ObjectiveTo investigate the mechanism of Guizhi Fulingwan （GFW） against hepatic fibrosis， focusing on elucidating the regulatory effect of GFW on the mitochondrial DNA （mtDNA）/NOD-like receptor protein 3 （NLRP3）/cysteinyl aspartate-specific proteinase-1 （Caspase-1）/gasdermin D （GSDMD） signaling pathway. MethodsForty-two male Sprague-Dawley （SD） rats were randomly allocated into six groups （n=7）： control， model， low/medium/high-dose （0.14， 0.28， 0.56 g·kg^-1·d^-1） GFW （GFW-L， GFW-M， GFW-H）， and Dahuang Zhechong pills （DZW， 1.8 g·kg^-1·d^-1）. The rat model of hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride. General conditions of the rats were observed. Serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured. Liver histopathology and collagen deposition were observed through hematoxylin and eosin （HE） staining and Masson's trichrome staining. Transmission electron microscopy （TEM） was employed to observe structural alterations and damage of cellular ultrastructures including mitochondria. Mitochondrial membrane potential （MMP， ΔΨ_m） was detected by flow cytometry. Serum levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were measured by enzyme-linked immunosorbent assay （ELISA）. The mRNA levels of mtDNA and NLRP3 in the liver tissue were quantified by Real-time polymerase chain reaction （Real-time PCR）. The protein levels of key molecules in the NLRP3/Caspase-1/GSDMD signaling pathway in the liver tissue were determined by Western blot. ResultsCompared with the control group， the model group exhibited a decrease in body weight （P<0.01）， an increase in liver index （P<0.01）， elevations in serum ALT and AST levels （P<0.01）， and typical fibrotic features such as disorganized hepatocytes， inflammatory infiltration， and increased collagen deposition in the liver tissue. TEM revealed significant karyotheca degeneration， mitochondrial swelling， endoplasmic reticulum expansion， and organelle efflux in the model group. In addition， the model group showed decreased ΔΨ_m （P<0.01）， up-regulated mRNA levels of mtDNA and NLRP3 （P<0.01） and protein levels of NLRP3， Caspase-1， and GSDMD （P<0.01） in the liver tissue， and increased serum levels of IL-1β and IL-18 （P<0.01）. Compared with that in the model group， the body weight increased in GFW-L， GFW-M， and DZW groups （P<0.05） and markedly increased in the GFW-H group （P<0.01）. The liver index decreased in the GFW groups and DZW group （P<0.01）. The serum ALT level declined in the GFW-L group （P<0.05）， and the serum ALT and AST levels decreased in the GFW-M， GFW-H， and DZW groups （P<0.01）. Histopathological damage and fibrosis were alleviated to varying degrees， and TEM revealed mitigated ultrastructural injuries including mitophagy， mitochondrial swelling， and endoplasmic reticulum expansion in the drug intervention groups. The ΔΨ_m increased in GFW groups without statistical significance. The mRNA level of mtDNA in the liver tissue was down-regulated in the GFW-M （P<0.05）， GFW-H （P<0.01）， and DZW （P<0.01） groups. The mRNA level of NLRP3 was down-regulated in GFW-M， GFW-H， and DZW groups （P<0.01）. Western blot analysis showed significantly down-regulated protein level of NLRP3 in all the GFW groups and the DZW group （P<0.01）. The protein level of GSDMD-N was down-regulated in GFW-H and DZW groups （P<0.01）. The protein level of cleaved Caspase-1 was down-regulated in GFW-M （P<0.05）， GFW-H （P<0.01）， and DZW （P<0.01） groups. In addition， the serum levels of IL-1β and IL-18 declined in GFW-H and DZW groups （P<0.01）. ConclusionGFW can suppress pyroptosis to ameliorate CCl₄-induced hepatic fibrosis， potentially through mitigating mitochondrial damage， inhibiting inflammasome assembly and activation， and blocking pro-inflammatory cytokine release.

