Objective:To construct a biosafety evaluation index system for major emergency public health events in medical institutions.Methods:Based on previous laboratory biosafety evaluation work, relevant regulations and standards on biosafety in China were collected through literature research and expert consultations. Candidate indicators for constructing the biosafety evaluation system for major emergency public health events in medical institutions were selected, and a framework was established. Two rounds of expert questionnaires were conducted to determine the content of the index system based on experts′ evaluation, and each indicator′s relevance and importance were scored. Finally, two rounds of Delphi consultations were carried out, and the Analytic Hierarchy Process (AHP) was applied to calculate the weights of indicators.Results:The response rates for the total four rounds of questionnaire surveys were all 100%. The first two rounds focused on determining the framework, while the latter two focused on determining the weights for each indicator. The authority coefficients of the expert consultations for the two rounds of weights were 0.65 and 0.70, respectively, indicating the reliability of the research results. In the final round of survey, the Kendall′s coefficients of concordance at each level were all greater than 0.1. Through statistical testing, the P-values were all less than 0.05, indicating good coordination of expert opinions. Ultimately, we established an operational biosafety evaluation system for major emergency public health events in medical institutions, consisting of 4 primary indicators, 26 secondary indicators, and 119 tertiary indicators, with additional deduction items, bonus items, unacceptable items, and monitoring indicators.Conclusions:Based on scientific theory, a biosafety evaluation system for major emergency public health events in medical institutions was constructed, achieving the integration of routine and emergency measures. This system can be used for self-assessment of laboratory biosafety during emergency public health events, addressing the lack of unified standards in biosafety evaluation. Through regular self-assessment, it can enhance the level of biosafety management in medical institution laboratories, to realize the value of application and dissemination.

Objective:To investigate the differences in hippocampal subfield volumes and structural covariance network properties among patients with mild cognitive impairment (MCI) exhibiting different cognitive outcomes and normal controls (NCs), and to further evaluate the predictive value of these imaging indicators for cognitive deterioration in MCI patients.Methods:A total of 43 NCs, 65 stable MCI (sMCI), and 26 progressive MCI (pMCI) patients enrolled in the Alzheimer′s Disease Neuroimaging Initiative (ADNI) database between December 2012 and May 2016 were included in this study. Baseline demographic information and T 1-weighted magnetic resonance imaging scans were collected. Hippocampal subfield volumes were extracted using freesurfer software, and structural covariance networks of hippocampal subfields were constructed. Multivariate analysis of covariance was used to compare hippocampal subfield volumes among the 3 groups. A general linear model was applied to examine group differences in hippocampal subfield structural covariance network properties. Least absolute shrinkage and selection operator (LASSO)-Logistic regression was employed to identify imaging predictors associated with conversion to Alzheimer′s disease (AD), based on which structural, network-based, and combined predictive models were constructed. Model discrimination was evaluated using the area under the curve (AUC); internal validation was performed using Bootstrap resampling; model calibration was assessed with the Hosmer-Lemeshow test; and clinical utility was evaluated through decision curve analysis. Results:Significant differences in hippocampal subfield volumes (mm3) were observed among the 3 groups (all P<0.05, Bonferroni-corrected). Specifically, left parasubiculum (65.58±13.30, 61.96±17.56, 49.56±11.82, F=9.900), right parasubiculum (65.92±15.21, 59.45±16.65, 47.69±15.48, F=11.612), left presubiculum (277.09±39.85, 258.15±44.86, 224.05±45.05, F=14.513), right presubiculum (262.85±40.43, 247.41±43.27, 209.97±46.11, F=14.500), left subiculum (399.66±32.19, 374.25±55.83, 306.12±51.62, F=32.923), right subiculum (417.93±48.92, 376.59±51.01, 316.82±70.22, F=28.764), left cornu ammonis 1 (CA1) (592.10±83.87, 561.96±94.72, 490.06±86.89, F=13.352), right CA1 (632.15±100.09, 601.24±88.88, 531.05±110.29, F=10.579), left CA3 (191.58±30.08, 180.47±34.66, 155.08±37.82, F=12.182), right CA3 (210.42±28.92, 203.84±34.80, 176.69±41.47, F=9.597), left CA4 (224.61±28.94, 210.49±35.04, 183.98±36.89, F=16.521), right CA4 (238.49±28.14, 227.43±30.65, 200.23±42.74, F=13.702), left granule cell-molecular layer-dentate gyrus (GC-ML-DG) (259.96±36.76, 239.42±41.17, 207.61±41.84, F=19.831), right GC-ML-DG (273.98±35.12, 258.79±36.82, 