Background In recent years, the increasingly widespread application of nuclear and medical radiation technologies has resulted in a large number of occupational populations exposed to low-dose ionizing radiation (LDIR). At present, there is no consistent conclusion on the effects of long-term exposure to LDIR on the metabolic health of the occupational population. Objective To explore the association between long-term exposure to LDIR and metabolic syndrome (MetS) among medical radiologists. Methods A cross-sectional study was conducted to enroll 6431 medical radiologists who ordered occupational health checkups from January 2022 to December 2023, and basic information such as demographic characteristics, occupational characteristics, lifestyles, and dietary habits was collected through questionnaires. Physical examinations were conducted using a standardized protocol. Individual dose equivalents of occupational external exposure were monitored by dosimeters worn by medical radiologists. Logistic regression model was used for identifying influencing factors of MetS and sensitivity analysis, and restricted cubic spline model was used to explore the dose-response relationship between cumulative effective dose and MetS. Two-stage linear regression was used to evaluate threshold effect of association between cumulative effective dose and MetS. Results The positive rate of MetS was 13.6% (877/6431) among the enrolled 6431 study participants. The logistic regression showed that gender, age, monthly income, body mass index (BMI), cumulative effective dose, and smoking were influencing factors for MetS. The risk of MetS was higher in males (OR=1.511, 95%CI: 1.209, 1.888); using the < 30 years old group as reference, the risk of MetS was higher in the 30-39 years old (OR=1.509, 95%CI: 1.095, 2.079), 40-49 years old (OR=2.214, 95%CI: 1.551, 3.161), and ≥50 years old (OR=3.480, 95%CI: 2.338, 5.181) groups; using the <10000 yuan group as reference, the risk of MetS was lower in the group with a monthly income of 10000-14999 yuan (OR=0.715, 95%CI: 0.582, 0.878); the risk of MetS was higher in the BMI ≥ 24 kg·m⁻² group (OR=7.548, 95%CI: 6.223, 9.156); using the < 0.76 mSv group as reference, the risk of MetS was higher in the cumulative effective dose of 0.76-2.73 mSv group (OR=1.270, 95%CI: 1.017, 1.586); the risk of MetS was higher in the smoking group (OR=1.734, 95%CI: 1.428, 2.107). The results of restricted cubic spline showed that the cumulative effective dose was nonlinearly correlated with MetS (P _{non-linearity}=0.028), with an inflection point of 1.25 mSv. The risk of developing MetS increased by 34.1% for each unit increase in cumulative effective dose up to 1.25 mSv, whereas above 1.25 mSv, the statistical association was not significant. The sensitivity analysis results showed that after excluding the self-reported hypertensive and diabetic patients, the cumulative effective dose 0.76-2.73 mSv group still had an increased risk of developing MetS compared with the < 0.76 mSv group (P < 0.05), and the results were robust. Conclusion Among medical radiologists, male, age, BMI, and smoking are positively correlated with MetS, and monthly income is negatively correlated with MetS; cumulative effective dose is non-linearly correlated with MetS among medical radiologists.

