Hepatic fibrosis refers to excessive accumulation and abnormal proliferation of fibrous connective tissue in the liver triggered by multiple pathogenic factors， and it may progress to liver cirrhosis， portal hypertension， and liver cancer. The pathological mechanisms of hepatic fibrosis involve hepatocyte injury， inflammatory cell infiltration with the release of inflammatory mediators， hepatic stellate cell activation， and extracellular matrix deposition. Recent studies have focused on mitochondrial dysfunction in disease progression， including the molecular pathways for hepatic fibrosis driven by metabolic disorders， energy deficiency， oxidative stress， mitochondrial dynamic imbalance， and autophagic dysfunction， all of which can induce liver injury. This article reviews the latest advances in hepatic fibrosis， in order to provide new therapeutic strategies for clinical management.

Objective:To investigate the characteristics of brain network reorganization in migraine patients and its relationship with the grading of right-to-left shunt (RLS) in patent foramen ovale(PFO) by integrated 3.0T structural magnetic resonance imaging (MRI),resting-state functional MRI(fMRI),and contrast-enhanced transthoracic echocardiography, thereby toexplore the mechanism underlying cognitive impairment in migraine.Methods:A total of 49 migraine patients (migraine group)and 16 demographically matched healthy subjects (healthy control group) who received diagnosis and treatment at China-Japan Union Hospital of Jilin University from September 2020 to September 2023 were selected as the study participants. Structural images (T1-weighted) and resting-state functional images were obtained from brain imaging (MRI and fMRI) data. The amplitude of low-frequency fluctuation (ALFF) algorithm was used to quantify the intensity of spontaneous neural activity in brain regions, while the Fazekas scale and the Age-Related White Matter Changes (ARWMC) scale were employed to assess white matter lesions. Participants were evaluated using the Mini-Mental State Examination (MMSE). Based on the results of contrast-enhanced transthoracic echocardiography (cTTE),the migraine group was further subdivided into A1 group (18 cases, no PFO), A2 group (17 cases, PFO with small-to-moderate RLS) and A3 group (14 case, PFO with large RLS) group, the differences in brain functional activity and cognitive function were compared among these groups.Results:By Fazekas scale scores and ARWMC scale scores, the incidence of hyperintense foci in the deep white matter regions in the migraine group were higher than those in the healthy control group: 67.3%(33/49) vs. 6/16, 61.2%(30/49) vs. 5/16, there were statistical differences ( P<0.05). Compared with the healthy control group, the migraine group exhibited higher spontaneous neural activity intensity in the brainstem,bilateral posterior cingulate cortex,left medial frontal gyrus,and left middle frontal gyrus,while showing reduced brain activity in the right angular gyrus region. The short-term delayed recall scores and total MMSE scores in the migraine group were lower than thosein the healthy control group: (1.61 ± 1.06) scores vs. (2.44 ± 0.81) scores, (25.06 ± 2.31) scores vs. (27.94 ± 1.44) scores, there were statistical differences ( P<0.05). The short-term delayed recall scores mong the A1 group, A2 group and A3 group had statistical difference( P<0.05). Conclusions:Migraine patients exhibit specific brain functional network reorganization and cognitive dysfunction, which are closely related to the degree of RLS.