227.81±49.07, F=14.204), left molecular layer (505.62±66.16, 468.58±75.17, 402.68±75.47, F=22.293), right molecular layer (527.39±72.39, 493.14±70.39, 423.81±88.09, F=19.588), left hippocampal amygdala transition area (HATA) (54.91±9.99, 49.52±9.93, 43.27±9.59, F=13.571), right HATA (58.43±9.83, 54.55±10.80, 47.12±12.54, F=10.037), left fimbria (69.94±25.04, 56.63±23.74, 40.58±19.83, F=14.846), right fimbria (68.61±26.24, 53.95±23.16, 45.25±17.04, F=10.424), left hippocampal tail (488.37±83.44, 463.54±80.33, 393.83±77.73, F=13.570), and right hippocampal tail (519.78±80.22, 498.84±81.68, 419.75±93.29, F=14.339) all showed significant group differences. Significant group differences were also observed in small-worldness metric γ (0.51±0.10, 0.51±0.08, 0.62±0.14, F=9.317), small-worldness metric λ (0.39±0.02, 0.39±0.02, 0.43±0.04, F=9.925), global efficiency (0.19±0.01, 0.20±0.01, 0.18±0.01, F=3.189), local efficiency (0.26±0.02, 0.26±0.01, 0.27±0.01, F=3.068), clustering coefficient (0.23±0.01, 0.23±0.01, 0.24±0.02, F=4.274), and characteristic path length (0.73±0.06, 0.72±0.06, 0.76±0.07, F=4.477) of the hippocampal subfield structural covariance network (all P<0.05). Specifically, the pMCI group exhibited higher γ ( t=3.773, P<0.001), λ ( t=4.060, P<0.001), local efficiency ( t=2.445, P=0.047), and clustering coefficient ( t=2.849, P=0.015) than the NCs group, and higher γ ( t=4.074, P<0.001), λ ( t=4.068, P<0.001), and characteristic path length ( t=2.986, P=0.010) but lower global efficiency ( t=-2.444, P=0.047) than the sMCI group. The AUC of the structural, network, and combined models based on LASSO-Logistic regression was 0.837, 0.861, and 0.899, respectively. After internal validation, the corrected AUC was 0.835, 0.855, and 0.889, respectively. All models demonstrated good calibration ( P>0.05), and decision curve analysis indicated favorable clinical net benefit across models. Conclusions:Both sMCI and pMCI patients exhibit widespread hippocampal subfield atrophy and altered global properties of hippocampal subfield structural covariance networks compared to NCs. The models constructed based on hippocampal subfield volumes and structural covariance networks show strong potential for predicting cognitive decline in MCI patients.

Objective:To explore associated factors of post-discharge depressive symptom severity in patients with bipolar disorder.Methods:A longitudinal follow-up was conducted to investigate the demographic,behavioral,and clinical characteristics,and social function among discharged patients with bipolar disorder who met the DSM-5 diagnostic criteria.Clinical characteristics were assessed with the Hamilton Depression Scale(HAMD)and Brief Psychiatric Rating Scale(BPRS).Single factor and multivariate regression were carried out to explore the associat-ed factors of depressive symptom severity in patients with bipolar disorder.Results:A total of 298 discharged pa-tients with bipolar disorder were face-to-face interviewed to complete the follow-up survey.At follow-up time,psy-chotic symptoms(standardized(β)=0.18),housework((β)=0.23),social interaction((β)=0.17)and BPRS total score((β)=0.46)were positively associated with HAMD total score.Productive labor and work((β)=-0.27)and person-al life management((β)=-0.15)were negatively associated with HAMD total scores.Conclusion:Post-discharge depressive symptom severity in bipolar disorder patients is influenced by multiple factors.Effective management of psychotic symptoms,combined with enhanced community-based social rehabilitation and functional recovery,may help reduce the persistence or worsening of depressive symptoms and improve prognosis.

Objective:To explore associated factors of post-discharge depressive symptom severity in patients with bipolar disorder.Methods:A longitudinal follow-up was conducted to investigate the demographic,behavioral,and clinical characteristics,and social function among discharged patients with bipolar disorder who met the DSM-5 diagnostic criteria.Clinical characteristics were assessed with the Hamilton Depression Scale(HAMD)and Brief Psychiatric Rating Scale(BPRS).Single factor and multivariate regression were carried out to explore the associat-ed factors of depressive symptom severity in patients with bipolar disorder.Results:A total of 298 discharged pa-tients with bipolar disorder were face-to-face interviewed to complete the follow-up survey.At follow-up time,psy-chotic symptoms(standardized(β)=0.18),housework((β)=0.23),social interaction((β)=0.17)and BPRS total score((β)=0.46)were positively associated with HAMD total score.Productive labor and work((β)=-0.27)and person-al life management((β)=-0.15)were negatively associated with HAMD total scores.Conclusion:Post-discharge depressive symptom severity in bipolar disorder patients is influenced by multiple factors.Effective management of psychotic symptoms,combined with enhanced community-based social rehabilitation and functional recovery,may help reduce the persistence or worsening of depressive symptoms and improve prognosis.