Objective To investigate the epidemiological characteristics of cross-county imported dengue fever cases within Yunnan province in 2023, so as to provide insights into formulation of preventive and control measures for intra-provincial spread of dengue fever. Methods All data pertaining cross-county imported dengue fever cases within Yunnan Province in 2023 were collected, and the temporal, regional and population distributions of the cases were descriptively analyzed. Results A total of 1 664 intra-provincial cross-county imported dengue fever cases were reported in 95 counties (cities, districts) cross 16 profectures (cities) in Yunnan Province in 2023, accounting for 12.34% of total cases in the province. Cross-county imported dengue fever cases were predominantly reported during the period between August and October (1 516 cases, 91.11% of total cases), and peaked in September (659 cases), with a single-day peak on October 8 (36 cases). During the period from September 4 to 10, five counties (cities) with local dengue fever epidemics, including Jinghong City of Xishuangbanna Dai Autonomous Prefecture, Gengma Dai and Wa Autonomous County of Lincang City, Ruili City of Dehong Dai and Jingpo Autonomous Prefecture, Mengla Coun ty of Xishuangbanna Dai Autonomous Prefecture, and Zhenkang County of Lincang City, exported 165 cross-county imported dengue fever cases to the rest of the province. Among the 1 644 intra-provincial cross-county imported dengue fever cases, the male to female ratio was 1.40∶1.00, and 1 329 cases were at ages of 15 to 55 years (79.87%), with farmers as the predominant occupation (886 cases, 53.25%). The top 5 counties (cities/districts) reporting the highest number of intra-provincial cross-county imported dengue fever cases included Simao District (266 cases) and Lancang Lahu Autonomous County (118 cases) of Pu’er City, Mengla County (91 cases) and Menghai County (91 cases) of Xishuangbanna Dai Autonomous Prefecture, and Mangshi City (73 cases) of Dehong Dai and Jingpo Autonomous Prefecture, which accounting for 38.40% of total imported cases. These intra-provincial cross-county imported dengue fever cases originated from 7 counties (cities/districts) in 4 prefectures (cities), including 1 261 cases (76.70%) from Jinghong City of Xishuangbanna Dai Autonomous Prefecture, 224 cases (13.63%) from Ruili City of Dehong Dai and Jingpo Autonomous Prefecture, 103 cases (6.27%) from Gengma Dai and Wa Autonomous County of Lincang City, 31 cases (1.89%) from Mengla County of Xishuangbanna Dai Autonomous Prefecture, 30 cases (1.82%) from Zhenkang County of Lincang City, 10 cases (0.61%) from Cangyuan Wa Autonomous County of Lincang City, and 5 cases (0.30%) from Mohan-Boten Economic Cooperation Zone of Kunming City. In addition, local dengue fever epidemics following intra-provincial cross-county importation of dengue fevers cases in Simao District, Jinggu Dai and Yi Autonomous County, Mangshi City, Longchuan County, and Cangyuan Wa Autonomous County. Conclusions Farmers and students are high-risk populations for intra-provincial cross-county imported dengue fever cases in Yunnan Province, and health education pertaining personal protection against dengue fever should be strengthened among these high-risk populations by governments at all levels. There is a high risk of local out-break of dengue fever following continuous introduction of intra-provincial cross-county imported cases. Standardized management of intra-provincial cross-county imported dengue fever cases should be reinforced to reduce the risk of local epidemics.

OBJECTIVE To systematically evaluate the repair strategies for temporal bone-parotid composite defects,compare the clinical applicability of local muscle flaps and free flaps,and provide references for optimizing the reconstruction of complex head and neck defects.METHODS We retrospectively analyzed the medical records of 17 patients with postoperative defects in the temporal bone-parotid region treated at Beijing Tongren Hospital,Capital Medical University,between January 2018 and June 2023.There were 11 males and 6 females,with a median age of 58 years(range:42-72 years).All patients had undergone radical resection.Defects were reconstructed with local flaps in 13 cases(temporalis muscle flap,n=6;sternocleidomastoid flap,n=3;submental platysma flap,n=2;submental island flap,n=2)and with free flaps in 4 cases(anterolateral thigh fascial flap,n=1;anterolateral thigh flap,n=1;free abdominal adipofascial flap,n=2).RESULTS The primary diseases of the 17 patients were malignant tumors of the external auditory canal and parotid gland(6 cases of squamous cell carcinoma,6 cases of adenoid cystic carcinoma,and 3 cases of ductal carcinoma).All flaps survived completely.One patient with temporalis muscle flap repair developed postoperative wound infection,which healed after debridement and dressing change.The median follow-up period was 16 months(4-29 months).Two cases(11.8%)of external auditory canal squamous cell carcinoma had local recurrence,one case(5.9%)of parotid ductal carcinoma developed pulmonary metastasis 9 months after surgery and died at 15 months.The remaining 14 cases(82.4%)were tumor-free survivors.Functional evaluation showed that the local tissue flap group had a shorter repair time,but was limited by muscle flap rotation arc;the free flap group could accurately match the defect shape,but the surgical time was prolonged to 3.5-4.5 hours.Fourteen cases(82.4%)received postoperative adjuvant radiotherapy.None of the tissue flaps developed radiation necrosis after radiotherapy.CONCLUSION Temporal bone-parotid composite defects need to balance the dual requirements of surgical cavity coverage and cosmetic repair.Local muscle flaps are easy to operate and have reliable blood supply,suitable for small and medium-sized defects;free tissue flaps have better shape adaptability in complex three-dimensional defect reconstruction,but require microsurgical technical support.The repair plan should be comprehensively decided based on the defect range,vascular conditions,and radiotherapy plan.The data of this group confirmed that both techniques can achieve stable therapeutic effects.

