05).Western blot assay showed that genistein could down-regulate the expression levels of N-Cadherin,Vimentin,CD44 and Oct4 in prostate cancer cells,and up-regulate the expression of E-Cadherin in epithelial cells(P＜0.01).Conclusion Genistein reduces the dryness of prostate cancer cells by inhibiting the EMT process,thus reducing the proliferation,migration and invasion of prostate cancer cells.