The 3D-printed radiotherapy X-ray dose compensators can significantly improve the spatial accuracy of radiation dose distribution and the homogeneity of the target volume in superficial tumor radiotherapy while reducing the dose to normal tissues by conforming to individual patient surface contours. Their clinical application value is becoming increasingly prominent. However, standardized evaluation systems or technical specifications for such products are currently lacking both domestically and internationally, leading to inconsistent performance assessment and hindering the verification of their clinical safety and effectiveness. To ensure radiotherapy quality and patient health and safety, this study proposed a set of technical specifications for evaluating radiotherapy X-ray dose compensators by reviewing their physical, functional, and safety performance, as well as software and clinical-engineering interaction performance. Furthermore, based on existing technical standards and regulatory review guidelines, quantitative evaluation methods were explored, including computed tomography number calibration phantom testing and dose compensation performance verification. This work aims to provide a scientific reference for future product development, standard formulation, and regulatory review.

Background/Aims: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

Objective:To investigate the incidence of common complications following vaginal delivery and analyze their influencing factors among women of reproductive age.Methods:This prospective cohort study consecutively enrolled women who delivered vaginally at two campuses of the Obstetrics and Gynecology Hospital of Fudan University between February and July 2023. Participants were categorized into groups according to complication occurrence: those with obstetric laceration versus those without, postpartum hemorrhage versus non-hemorrhage, and retained placenta/membranes without hemorrhage vs. non-retention. Data were collected using a self-developed questionnaire on risk factors for vaginal delivery complications. Group comparisons of demographics, obstetric history, intrapartum assessments, and delivery outcomes were performed using Chi-square test (or Fisher's exact test), independent samples t-test, and Mann-Whitney U test. Multivariate logistic regression identified risk factors for the three complication types. Results:Among 1 966 vaginal deliveries, the overall complication rate was 8.1% (159/1 966), with obstetric lacerations representing the most frequent complication at 4.6% (91/1 966), followed by postpartum hemorrhage at 2.7% (53/1 966) and retained placenta/membranes without hemorrhage at 1.4% (27/1 966). Multivariate logistic regression analysis identified distinct sets of independent risk factors for each complication. For obstetric lacerations, adequate gestational weight gain was associated with a reduced risk ( OR=0.547, 95% CI: 0.332-0.900, P=0.018), while precipitous labor ( OR=2.633, 95% CI: 1.321-5.248, P=0.006), shoulder dystocia ( OR=2.495, 95% CI: 1.093-5.691, P=0.030), poor maternal cooperation ( OR=1.887, 95% CI: 1.061-3.359, P=0.031), and specific perineal conditions—particularly reduced skin folds ( OR=2.341, 95% CI: 1.247-4.395, P=0.008) and tight/thick/edematous skin ( OR=2.511, 95% CI: 1.248-5.054, P=0.010)—emerged as significant risk factors. Regarding postpartum hemorrhage, conception through assisted reproductive technology ( OR=3.286, 95% CI: 1.189-9.076, P=0.022), presence of obstetric comorbidities ( OR=2.460, 95% CI: 1.070-5.656, P=0.034), elevated D-dimer levels ( OR=1.157, 95% CI: 1.049-1.277, P=0.004), reduced fibrinogen ( OR=0.521, 95% CI: 0.319-0.851, P=0.009), weak uterine contractions ( OR=20.175, 95% CI: 10.352-39.321, P<0.001), abnormal placentation ( OR=2.434, 95% CI: 1.167-5.078, P=0.018), and absence of early skin-to-skin contact ( OR=0.141, 95% CI: 0.067-0.295, P<0.001) were independently associated with increased risk. For retained placenta/membranes without hemorrhage, prolonged thrombin time ( OR=0.117, 95% CI: 0.034-0.318, P<0.001) and abnormal placentation ( OR=51.843, 95% CI: 14.988-179.324, P<0.001) were identified as primary risk factors. Conclusions:While the overall incidence of complications following vaginal delivery among women of reproductive age is relatively low, high-risk groups warrant particular attention. Precipitous labor, shoulder dystocia, poor maternal cooperation, and unfavorable perineal conditions increase laceration risk. Assisted conception, obstetric comorbidities, elevated D-dimer levels, uterine atony, and placental abnormalities elevate hemorrhage risk. Furthermore, placental abnormalities are strongly associated with retained placenta/membranes without hemorrhage.