Objective:To construct a biosafety evaluation index system for major emergency public health events in medical institutions.Methods:Based on previous laboratory biosafety evaluation work, relevant regulations and standards on biosafety in China were collected through literature research and expert consultations. Candidate indicators for constructing the biosafety evaluation system for major emergency public health events in medical institutions were selected, and a framework was established. Two rounds of expert questionnaires were conducted to determine the content of the index system based on experts′ evaluation, and each indicator′s relevance and importance were scored. Finally, two rounds of Delphi consultations were carried out, and the Analytic Hierarchy Process (AHP) was applied to calculate the weights of indicators.Results:The response rates for the total four rounds of questionnaire surveys were all 100%. The first two rounds focused on determining the framework, while the latter two focused on determining the weights for each indicator. The authority coefficients of the expert consultations for the two rounds of weights were 0.65 and 0.70, respectively, indicating the reliability of the research results. In the final round of survey, the Kendall′s coefficients of concordance at each level were all greater than 0.1. Through statistical testing, the P-values were all less than 0.05, indicating good coordination of expert opinions. Ultimately, we established an operational biosafety evaluation system for major emergency public health events in medical institutions, consisting of 4 primary indicators, 26 secondary indicators, and 119 tertiary indicators, with additional deduction items, bonus items, unacceptable items, and monitoring indicators.Conclusions:Based on scientific theory, a biosafety evaluation system for major emergency public health events in medical institutions was constructed, achieving the integration of routine and emergency measures. This system can be used for self-assessment of laboratory biosafety during emergency public health events, addressing the lack of unified standards in biosafety evaluation. Through regular self-assessment, it can enhance the level of biosafety management in medical institution laboratories, to realize the value of application and dissemination.

Objective:To investigate the differences in hippocampal subfield volumes and structural covariance network properties among patients with mild cognitive impairment (MCI) exhibiting different cognitive outcomes and normal controls (NCs), and to further evaluate the predictive value of these imaging indicators for cognitive deterioration in MCI patients.Methods:A total of 43 NCs, 65 stable MCI (sMCI), and 26 progressive MCI (pMCI) patients enrolled in the Alzheimer′s Disease Neuroimaging Initiative (ADNI) database between December 2012 and May 2016 were included in this study. Baseline demographic information and T 1-weighted magnetic resonance imaging scans were collected. Hippocampal subfield volumes were extracted using freesurfer software, and structural covariance networks of hippocampal subfields were constructed. Multivariate analysis of covariance was used to compare hippocampal subfield volumes among the 3 groups. A general linear model was applied to examine group differences in hippocampal subfield structural covariance network properties. Least absolute shrinkage and selection operator (LASSO)-Logistic regression was employed to identify imaging predictors associated with conversion to Alzheimer′s disease (AD), based on which structural, network-based, and combined predictive models were constructed. Model discrimination was evaluated using the area under the curve (AUC); internal validation was performed using Bootstrap resampling; model calibration was assessed with the Hosmer-Lemeshow test; and clinical utility was evaluated through decision curve analysis. Results:Significant differences in hippocampal subfield volumes (mm3) were observed among the 3 groups (all P<0.05, Bonferroni-corrected). Specifically, left parasubiculum (65.58±13.30, 61.96±17.56, 49.56±11.82, F=9.900), right parasubiculum (65.92±15.21, 59.45±16.65, 47.69±15.48, F=11.612), left presubiculum (277.09±39.85, 258.15±44.86, 224.05±45.05, F=14.513), right presubiculum (262.85±40.43, 