Objective:To investigate the sense of coherence, job stressors and mental health status of nurses practitioners, and analyze the correlation among them.Methods:In September 2020, nurses practitioners in Chengdu City, Sichuan Province were selected as the research objects by convenience sampling method. The Sense of Coherence Scale, Nurses' Job Stressors Scale and SCL-90 were used to investigate their sense of coherence, job stressors and mental health status, respectively. Pearson correlation test was used to analyze the correlation among them, and the structural equation model was constructed to explore the mechanism of them.Results:A total of 1693 nurse practitioners were included. The total scores of sense of coherence, job stressors and SCL-90 were (65.00±14.01) points, (69.08±18.38) points and (129.68±52.99) points, respectively. The mean scores of all dimensions of sense of coherence of nurse practitioners were negatively correlated with the mean scores of all dimensions of job stressors and SCL-90 ( P<0.001). And there were positive correlations between the mean scores of all dimensions of job stressors and the mean scores of all dimensions of SCL-90 ( P<0.001). The structural equation model fitted well. The path coefficient between job stressors and sense of coherence was -0.372 ( P<0.001), and the path coefficient between sense of coherence and SCL-90 score was -0.647 ( P<0.001) . Conclusion:The sense of coherence plays a significant buffering role in job stressors and mental health of nurses practitioners. Nursing managers should be committed to improving the level of sense of coherence of nurses, enhance the happiness of nurses at work, and improve their mental health level.

Objective:To investigate the sense of coherence, job stressors and mental health status of nurses practitioners, and analyze the correlation among them.Methods:In September 2020, nurses practitioners in Chengdu City, Sichuan Province were selected as the research objects by convenience sampling method. The Sense of Coherence Scale, Nurses' Job Stressors Scale and SCL-90 were used to investigate their sense of coherence, job stressors and mental health status, respectively. Pearson correlation test was used to analyze the correlation among them, and the structural equation model was constructed to explore the mechanism of them.Results:A total of 1693 nurse practitioners were included. The total scores of sense of coherence, job stressors and SCL-90 were (65.00±14.01) points, (69.08±18.38) points and (129.68±52.99) points, respectively. The mean scores of all dimensions of sense of coherence of nurse practitioners were negatively correlated with the mean scores of all dimensions of job stressors and SCL-90 ( P<0.001). And there were positive correlations between the mean scores of all dimensions of job stressors and the mean scores of all dimensions of SCL-90 ( P<0.001). The structural equation model fitted well. The path coefficient between job stressors and sense of coherence was -0.372 ( P<0.001), and the path coefficient between sense of coherence and SCL-90 score was -0.647 ( P<0.001) . Conclusion:The sense of coherence plays a significant buffering role in job stressors and mental health of nurses practitioners. Nursing managers should be committed to improving the level of sense of coherence of nurses, enhance the happiness of nurses at work, and improve their mental health level.