Objective:To investigate the characteristics of brain network reorganization in migraine patients and its relationship with the grading of right-to-left shunt (RLS) in patent foramen ovale(PFO) by integrated 3.0T structural magnetic resonance imaging (MRI),resting-state functional MRI(fMRI),and contrast-enhanced transthoracic echocardiography, thereby toexplore the mechanism underlying cognitive impairment in migraine.Methods:A total of 49 migraine patients (migraine group)and 16 demographically matched healthy subjects (healthy control group) who received diagnosis and treatment at China-Japan Union Hospital of Jilin University from September 2020 to September 2023 were selected as the study participants. Structural images (T1-weighted) and resting-state functional images were obtained from brain imaging (MRI and fMRI) data. The amplitude of low-frequency fluctuation (ALFF) algorithm was used to quantify the intensity of spontaneous neural activity in brain regions, while the Fazekas scale and the Age-Related White Matter Changes (ARWMC) scale were employed to assess white matter lesions. Participants were evaluated using the Mini-Mental State Examination (MMSE). Based on the results of contrast-enhanced transthoracic echocardiography (cTTE),the migraine group was further subdivided into A1 group (18 cases, no PFO), A2 group (17 cases, PFO with small-to-moderate RLS) and A3 group (14 case, PFO with large RLS) group, the differences in brain functional activity and cognitive function were compared among these groups.Results:By Fazekas scale scores and ARWMC scale scores, the incidence of hyperintense foci in the deep white matter regions in the migraine group were higher than those in the healthy control group: 67.3%(33/49) vs. 6/16, 61.2%(30/49) vs. 5/16, there were statistical differences ( P<0.05). Compared with the healthy control group, the migraine group exhibited higher spontaneous neural activity intensity in the brainstem,bilateral posterior cingulate cortex,left medial frontal gyrus,and left middle frontal gyrus,while showing reduced brain activity in the right angular gyrus region. The short-term delayed recall scores and total MMSE scores in the migraine group were lower than thosein the healthy control group: (1.61 ± 1.06) scores vs. (2.44 ± 0.81) scores, (25.06 ± 2.31) scores vs. (27.94 ± 1.44) scores, there were statistical differences ( P<0.05). The short-term delayed recall scores mong the A1 group, A2 group and A3 group had statistical difference( P<0.05). Conclusions:Migraine patients exhibit specific brain functional network reorganization and cognitive dysfunction, which are closely related to the degree of RLS.

Objective:To translate and adapt the postoperative recovery in children (PRiC) scale, developing a Chinese version for children undergoing dental treatment under general anesthesia (PRiC-DTGA) with validated psychometric properties.Methods:The PRiC scale underwent forward-backward translation using Brislin′s model. A convenience sample of DTGA patients from the Department of Anesthesiology, School of Stomatology, The Fourth Mility Force Medical University was enrolled for a cross-sectional survey on postoperative complications. Delphi expert consultation informed cultural adaptation based on survey findings to develop the PRiC-DTGA Chinese version. Psychometric validation included reliability and validity testing in a separate DTGA cohort at the same center (April-October 2024).Results:Results from the cross-sectionalsurvey of 231 children showed that 82.7% (191/231) of them hadat least one postoperative complication within 72 hours, and these complications were mainly mild local symptoms. Additionally, 358 copies of the Chinese version of the PRiC-DTGA scale were distributed; 21 invalid questionnaires with incomplete information were excluded, and a total of 337 cases were included inthe study. The final PRiC-DTGA comprised 22 items across three dimensions including physical comfort, social ability, and negative emotional. Exploratory factor analysis (EFA) confirmed all factor loadings>0.4. Confirmatory factor analysis (CFA) demonstrated adequate fit: χ 2/df=1.665, tucker-Lewis index (TLI)=0.924, comparative fit index (CFI)=0.896, standardized root mean square residual (SRMR)=0.041, and root mean square error of approximation (RMSEA)=0.044 (90% CI: 0.035-0.053). Reliability was strong with Cronbach′s α (total scale)=0.853, subscale α=0.632-0.723, split-half reliability=0.824. Validity indices met standards: scale-content validity index (S-CVI)=0.909, Item-CVI range=0.944-1.000, average variance extracted (AVE)=0.473-0.501, composite reliability (CR)=0.830-0.913. Conclusions:The systematically adapted PRiC-DTGA demonstrates robust reliability and validity, serving as an effective tool for assessing postoperative recovery quality in Chinese children following DTGA.

Objective:To investigate the dose characteristics of the Zeiss INTRABEAM system in air and water, providing dose reference for electronic brachytherapy.Methods:A Monte Carlo program was used to establish a three-dimensional model of a miniature X-ray source vacuum drift tube and a 4 cm spherical applicator. The process of electron beam bombardment on a gold target to generate X-rays was simulated, and parameters such as photon fluence spectrum, percentage depth dose, and half-value layer were calculated. Additionally, the radial dose uniformity in water was measured.Results:The average energy of X-rays at 3 cm in air was 20.8 keV, with a half-value layer of 0.08 mm Al. Under the influence of the applicator, the spectrum becomes hardened, with axial and radial average energies of 28.7 and 29.0 keV, respectively. In water, the percentage depth dose (PDD) curve follows an inverse cubic decay with depth, indicating strong dose concentration and rapid fall-off in near-field irradiation. The radial dose uniformity in water exceeded 99.5%.Conclusions:The INTRABEAM device emits low-energy X-rays characterized by shallow penetration depth, and concentrated dose delivery. Its highly uniform dose distribution ensures comprehensive coverage of the target area, making it particularly suitable for treating superficial tumors and for intraoperative radiotherapy at close range.

ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

BACKGROUND: The effects of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment on coronavirus disease 2019 (COVID-19) patients have been preliminarily characterized. However, real-world data on the safety and efficacy of intravenous transfusions of MSCs in hospitalized COVID-19 patients at the convalescent stage remain to be reported. METHODS: This was a single-arm, multicenter, real-word study in which a contemporaneous external control was included as the control group. Besides, severe and critical COVID-19 patients were considered together as the severe group, given the small number of critical patients. For a total of 110 patients, 21 moderate patients and 31 severe patients were enrolled in the MSC treatment group, while 26 moderate patients and 32 severe patients were enrolled in the control group. All patients received standard treatment. The MSC treatment patients additionally received intravenous infusions of MSCs at a dose of 4 × 10 7 cells on days 0, 3, and 6, respectively. The clinical outcomes, including adverse events (AEs), lung lesion proportion on chest computed tomography, pulmonary function, 6-min walking distance (6-MWD), clinical symptoms, and laboratory parameters, were measured on days 28, 90, 180, 270, and 360 during the follow-up visits. RESULTS: In patients with moderate COVID-19, MSC treatment improved pulmonary function parameters, including forced expiratory volume in the first second (FEV1) and maximum forced vital capacity (VCmax) on days 28 (FEV1, 2.75 [2.35, 3.23] vs . 2.11 [1.96, 2.35], P  = 0.008; VCmax, 2.92 [2.55, 3.60] vs . 2.47 [2.18, 2.68], P  = 0.041), 90 (FEV1, 2.93 [2.63, 3.27] vs . 2.38 [2.24, 2.63], P  = 0.017; VCmax, 3.52 [3.02, 3.80] vs . 2.59 [2.45, 3.15], P  = 0.017), and 360 (FEV1, 2.91 [2.75, 3.18] vs . 2.30 [2.16, 2.70], P  = 0.019; VCmax,3.61 [3.35, 3.97] vs . 2.69 [2.56, 3.23], P  = 0.036) compared with the controls. In addition, in severe patients, MSC treatment notably reduced the proportion of ground-glass lesions in the whole lung volume on day 90 ( P  = 0.045) compared with the controls. No difference in the incidence of AEs was observed between the two groups. Similarly, no significant differences were found in the 6-MWD, D-dimer levels, or interleukin-6 concentrations between the MSC and control groups. CONCLUSIONS: Our results demonstrate the safety and potential of MSC treatment for improved lung lesions and pulmonary function in convalescent COVID-19 patients. However, comprehensive and long-term studies are required to confirm the efficacy of MSC treatment. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR2000031430.
Humans ; COVID-19/therapy* ; Female ; Male ; Mesenchymal Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adult ; Umbilical Cord/cytology* ; Mesenchymal Stem Cells/cytology* ; SARS-CoV-2 ; Aged ; Treatment Outcome

Objective:To translate and adapt the postoperative recovery in children (PRiC) scale, developing a Chinese version for children undergoing dental treatment under general anesthesia (PRiC-DTGA) with validated psychometric properties.Methods:The PRiC scale underwent forward-backward translation using Brislin′s model. A convenience sample of DTGA patients from the Department of Anesthesiology, School of Stomatology, The Fourth Mility Force Medical University was enrolled for a cross-sectional survey on postoperative complications. Delphi expert consultation informed cultural adaptation based on survey findings to develop the PRiC-DTGA Chinese version. Psychometric validation included reliability and validity testing in a separate DTGA cohort at the same center (April-October 2024).Results:Results from the cross-sectionalsurvey of 231 children showed that 82.7% (191/231) of them hadat least one postoperative complication within 72 hours, and these complications were mainly mild local symptoms. Additionally, 358 copies of the Chinese version of the PRiC-DTGA scale were distributed; 21 invalid questionnaires with incomplete information were excluded, and a total of 337 cases were included inthe study. The final PRiC-DTGA comprised 22 items across three dimensions including physical comfort, social ability, and negative emotional. Exploratory factor analysis (EFA) confirmed all factor loadings>0.4. Confirmatory factor analysis (CFA) demonstrated adequate fit: χ 2/df=1.665, tucker-Lewis index (TLI)=0.924, comparative fit index (CFI)=0.896, standardized root mean square residual (SRMR)=0.041, and root mean square error of approximation (RMSEA)=0.044 (90% CI: 0.035-0.053). Reliability was strong with Cronbach′s α (total scale)=0.853, subscale α=0.632-0.723, split-half reliability=0.824. Validity indices met standards: scale-content validity index (S-CVI)=0.909, Item-CVI range=0.944-1.000, average variance extracted (AVE)=0.473-0.501, composite reliability (CR)=0.830-0.913. Conclusions:The systematically adapted PRiC-DTGA demonstrates robust reliability and validity, serving as an effective tool for assessing postoperative recovery quality in Chinese children following DTGA.