Depression is a common mental disorder in clinical practice， and it falls under the category of depression syndrome in traditional Chinese medicine （TCM）. In TCM， Qi depression is considered as the root cause of all depression syndromes. Qi depression can lead to blood stasis， which is a key cause of diseases due to depression syndrome. Therefore， treating stasis is an important therapeutic approach for depression syndrome. Salviae Miltiorrhizae Radix et Rhizoma， a representative herbal medicine for activating blood and removing stasis， is effective in activating blood， removing stasis， dredging meridians， and alleviating pain. Currently， it is primarily used in clinical practice to treat cardiovascular and cerebrovascular diseases， such as neurasthenia， coronary heart disease， insomnia， and palpitations. The active components of Salviae Miltiorrhizae Radix et Rhizoma are complex and exhibit a variety of pharmacological effects. These components include water-soluble salvianolic acids and lipid-soluble tanshinones. Modern pharmacological studies have proven that Salviae Miltiorrhizae Radix et Rhizoma and its active components possess antioxidant， anti-inflammatory， anti-tumor， anti-fibrosis， and neuroprotective properties. In recent years， increasing attention has been paid to the pharmacological effects and mechanisms of Salviae Miltiorrhizae Radix et Rhizoma and its active components in treating depression. This paper systematically reviews the antidepressant mechanisms of Salviae Miltiorrhizae Radix et Rhizoma and its main active components from the regulation of monoamine neurotransmitters， the hypothalamic-pituitary-adrenal axis， neurotrophic factors， and neuroinflammation. In addition， this paper summarizes the clinical applications of the prescriptions containing Salviae Miltiorrhizae Radix et Rhizoma in the treatment of depression， providing new insights for further research on the pharmacological mechanisms of Salviae Miltiorrhizae Radix et Rhizoma in treating depression.

BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

Objective To investigate the clinical value of tumor-stroma ratio (TSR) in combination with KRAS, BRAF, NRAS, and microsatellite status for prognostic assessment of patients with colorectal cancer. Methods A total of 51 colorectal cancer cases meeting the inclusion and exclusion criteria were enrolled in this study. TSR levels were evaluated through optical microscopy. The KRAS/NRAS/BRAF mutation profiles and microsatellite status were determined in accordance with genetic testing results. Clinical data, pathological characteristics, and survival outcomes were systematically recorded. Results Among the 51 patients with colorectal cancer, 19 (37.3%) were categorized into the low stromal group and 32 (62.7%) into the high stromal group. Statistically significant differences were observed between the two groups in drug resistance, M stage, TNM stage, neural invasion, and microsatellite status (P<0.05). Compared with patients exhibiting high TSR, those with low TSR demonstrated significantly increased recurrence rates (5 vs. 21 cases, P=0.007), shortened disease-free survival (34.21 vs. 14.34 months, P=0.001), and reduced overall survival (38.79 vs. 23.09 months, P=0.021). Multivariate Cox regression analysis identified N stage, M stage, TNM stage, neural invasion, lymphovascular invasion, and TSR as independent risk factors for disease-free survival. N stage, M stage, neural invasion, lymphovascular invasion, and TSR emerged as independent prognostic factors for overall survival (P<0.05). Although the combined models of TSR with KRAS, NRAS, BRAF, and microsatellite status, respectively, demonstrated overall statistical significance (P<0.05), none of the dummy variables in these models reached individually statistical significance (P>0.05), and therefore cannot be considered independent prognostic factors. Conclusion TSR serves as an independent predictor of poor prognosis in advanced colorectal cancer, with patients exhibiting low TSR demonstrating a significantly higher risk of recurrence and metastasis than those with high TSR. For patients with colon cancer undergoing first-line palliative chemotherapy after postoperative recurrence, histopathological assessment of TSR in primary tumor sites holds prognostic value and may serve as a relevant factor for evaluating treatment resistance in clinical management.

Objective:To analyze the color Doppler flow imaging (CDFI) features of familial exudative vitreoretinopathy (FEVR) at different stages.Methods:A retrospective study. A total of 104 patients with 201 eyes from Department of Ophthalmology of Beijing Tongren Hospital who were hospitalized for fundus examination and diagnosed with FEVR from 2018 to 2022 were included. There were 69 male cases with 133 eyes and 35 female cases with 68 eyes. The age was ranged from 2 months to 11 years, with a mean age of 2.9 years. Fundus and CDFI examination were performed in both eyes. Fluorescein fundus angiography was performed in 72 cases (144 eyes). FEVR staging was conducted according to literature standards. The presence of avascular areas in the peripheral retina or abnormal retina neovascularization was stage 1; the presence of retinal neovascularization at the vitreoretinal interface in the avascular area was stage 2; partial retinal detachment without macula involvement was stage 3; partial retinal detachment involving the macula was stage 4; complete retinal detachment was stage 5. The CDFI ultrasound features of FEVR at different stages were analyzed. The CDFI image features of FEVR patients in different stages were observed.Results:Among the 104 patients, 97 (93.3%, 97/104) cases were binocular and 7 (6.7%, 7/104) cases were monocular. In 201 eyes, stages 1 to 5 of FEVR were 49 (24.4%, 49/201), 23 (11.4%, 23/201), 39 (19.4%, 39/201), 71 (35.3%, 71/201), and 19 (9.5%, 19/201) eyes, respectively. CDFI examination showed no abnormality or mild vitreous opacity in 49 eyes vitreous body at stage 1. Vitreous opacities were observed in all 23 eyes in stage 2, and the echo of the temporal ballwall was not smooth. In 39 eyes at stage 3, the anterior globular cluster echo in temporal peripheral eyes was observed in 17 eyes and partial retinal detachment was observed in 13 eyes. In 71 eyes at stage 4, 51 eyes had temporal or infratemporal retinal folds, and 20 eyes had temporal retinal detachment. All the 19 eyes in stage 5 had total retinal detachment, of which 15 eyes had closed "funnel-shaped" retinal detachment. Among the patients with retinal folds, 13 had bilateral folds, and the fellow eyes of the other 25 patients with unilateral folds all had vitreous opacity or clump echo in front of the temporal spherical wall. Blood flow signals could be detected on the retinal folds with Doppler imaging.Conclusions:The CDFI manifestations of FEVR patients at different stages have different characteristics. The possibility of FEVR should be considered when the temporal or infratemporal retinal folds of both eyes are present, as well as the retinal folds of one eye, the contralateral vitreous body opacity, or the anterior temporal peribulbar cluster echoes are present.