OBJECTIVE: To screen for small molecular compounds with selective inhibitory activity against cutaneous melanoma cells with BAP1 deletion. METHODS: Cutaneous melanoma cells expressing wild-type BAP1 were selected to construct a BAP1 knockout cell model using CRISPR-Cas9 system, and small molecules with selective inhibitory activity against BAP1 knockout cells were screened from a compound library using MTT assay. Rescue experiment was carried out to determine whether the sensitivity of BAP1 knockout cells to the candidate compounds was directly related to BAP1 deletion. The effects of the candidate compounds on cell cycle and apoptosis were detected with flow cytometry, and the protein expressions in the cells were analyzed with Western blotting. RESULTS: The p53 activator RITA from the compound library was shown to selectively inhibit the viability of BAP1 knockout cells. Overexpression of wild-type BAP1 reversed the sensitivity of BAP1 knockout cells to RITA, while overexpression of the mutant BAP1 (C91S) with inactivated ubiquitinase did not produce any rescue effect. Compared with the control cells expressing wild-type BAP1, BAP1 knockout cells were more sensitive to RITA-induced cell cycle arrest and apoptosis (P < 0.0001) and showed an increased expression of p53 protein, which was further increased by RITA treatment (P < 0.0001). CONCLUSION Loss of BAP1 results in the sensitivity of cutaneous melanoma cells to p53 activator RITA. In melanoma cells, the activity of ubiquitinase in BAP1 is directly related to their sensitivity to RITA. An increased expression of p53 protein induced by BAP1 knockout is probably a key reason for RITA sensitivity of melanoma cells, suggesting the potential of RITA as a targeted therapeutic agent for cutaneous melanoma carrying BAP1-inactivating mutations.
Humans ; Melanoma ; Skin Neoplasms ; Tumor Suppressor Protein p53 ; Apoptosis ; Cell Division ; Tumor Suppressor Proteins/genetics* ; Ubiquitin Thiolesterase/genetics*

OBJECTIVE: To explore whether bortezomib and a Bcl-2 inhibitor exhibit synergistic anti-tumor effect in human acute T lymphoblastic leukemia cells. METHODS: MTT assay was used to determine the cytotoxicity of bortezomib in the absence or presence of Bcl-2 inhibitors (obatoclax, AT-101 and ABT-199) in Jurkat cells. The effects of drug treatment on the expression of Bcl-2 family proteins, LC3B, p62, ubiquitin, BiP/Grp78, p-JNK, p-p38 and CHOP proteins were examined by Western blotting. Flow cytometry was used to determine the effects of bortezomib and Bcl-2 inhibitors (obatoclax, AT-101 and ABT-199) on cell apoptosis. Quantitative real-time PCR was used to measure the mRNA expression levels of the key regulatory factors of unfolded protein reaction (UPR). A zebrafish xenograft model was used to study the anti-tumor effect of bortezomib, obatoclax and their combination in vivo. RESULTS: Bortezomib or Bcl-2 inhibitors alone inhibited the cell viability of Jurkat cells, but only obatoclax and bortezomib showed synergistic cytotoxicity and pro-apoptotic effect. Obatoclax, rather than AT-101 and ABT- 199, blocked autophagic flux in the cells evidenced by concomitant accumulation of LC3B-Ⅱ and p62. Both bortezomib and obatoclax alone caused accumulation of polyubiquinated proteins, and their combination showed a synergistic effect, which was consistent with their synergistic cytotoxicity. The dual blockade of proteasome and autophagy by the combination of bortezomib and obatoclax triggered unfolded protein response followed by cell apoptosis. Preventing UPS dysfunction by tauroursodeoxycholic acid (TUDCA) significantly attenuated the cytotoxicity and pro-apoptotic effect of bortezomib in combination with obatoclax. In zebrafish xenograft models, bortezomib combined with obatoclax significantly decreased tumor foci formation. CONCLUSIONS Bortezomib and obatoclax for dual blockade of protein degradation pathways show synergistic anti-tumor effect in human acute T lymphoblastic leukemia cells.
Antineoplastic Agents ; Apoptosis ; Bortezomib ; Cell Line, Tumor ; Drug Synergism ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Proteolysis ; Proto-Oncogene Proteins c-bcl-2 ; Pyrroles