Objective:To investigate the correlation between serum NOD-like receptor protein 3 (NLRP3) levels and serum lipids in metabolic-associated fatty liver disease (MAFLD) before and after a single high-fat meal.Methods:A retrospective cohort study was conducted. Sixty-three MAFLD patients (MAFLD group) and fifty-four healthy subjects (CON group) recruited from February 2019 to December 2019 at Hebei Provincial People's Hospital were included. The baseline data were compared between the two groups, and a single high-fat meal trial was conducted. The levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and NLRP3 were measured at 2 h, 4 h, and 6 h after fasting and a high-fat meal. Multiple linear regression analysis was used to evaluate the influencing factors of area under the operating curve (AUC NLRP3) of serum NLRP3 subjects. Logistic regression analysis was used to evaluate the correlation between serum AUC NLRP3 and the risk of MAFLD. Results:The levels of TC, TG, LDL-C, and NLRP3 were significantly higher in the fasting group than the CON group at 2 h, 4 h, and 6 h after a meal [TC (mmol/L), fasting: (5.29±1.01) vs. (4.28±0.62), 2 h: (5.24±0.98) vs. (4.25±0.62), 4 h: (5.38±1.04) vs. (4.26±0.63), 6 h: (5.54±1.07) vs. (4.41±0.65); TG (mmol/L), fasting: (2.67±0.96) vs. (0.92±0.33), 2 h: (3.91±1.35) vs. (1.69±0.59), 4 h: (5.09±1.7) vs. (1.91±0.93), 6 h: (5.36±2.27) vs. (1.75±1.03); LDL-C (mmol/L), fasting: (3.47±0.74) vs. (2.65±0.49), 2 h: (3.36±0.71) vs. (2.58±0.49), 4 h: (3.30±0.71) vs. (2.55±0.47), 6 h: (3.36±0.74) vs. (2.63±0.48); NLRP3 (ng/L), fasting: (84.63±12.96) vs. (56.71±11.37), 2 h: (106.06±17.76) vs. (69.12±14.92), 4 h: (89.78±15.98) vs. (57.74±12.34), 6 h: (80.03±13.61) vs. (54.06±10.35); P<0.001], while the HDL-C level was significantly lower than the CON group [HDL-C (mmol/L), fasting: (1.14±0.24) vs. (1.33±0.29), 2 h: (1.14±0.24) vs. (1.33±0.29), 4 h: (1.09±0.24) vs. (1.27±0.28), and 6 h: (1.05±0.26) vs. (1.29±0.30); P<0.001]. Serum AUC NLRP3 was significantly correlated with AUC TG and AUC LDL-C (AUC TG: B=7.391, 95% CI:5.662-9.12; AUC LDL-C: B=6.559, 95% CI:3.052-10.065; P<0.001) after adjusting for confounding factors, and it was identified as an independent influencing factor for MAFLD ( OR=1.039, 95% CI:1.007-1.071; P=0.015). Conclusion:The serum NLRP3 levels before and after a single high-fat meal are significantly associated with elevated TG and LDL-C levels, and may influence the progression of MAFLD.