Objective:To observe the ultrasonographic features of idiopathic uveal effusion syndrome (IUES).Methods:A retrospective controlled study. From January 2012 to December 2023, 13 patients with IUES (26 eyes) diagnosed by ophthalmology examination in Department of Ophthalmonogy of Beijing Tongren Hospital (IUES group) and 22 healthy people with 30 eyes (control group) were included in the study. Both eyes of all participants were examined by color Doppler ultrasound (CDU) and ultrasonic biomicroscopy (UBM). The thickness of the ocular wall at 300 μm on the temporal side of the optic disc was measured by CDU. UBM was used to measure the thickness of the nasal and temporal scleral processes. Corneal thickness (CT), anterior chamber depth (AD), lens thickness (LT) and axial length (AL) were measured by A-mode ultrasound. There were no significant differences in age ( t=0.842), sex component ratio ( χ2=0.540), eye difference ( χ2=0.108) and AL ( t=0.831) between IUES group and control group ( P>0.05). The CDU and UBM imaging features and biometrics of IUES affected eyes were observed. Independent sample t test was used for comparison between groups. Results:CDU examination results showed that in 26 eyes of IUES group, choroidal detachment occurred in 20 eyes (76.9%, 20/26), which showed arc-shaped band echo connected with peripheral and equatorial eye wall echo, with uniform low echo area below, and blood flow signal could be seen on the band echo. The echo thickened and decreased in 4 eyes (15.3%, 4/26). Nine eyes (33.3%, 9/26) were accompanied by retinal detachment, which showed that the posterior pole vitreous echo was connected to the optic disc echo, and the blood flow signal was seen on the ribbon echo. UBM results showed ciliary detachment in 22 eyes (84.7%, 22/26), showing a spongy thickening of the ciliary body with interlamellar echo separation and an echoless area between the sclera. Ciliary body echo thickened and decreased in 2 eyes (7.7%, 2/26). Shallow space between ciliary body and sclera was observed in 2 eyes (7.7%, 2/26). Compared with the control group, CT ( Z=2.054), LT ( Z=1.867), scleral thickness ( Z=2.536) and ocular wall thickness ( Z=2.094) were thickened in IUES group, and AD ( Z=1.888) were decreased, with statistical significance ( P<0.05). Conclusions:The CDU of IUES is characterized by a thickened echo of the ocular wall and a uniform low echo area under the detached choroid. UBM is characterized by a spongy thickening of the ciliary body echo with interlaminar echo separation.

Objective:To observe the color Doppler flow imaging (CDFI) features of vitreoretinal lymphoma (VRL).Methods:Retrospective case series. From January 2022 to December 2024, 71 eyes of 42 patients diagnosed with VRL at the Eye Center of Beijing Tongren Hospital were enrolled. Among them, 17 were male and 25 female; 29 had bilateral and 13 unilateral involvement. Age ranged 17-78 years (median 59 years). Eleven cases had histopathologic confirmation and 31 were clinically diagnosed. All patients underwent CDFI and optical coherence tomography (OCT). CDFI findings were analyzed, noting the presence or absence of vitreous opacities (centrifugal distribution), posterior vitreous detachment (PVD), retinal detachment, and retinal elevated lesions. With Doppler overlay, blood flow within retinal lesions was assessed. The χ 2 test was used to compare the detection rates of retinal lesions by CDFI and OCT, while Cohen’s Kappa assessed agreement in identifying the depth of lymphoma cell infiltration. Results:Among 71 eyes, vitreous opacity occurred in 66 eyes (93.0%, 66/71), of which 40 eyes (60.6%, 40/66) showed centrifugal opacity. 58 eyes (81.7%, 58/71) had posterior vitreous detachment. Retinal detachment occurred in 7 eyes (9.9%, 7/71). Retinal occupying lesions occurred in 23 eyes (32.4%, 23/61), of which 15 eyes (65.2%, 15/23) showed blood flow signals on the surface of the lesions but no blood flow signals inside the lesions by CDFI, and OCT showed that tumor cells gathered under the retinal pigment epithelium. CDFI showed blood flow signals inside the lesions in 8 eyes (34.8%, 8/23), and OCT showed that tumor cells gathered between retinal neuroepithelial layers. The lesion detection rate of OCT (69.6%, 16/23) was significantly lower than that of CDFI (100.0%, 23/23) ( χ 2= 6.066, P=0.014). OCT and CDFI showed perfect agreement in determining the depth of tumor cell infiltration (Kappa=1.0). Conclusions:The ultrasonographic manifestations of VRL include vitreous opacity, PVD, and some retinal occupying lesions. Vitreous opacity often presents a characteristic centrifugal distribution. By observing whether there is blood flow signal in retinopathy using Doppler, the level of lymphoma cell infiltration can be suggested.