Objective To evaluate the modifiying efficacy of pectoral nerve ( Pecs) block com-bined with general anesthesia in patients undergoing radical mastectomy. Methods A total of 60 American Society of Anesthesiologists physical status Ⅰ or Ⅱ female patients, aged 40-64 yr, weighing 50-70 kg, scheduled for elective radical mastectomy, were divided into 2 groups ( n= 30 each) using a random num-ber table method: general anesthesia group ( group GA) and Pecs block combined with general anesthesia group ( group PB+GA) . The patients in group PB+GA received Pecs block guided by ultrasound. After the needle was advanced to the pleura plane between the pectoralis major and minor, 0. 33％ ropivacaine 15 ml was injected, and 0. 33％ ropivacaine 30 ml was injected into the surface of the serratus anterior muscle at the level of the third rib. Anesthesia was induced by intravenous injection of midazolam, propofol, sufen-tanil and cisatracurium and maintained by target-controlled infusion of propofol and intermittent intravenous boluses of sufentanil and cisatracurium. Bispectral index value was maintained at 40-60. Patient-controlled intravenous analgesia was performed with sufentanil at the end of surgery. Immediately after anesthesia in-duction, at 30 min and 2 h after skin incision, and at 2, 6 and 24 h after operation, peripheral venous blood samples were collected for determination of the concentrations of plasma epinephrine by radioimmuno-assay, and the blood samples were collected from the end of the finger at the same time for determination of blood glucose concentrations. The consumption of intraoperative sufentanil, emergence time, pressing times of patient-controlled analgesia ( PCA) and development of nausea and vomiting within 24 h after operation were recorded. Results Compared with group GA, blood glucose and plasma epinephrine concentrations were significantly decreased, the intraoperative sufentanil consumption was reduced, the emergence time was shortened, the pressing times of PCA were decreased at 2, 6 and 24 h after operation ( P<0. 05) , and no significant change was found in the incidence of postoperative nausea and vomiting in group PB+GA ( P>0. 05). Conclusion When Pecs block combined with general anesthesia is used in the patients undergoing radical mastectomy, it is helpful in reducing the opioid consumption and more helpful in inhibiting postoper-ative stress responses and pain responses than general anesthesia alone.

Objective To determine the median effective dose (ED50) of oxycodone inhibiting responses to laryngeal mask airway (LMA) insertion when combined with propofol in the adult female patients.Methods Female patients,aged 18-60 yr,with body mass index of 18-24 kg/m2,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective gynecologic surgery,were included.ED50 of oxycodone was determined by up-and-down sequential technique.Anesthesia was induced by target-controlled infusion of propofol at target plasma concentration of 3.0 μg/ml.Oxycodone was injected at the initial dose of 0.11 mg/kg after the target effect-site and plasma concentrations were balanced.LMA was inserted at 5 min following injection.When the response to LMA insertion was positive,the concentration of oxycodone was increased/decreased in the next patient.The difference between the two successive doses was 0.02 mg/kg.LMA insertion response was defined as occurrence of swallowing,biting on the LMA and bucking and/or body movement during insertion.Probit analysis was used to calculate the ED50 and 95％ confidence interval of oxycodone inhibiting responses to LMA insertion when combined with propofol.Results The ED50 (95％ confidence interval) of oxycodone inhibiting responses to LMA insertion was 0.095 (0.080-0.108) mg/kg when combined with propofol.Conclusion The ED50 of oxycodone inhibiting responses to LMA insertion is 0.095 mg/kg when combined with propofol in the adult female patients.

Objective To investigate the safety and effectiveness of different intravenous anesthesia methods for pediatric ERCP . Methods Data of 45 children undergoing ERCP at the Affiliated Hangzhou Hospital of Nanjing Medical University from August 2013 to July 2016, including intravenous anesthesia,the procedure of ERCP, adverse reactions and the waking time were retrospectively studied. Results A total of 45 patients in two groups under intravenous anesthesia successfully underwent ERCP . Seventeen patients ( 37. 8%) whose body weights were over 20 kg and the duration of surgery was predicted less than 30 minutes received deep sedation without airway intubation. Twenty?eight patients ( 62. 2%) with an initial weight of less than 20 kg and the duration of surgery was predicted more than 30 minutes received general anesthesia with airway intubation. In patients with deep sedation, the mean time of waking was 7. 2±6. 3 minutes, body movement reaction occurred in 1 case ( 5. 9%) and with transient decreasing of pulse blood oxygen ( beyond 95%) occurred in 2 cases ( 11. 8%) . In patients receiving endotracheal anesthesia with intubation, the mean waking time was 10. 5±8. 7 minutes without adverse reactions associated with anesthesia. Conclusion Both deep sedation and general anesthesia with airway intubation are safe for pediatric ERCP. However, general anesthesia with airway intubation is an ideal method ensuring the airway safety and oxygen supply for children less than 20 kg undergoing first?time ERCP or the duration of surgery lasting over 30 minutes.