247.41±43.27, 209.97±46.11, F=14.500), left subiculum (399.66±32.19, 374.25±55.83, 306.12±51.62, F=32.923), right subiculum (417.93±48.92, 376.59±51.01, 316.82±70.22, F=28.764), left cornu ammonis 1 (CA1) (592.10±83.87, 561.96±94.72, 490.06±86.89, F=13.352), right CA1 (632.15±100.09, 601.24±88.88, 531.05±110.29, F=10.579), left CA3 (191.58±30.08, 180.47±34.66, 155.08±37.82, F=12.182), right CA3 (210.42±28.92, 203.84±34.80, 176.69±41.47, F=9.597), left CA4 (224.61±28.94, 210.49±35.04, 183.98±36.89, F=16.521), right CA4 (238.49±28.14, 227.43±30.65, 200.23±42.74, F=13.702), left granule cell-molecular layer-dentate gyrus (GC-ML-DG) (259.96±36.76, 239.42±41.17, 207.61±41.84, F=19.831), right GC-ML-DG (273.98±35.12, 258.79±36.82, 227.81±49.07, F=14.204), left molecular layer (505.62±66.16, 468.58±75.17, 402.68±75.47, F=22.293), right molecular layer (527.39±72.39, 493.14±70.39, 423.81±88.09, F=19.588), left hippocampal amygdala transition area (HATA) (54.91±9.99, 49.52±9.93, 43.27±9.59, F=13.571), right HATA (58.43±9.83, 54.55±10.80, 47.12±12.54, F=10.037), left fimbria (69.94±25.04, 56.63±23.74, 40.58±19.83, F=14.846), right fimbria (68.61±26.24, 53.95±23.16, 45.25±17.04, F=10.424), left hippocampal tail (488.37±83.44, 463.54±80.33, 393.83±77.73, F=13.570), and right hippocampal tail (519.78±80.22, 498.84±81.68, 419.75±93.29, F=14.339) all showed significant group differences. Significant group differences were also observed in small-worldness metric γ (0.51±0.10, 0.51±0.08, 0.62±0.14, F=9.317), small-worldness metric λ (0.39±0.02, 0.39±0.02, 0.43±0.04, F=9.925), global efficiency (0.19±0.01, 0.20±0.01, 0.18±0.01, F=3.189), local efficiency (0.26±0.02, 0.26±0.01, 0.27±0.01, F=3.068), clustering coefficient (0.23±0.01, 0.23±0.01, 0.24±0.02, F=4.274), and characteristic path length (0.73±0.06, 0.72±0.06, 0.76±0.07, F=4.477) of the hippocampal subfield structural covariance network (all P<0.05). Specifically, the pMCI group exhibited higher γ ( t=3.773, P<0.001), λ ( t=4.060, P<0.001), local efficiency ( t=2.445, P=0.047), and clustering coefficient ( t=2.849, P=0.015) than the NCs group, and higher γ ( t=4.074, P<0.001), λ ( t=4.068, P<0.001), and characteristic path length ( t=2.986, P=0.010) but lower global efficiency ( t=-2.444, P=0.047) than the sMCI group. The AUC of the structural, network, and combined models based on LASSO-Logistic regression was 0.837, 0.861, and 0.899, respectively. After internal validation, the corrected AUC was 0.835, 0.855, and 0.889, respectively. All models demonstrated good calibration ( P>0.05), and decision curve analysis indicated favorable clinical net benefit across models. Conclusions:Both sMCI and pMCI patients exhibit widespread hippocampal subfield atrophy and altered global properties of hippocampal subfield structural covariance networks compared to NCs. The models constructed based on hippocampal subfield volumes and structural covariance networks show strong potential for predicting cognitive decline in MCI patients.

Objective To explore the clinical values of voxel-based morphometry(VBM)analysis in magnetic resonance imaging(MRI)for detecting secondary damage to the distant thalamus and substantia nigra in patients with cerebral infarction.Methods A total of nineteen patients with first-time unilateral middle cerebral artery(MCA)ischemic stroke were prospectively recruited.Three-dimensional whole-brain MRI scans were performed at 1 week,1 month,and 3 months after onset.VBM analysis was used to analyze changes in the thalamus and substantia nigra volumes.Results VBM analysis revealed that compared to ipsilateral thalamic volume at 1 week after onset,ipsilateral thalamic volume was significantly reduced at 1 month or 3 months after onset(reduced by 637 mm3 and 1488 mm3,respectively;P<0.01),with the atrophy primarily located in the dorsomedial nucleus of the thalamus.Similarly,compared to ipsilateral substantia nigra volume at 1 week after onset,the ipsilateral substantia nigra volume was significantly reduced at 1 month or 3 months after onset(reduced by 64 mm3 and 76 mm3,respectively;P<0.05).Conclusions VBM technology can be used to evaluate the ipsilateral thalamic and substantia nigra volume reduction in patients with cerebral infarction in the MCA supply area at 1-3 months after stroke,and to detect secondary damage.