Background As a pillar industry in China, the manufacturing sector has a high incidence of non-fatal occupational injuries. The factors influencing non-fatal occupational injuries in this industry are closely related at various levels, including individual, equipment, environment, and management, making the analysis of these influencing factors complex. Objective To identify influencing factors of non-fatal occupational injuries among manufacturing workers, providing a basis for targeted interventions and surveillance. Methods A total of 2243 frontline workers from cable and shipbuilding enterprises were selected as study subjects to investigate the incidence of non-fatal occupational injuries and collect information at four levels: individual, equipment, management, and environment in past 12 months. Data balancing was performed using resampling, and LASSO regression was used to select factors of non-fatal occupational injuries. The influence degree and type of variables were judged based on the magnitude of the estimated coefficients of each variable, where variables with estimated coefficients > 0 are risk factors, and those <0 are protective factors. The area under the receiver operating characteristic (ROC)curve (AUC) was used to test the performance of the model, with an AUC value > 0.7 indicating good model performance. Results Among the 2243 frontline workers, males accounted for 77.7% (1742 out of 2243), with the main age range being 40-49 years old, representing 29.5% (661 out of 2243), 82.7% of the workers (1854 out of 2243) were married, and 55.6% (1248 out of 2243) had a junior middle school education level. The average monthly income for 51.0% (1144 out of 2243) of the workers was between 5000 and 6999 Chinese Yuan. The incidence of non-fatal occupational injuries among the manufacturing workers was 8.4% (189/2243) in the past 12 months. Among the 22 factors associated with the occurrence of non-fatal occupational injuries (P<0.05), 10 were individual-level factors, including gender, smoking, alcohol consumption, colleague relationships, average exercise duration, job burnout, work fatigue, musculoskeletal disorders, cardiovascular diseases, and neurological and sensory organ diseases; 3 were equipment-level factors, including equipment operability, hazardous workpieces, and safety hazards; 5 were environmental-level factors, including low temperatures, special operations, noise, workspace size, and dirty and disorderly environment; and 4 were management-level factors, including daily working hours, weekly working days, overtime, and pre-job technical training. The AUC value of the LASSO regression model was 0.704 and the final model retained a total of 10 variables. Among them, there were 7 risk factors for non-fatal occupational injuries (coefficient > 0), including safety hazards, musculoskeletal disorders, dangerous workpieces, job burnout, dirty and disorderly environment, smoking, and male gender; and 3 protective factors (coefficient < 0), including pre-job technical training, good colleague relationship, and long working days per week. Conclusion Manufacturing enterprises need to focus on the incidence of non-fatal occupational injuries and conduct targeted interventions for non-fatal occupational injuries by controlling potential safety hazards, providing pre-job technical training, reducing dangerous workpieces, rectifying working environment, and reasonably arranging working hours.

G protein-coupled receptor kinase 2 (GRK2) participates in the phosphorylation and desensitization of G protein-coupled receptor (GPCR), impacting various biological processes such as inflammation and cell proliferation. Dysregulated expression and activity of GRK2 have been reported in multiple cells in rheumatoid arthritis (RA). However, whether and how GRK2 regulates synovial hyperplasia and fibroblast-like synoviocytes (FLSs) proliferation is poorly understood. In this study, we investigated the regulation of GRK2 and its biological function in RA. We found that GRK2 transmembrane activity was increased in FLSs of RA patients and collagen-induced arthritis (CIA) rats. Additionally, we noted a positive correlation between high GRK2 expression on the cell membrane and serological markers associated with RA and CIA. Immunoprecipitation-mass spectrometry and pull-down analyses revealed tumor necrosis factor receptor-associated factor 2 (TRAF2) as a novel substrate of GRK2. Furthermore, surface plasmon resonance (SPR) and molecular docking assays determined that the C-terminus of GRK2 binds to the C-terminus of TRAF2 at the Gln340 residue. GRK2 knockdown and the GRK2 inhibitor CP-25 attenuated synovial hyperplasia and FLS proliferation in CIA both in vitro and in vivo by decreasing GRK2 membrane expression and activity. Mechanistically, increased GRK2 transmembrane activity contributed to the recruitment of TRAF2 on the cell membrane, promoting GRK2-TRAF2 interactions that facilitate the recruitment of the E3 ubiquitin ligase TRIM47 to TRAF2. This enhanced TRAF2 Lys63 polyubiquitylation and induced nuclear factor (NF)-κB activation, leading to synovial hyperplasia and abnormal proliferation of FLSs. Our study provides a mechanistic and preclinical rationale for further evaluation of GRK2 as a therapeutic target for RA.