Objective:To investigate the dose characteristics of the Zeiss INTRABEAM system in air and water, providing dose reference for electronic brachytherapy.Methods:A Monte Carlo program was used to establish a three-dimensional model of a miniature X-ray source vacuum drift tube and a 4 cm spherical applicator. The process of electron beam bombardment on a gold target to generate X-rays was simulated, and parameters such as photon fluence spectrum, percentage depth dose, and half-value layer were calculated. Additionally, the radial dose uniformity in water was measured.Results:The average energy of X-rays at 3 cm in air was 20.8 keV, with a half-value layer of 0.08 mm Al. Under the influence of the applicator, the spectrum becomes hardened, with axial and radial average energies of 28.7 and 29.0 keV, respectively. In water, the percentage depth dose (PDD) curve follows an inverse cubic decay with depth, indicating strong dose concentration and rapid fall-off in near-field irradiation. The radial dose uniformity in water exceeded 99.5%.Conclusions:The INTRABEAM device emits low-energy X-rays characterized by shallow penetration depth, and concentrated dose delivery. Its highly uniform dose distribution ensures comprehensive coverage of the target area, making it particularly suitable for treating superficial tumors and for intraoperative radiotherapy at close range.

Objective To investigate the synergistic therapeutic effects of HER2 antibody-drug conjugate(HER2-ADC)combined with anti-PD-1 antibody(anti-PD-1)on HER2-expressing bladder cancer and elucidate its regulatory mechanisms on the tumor immune microenvironment.Methods Orthotopic tumor models were established in 40 female C57BL/6 mice(6～8 weeks old,body mass 18～22 g)using MB49 bladder cancer cells overexpressing human HER2.When tumors reached 100 mm3,the mice were randomized into(n=10)control(intraperitoneal injection of 1.0 mL PBS),anti-PD-1(200 μg per mouse every 3 d),HER2-ADC(2.5 mg/kg once weekly),and combination groups(same regimens as above monotherapy).Tumor volume and body mass were measured every 3 d during 28-day treatment.Tumor growth kinetics and survival rates were analyzed.Post-treatment survival was monitored until natural death to determine median survival time(n=5).At day 28,blood and tumor samples(n=5)were collected to detect myeloid-derived suppressor cells(MDSCs;CD11b?Gr1?)and regulatory T cells(Tregs;CD4?CD25?FOXP3?)with flow cytometry,tumor-infiltrating CD3?T,CD8?T,and FOXP3?T cells with immunohistochemical assasy,and liver/kidney functions[alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen(BUN),creatinine(CRE)]and tissue damage indicators[lactate dehydrogenase isoenzyme(LDH-L)].Results In 28 d after treatment,the combination group obtained significantly smallest tumor volume than the control group and the 2 monotherapy groups(all P<0.01).The longest median survival was observed in the combination group(65 d,P<0.01),followed by the HER2-ADC group(55 d),anti-PD-1 group(53 d)and control group(41 d).After 28 d of treatment,the combination group exhibited obviously the smallest peripheral proportions of MDSCs/Tregs,most tumor-infiltrating CD3?T/CD8?T cells,and less FOXP3?T cells when compared with the 2 monotherapy groups and control group(all P<0.05).While,the 2 monotherapy groups had smaller MDSCs/Tregs proportions than the control group(P<0.05).No significant differences were observed among the 4 groups in serum ALT,AST,BUN,CRE,or LDH-L levels,and all of them were within normal ranges.Conclusion HER2-ADC combined with anti-PD-1 suppresses the growth of orthotopic bladder tumor,probably through their synergic effects on down-regulating MDSCs/Treg and enhancing CD8?T cell infiltration.