Objective To investigate the effects of laparoscopic radiofrequency ablation(LRFA)and percutaneous radiofrequency ablation(PRFA)on anti-tumor immunity,complication rate and recurrence rate in patients with primary liver cancer.Methods A total of 81 patients with primary liver cancer treated in Dazhou Central Hospital from January 2020 to August 2022 were selected and divided into observation group(LRFA,n=42)and control group(PRFA,n=39)according to the treatment plan.Compare the total ablation rate,postoperative complication rate,recurrence rate of the two groups,as well as tumor necrosis factor-α(TNF-α),carbohydrate antigen 199(CA199),interleukin-6(IL-6),Golgi protein 73(GP73),C-reactive protein(CRP),alpha-fetoprotein(AFP)and peripheral blood T lymphocyte subpopulation levels before and after surgery.Results There was no significant difference between the observation group(95.24％)and the control group(92.31％)(P＞0.05).At 1 d postoperatively,IL-6 was(124.63±45.41)pg/ml and(168.28±51.26)pg/ml,CRP was(19.14±5.03)ng/L and(28.26±7.47)ng/L,and TNF-α was(94.32±18.49)pg/ml and(108.41±20.11)pg/ml;at 3 d postoperatively,IL-6 was(92.37±24.11)pg/ml and(105.83±27.45)pg/ml in the observation group and the control group,respectively,CRP was(14.87±4.37)ng/L and(17.25±5.06)ng/L,and TNF-α was(75.41±12.10)pg/ml and(82.64±16.83)pg/ml,which were all higher than that of preoperative period(P＜0.05).At 7 d postoperatively,CD3+in the observation group and control group were(66.27±7.82)％and(65.14±7.63)％,AFP was(156.23±30.27)μg/mland(160.84±32.33)μg/ml,GP73 was(65.21±10.26)μg/L and(67.44±11.03)μg/L,CA199 was(44.89±11.41)U/L and(45.12±13.07)U/L,CD4 was(32.02±6.03)％and(31.53±6.11)％,and CD4+/CD8+was(1.31±0.39)and(1.29±0.37)respectively;at 14 d postoperatively,CD3+was(71.25±6.83)％and(70.89±6.76)％,AFP was(48.52±18.31)μg/ml and(50.11±19.12)μg/ml,GP73 was(48.25±8.46)μg/L and(49.12±10.12)μg/L,CA199 was(19.27±5.16)U/L and(20.07±5.39)U/L,and CD4 was(38.25±7.7)U/L and(20.07±5.39)U/L,respectively,in the observation and control groups.g/L,CA199 was(19.27±5.16)U/L and(20.07±5.39)U/L,CD4 was(38.25±7.45)％and(37.61±7.92)％,and CD4+/CD8+was(1.49±0.42)and(1.47±0.45),respectively,which were higher than that of preoperative period(P＜0.05),but the difference between the two groups was not statistically significant(P＞0.05).The postoperative complication rate of 42.86％and recurrence rate of 2.38％in the observation group were lower than 66.67％and 17.95％in the control group(P＜0.05).The 12-month postoperative survival rate of 97.62％in the observation group was not statistically significant compared with 94.87％in the control group(P＞0.05).Conclusion The efficacy of LRFA and PRFA in the treatment of primary hepatocellular carcinoma is comparable,which can effectively improve the body's anti-tumor immunity and reduce the release of serum tumor markers;however,LRFA has less stressful reaction,reduces the occurrence of postoperative complications,and has a lower recurrence rate,which is especially advantageous in the treatment of hepatocellular carcinoma at special sites.

Rheumatoid arthritis (RA) is an autoimmune disease with a complex etiology. Monocyte-derived macrophages (MDMs) infiltration are associated with RA severity. We have reported the deletion of G-protein-coupled receptor kinase 2 (GRK2) reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling. However, as more GRK2-interacting proteins were discovered, the GRK2 interactome mechanisms in RA have been understudied. Thus, in the collagen-induced arthritis mouse model, we performed genetic GRK2 deletion using GRK2^f/fLyz2-Cre^+/- mice. Synovial inflammation and M1 polarization were improved in GRK2^f/fLyz2-Cre^+/- mice. Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptor γ (PPARγ) as a new GRK2-interacting protein. We further confirmed that fms-related tyrosine kinase 1 (Flt-1), which promoted macrophage migration to induce angiogenesis, was inhibited by GRK2-PPARγ signaling. Mechanistically, excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγ ligand-binding domain and enhanced Flt-1 transcription. Furthermore, the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology, Flt-1⁺ macrophages induced-synovial inflammation, and angiogenesis. Altogether, we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling. Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration, affording a distinct way to control joint inflammation and angiogenesis of RA.