Objective:To investigate the incidence of common complications following vaginal delivery and analyze their influencing factors among women of reproductive age.Methods:This prospective cohort study consecutively enrolled women who delivered vaginally at two campuses of the Obstetrics and Gynecology Hospital of Fudan University between February and July 2023. Participants were categorized into groups according to complication occurrence: those with obstetric laceration versus those without, postpartum hemorrhage versus non-hemorrhage, and retained placenta/membranes without hemorrhage vs. non-retention. Data were collected using a self-developed questionnaire on risk factors for vaginal delivery complications. Group comparisons of demographics, obstetric history, intrapartum assessments, and delivery outcomes were performed using Chi-square test (or Fisher's exact test), independent samples t-test, and Mann-Whitney U test. Multivariate logistic regression identified risk factors for the three complication types. Results:Among 1 966 vaginal deliveries, the overall complication rate was 8.1% (159/1 966), with obstetric lacerations representing the most frequent complication at 4.6% (91/1 966), followed by postpartum hemorrhage at 2.7% (53/1 966) and retained placenta/membranes without hemorrhage at 1.4% (27/1 966). Multivariate logistic regression analysis identified distinct sets of independent risk factors for each complication. For obstetric lacerations, adequate gestational weight gain was associated with a reduced risk ( OR=0.547, 95% CI: 0.332-0.900, P=0.018), while precipitous labor ( OR=2.633, 95% CI: 1.321-5.248, P=0.006), shoulder dystocia ( OR=2.495, 95% CI: 1.093-5.691, P=0.030), poor maternal cooperation ( OR=1.887, 95% CI: 1.061-3.359, P=0.031), and specific perineal conditions—particularly reduced skin folds ( OR=2.341, 95% CI: 1.247-4.395, P=0.008) and tight/thick/edematous skin ( OR=2.511, 95% CI: 1.248-5.054, P=0.010)—emerged as significant risk factors. Regarding postpartum hemorrhage, conception through assisted reproductive technology ( OR=3.286, 95% CI: 1.189-9.076, P=0.022), presence of obstetric comorbidities ( OR=2.460, 95% CI: 1.070-5.656, P=0.034), elevated D-dimer levels ( OR=1.157, 95% CI: 1.049-1.277, P=0.004), reduced fibrinogen ( OR=0.521, 95% CI: 0.319-0.851, P=0.009), weak uterine contractions ( OR=20.175, 95% CI: 10.352-39.321, P<0.001), abnormal placentation ( OR=2.434, 95% CI: 1.167-5.078, P=0.018), and absence of early skin-to-skin contact ( OR=0.141, 95% CI: 0.067-0.295, P<0.001) were independently associated with increased risk. For retained placenta/membranes without hemorrhage, prolonged thrombin time ( OR=0.117, 95% CI: 0.034-0.318, P<0.001) and abnormal placentation ( OR=51.843, 95% CI: 14.988-179.324, P<0.001) were identified as primary risk factors. Conclusions:While the overall incidence of complications following vaginal delivery among women of reproductive age is relatively low, high-risk groups warrant particular attention. Precipitous labor, shoulder dystocia, poor maternal cooperation, and unfavorable perineal conditions increase laceration risk. Assisted conception, obstetric comorbidities, elevated D-dimer levels, uterine atony, and placental abnormalities elevate hemorrhage risk. Furthermore, placental abnormalities are strongly associated with retained placenta/membranes without hemorrhage.

Objective:To investigate the correlation between serum NOD-like receptor protein 3 (NLRP3) levels and serum lipids in metabolic-associated fatty liver disease (MAFLD) before and after a single high-fat meal.Methods:A retrospective cohort study was conducted. Sixty-three MAFLD patients (MAFLD group) and fifty-four healthy subjects (CON group) recruited from February 2019 to December 2019 at Hebei Provincial People's Hospital were included. The baseline data were compared between the two groups, and a single high-fat meal trial was conducted. The levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and NLRP3 were measured at 2 h, 4 h, and 6 h after fasting and a high-fat meal. Multiple linear regression analysis was used to evaluate the influencing factors of area under the operating curve (AUC NLRP3) of serum NLRP3 subjects. Logistic regression analysis was used to evaluate the correlation between serum AUC NLRP3 and the risk of MAFLD. Results:The levels of TC, TG, LDL-C, and NLRP3 were significantly higher in the fasting group than the CON group at 2 h, 4 h, and 6 h after a meal [TC (mmol/L), fasting: (5.29±1.01) vs. (4.28±0.62), 2 h: (5.24±0.98) vs. (4.25±0.62), 4 h: (5.38±1.04) vs. (4.26±0.63), 6 h: (5.54±1.07) vs. (4.41±0.65); TG (mmol/L), fasting: (2.67±0.96) vs. (0.92±0.33), 2 h: (3.91±1.35) vs. (1.69±0.59), 4 h: (5.09±1.7) vs. (1.91±0.93), 6 h: (5.36±2.27) vs. (1.75±1.03); LDL-C (mmol/L), fasting: (3.47±0.74) vs. (2.65±0.49), 2 h: (3.36±0.71) vs. (2.58±0.49), 4 h: (3.30±0.71) vs. (2.55±0.47), 6 h: (3.36±0.74) vs. (2.63±0.48); NLRP3 (ng/L), fasting: (84.63±12.96) vs. (56.71±11.37), 2 h: (106.06±17.76) vs. (69.12±14.92), 4 h: (89.78±15.98) vs. (57.74±12.34), 6 h: (80.03±13.61) vs. (54.06±10.35); P<0.001], while the HDL-C level was significantly lower than the CON group [HDL-C (mmol/L), fasting: (1.14±0.24) vs. (1.33±0.29), 2 h: (1.14±0.24) vs. (1.33±0.29), 4 h: (1.09±0.24) vs. (1.27±0.28), and 6 h: (1.05±0.26) vs. (1.29±0.30); P<0.001]. Serum AUC NLRP3 was significantly correlated with AUC TG and AUC LDL-C (AUC TG: B=7.391, 95% CI:5.662-9.12; AUC LDL-C: B=6.559, 95% CI:3.052-10.065; P<0.001) after adjusting for confounding factors, and it was identified as an independent influencing factor for MAFLD ( OR=1.039, 95% CI:1.007-1.071; P=0.015). Conclusion:The serum NLRP3 levels before and after a single high-fat meal are significantly associated with elevated TG and LDL-C levels, and may influence the progression of MAFLD.

Objective:To provide basis for preventing flight safety accidents caused by hypoxia by exploring the subjective and objective performance of pilots in hypobaric hypoxia environment.Methods:The relevant data of pilots′ high altitude physiological training were retrospectively analyzed and a symptom questionnaire upon the training were summarized. The pilots were divided into excellent group (time of useful consciousness >6 min), good group (3 min ≤time of useful consciousness <6 min) and qualified group (2 min ≤time of useful consciousness <3 min) according to the time of useful consciousness. The hypoxia symptoms and physiological parameters of pilots in each group were statistically analyzed.Results:A total of 919 pilots were included, in which 416 were in excellent group, 490 were in good group and 13 were in qualified group. Among the 25 hypoxia symptoms, there were significant differences in the components of numbness and difficulty in calculation among 3 groups ( χ2=6.04, 7.79, P=0.049, 0.020), but there were no significant differences in the components of the other 23 hypoxia symptoms (all P>0.05). The changes of blood oxygen saturation were significant in group main effect, time main effect and their interaction ( F=25.65, 1 039.77, 25.22, all P<0.001). The change of heart rate was statistically significant in the main effect of time ( F=66.41, P<0.001) but in time main effect and their interaction (both P>0.05). There was no significant difference in respiratory rate among group main effect, time main effect and their interaction (all P>0.05). The distribution and variation of blood oxygen saturation were statistically significant differences among the 3 groups in the ranges of 81%-90%, 71%-80% and 65%-70% ( H=125.93, 372.83, 13.10, all P≤0.001) unlike the range of 91%-100% ( H=2.48, P=0.289). Conclusions:The excellent group showed better blood oxygen saturation maintaining and useful consciousness time enduring capabilities, and those imply them in better performance and consciousness that enable the operation in hypoxic environment with more ease.

Objective:To provide scientific basis for pilots′ hypoxia training by comparing and analyzing the effects of hypoxia training under normobaric and hypobaric environments.Methods:Forty-two healthy subjects were selected. The pilot reduced oxygen breathing device and hypobaric chamber were used to simulate 7 500 m hypoxia training, and blood oxygen saturation, heart rate, respiratory rate and hypoxia endurance time were monitored and recorded. The hypoxia symptom questionnaire was filled out by the subjects after 2 training sessions. The hypoxia endurance time and hypoxia tolerance grade of normobaric and hypobaric hypoxia training were analyzed, and the differences of blood oxygen saturation and hypoxia symptoms were compared between 2 hypoxia trainings.Results:Forty-two subjects completed the normobaric and hypobaric hypoxia trainings. The survival curve analysis of hypoxia endurance time showed that the median hypoxia endurance time of normobaric and hypobaric hypoxia training was [3.17(2.70, 3.64)] min and [3.67(3.46, 3.88)] min respectively, with no significant difference ( P>0.05). There was no significant difference in the grade distribution of hypoxia tolerance between 2 hypoxia trainings ( P>0.05). The blood oxygen saturation curves of 2 hypoxia trainings were basically consistent. There was no significant difference between 2 hypoxia trainings on blood oxygen saturation, heart rate and respiratory rate (all P>0.05). There were significant differences in difficulty in calculation, difficulty in concentration and with palpitation ( χ2=4.81, 3.97, 3.98, P=0.028, 0.046, 0.046). Conclusions:The analysis showed that most physiological responses and subjective symptoms of pilots are quite similar in the normobaric and hypobaric hypoxia training at simulated 7 500 m. Both normobaric and hypobaric exposures show the similar hypoxia training effect.