ObjectiveTo investigate the influence of platelet-albumin-bilirubin （PALBI） score on the textbook outcome （TO） of patients with hepatocellular carcinoma （HCC） after hepatectomy， as well as the association of different PALBI scores before surgery with the achievement of TO after hepatectomy in HCC patients. MethodsA retrospective analysis was performed for the data of HCC patients who underwent hepatectomy in West China Hospital of Sichuan University and Ziyang Central Hospital from January 2013 to January 2022. TO was defined as no serious complication within 30 days after surgery， no death within 90 days， no rehospitalization within 30 days after discharge， no blood transfusion in the perioperative period， RO resection， and no prolongation of hospital stay. The chi-square test was used for comparison of categorical data between two groups. The univariate and multivariate Logistic regression analyses were used to investigate the influencing factors for the achievement of TO after hepatectomy in HCC patients. The Kaplan-Meier method was used to plot the survival curves of HCC patients， and the Log-rank test was used for comparison. ResultsA total of 3 599 patients were included in this study， among whom 2 369 （65.8%） achieved TO. The multivariate Logistic regression analysis showed that PALBI grade （PALBI grade 2： odds ratio ［OR］=1.562， 95% confidence interval ［CI］： 1.308‍ ‍—‍ ‍1.864， P<0.001； PALBI grade 3： OR=2.216， 95%CI： 1.463‍ ‍—‍ ‍3.359， P<0.001） was an independent risk factor for achievement of TO after surgery in HCC patients. The proportion of patients achieving TO decreased with the increase in PALBI grade. Among the patients with PALBI grade 1， 2 or 3， the patients achieving TO accounted for 70.2%， 54.2%， and 38.4%， respectively （χ²=106.295， P<0.001）. The incidence rate of serious complications within 30 days， the mortality rate of patients within 90 days after hepatectomy， readmission rate within 30 days after discharge， perioperative blood transfusion rate， and the rate of prolonged hospital stay all increased with the increase in PALBI grade （all P<0.05）. For the patients achieving TO， the 1-， 3-， and 5-year relapse-free survival rates were 79.5%， 60.6%， and 51.5%， respectively， and the overall survival rates were 92.1%， 80.0%， and 71.1%， respectively； for those who did not achieve TO， the 1-， 3-， and 5-year relapse-free survival rates were 68.5%， 52.7%， and 46.2%， respectively， and the overall survival rates were 83.3%， 66.0%， and 57.1%， respectively. The patients who achieved TO had significantly better relapse-free survival rate and overall survival rate than those who did not achieve TO （χ²=18.936 and 79.371， both P<0.001）. ConclusionPreoperative PALBI grade can affect the achievement of TO after hepatectomy in HCC patients， and it is more difficult for patients with a higher PALBI grade to achieve TO. Preoperative PALBI score can be used to early identify the patients with a high risk of postoperative complications， provide early intervention， and enhance perioperative management， thereby improving the perioperative safety and long-term prognosis of HCC patients after hepatectomy.

Background Air pollution remains a critical public health issue, with persistent exposure to air pollutants continuing to pose significant health risks. Currently, research investigating the association between air pollution and myocardial infarction mortality in Shenzhen remains inadequate. Objective To quantitatively assess the association between air pollutants and myocardial infarction mortality in residents. Methods Based on the mortality surveillance system of Shenzhen Center for Disease Control and Prevention, we conducted a time-stratified case-crossover study of 10089 permanent residents who died from myocardial infarction in Shenzhen between 2013 and 2022. Using residential address information, we obtained individual-level exposure data for air pollutants from the China High Air Pollutants dataset and meteorological factors from the China Meteorological Administration Land Data Assimilation System. A time-stratified case-crossover study design was employed to construct a conditional logistic regression model to assess the association between short-term exposure to air pollutants and myocardial infarction mortality. The exposure-response relationship was visualized, and a comprehensive health risk assessment was performed. Results This study included a total of 10 089 cases of myocardial infarction deaths in Shenzhen. The median [interquartile range (IQR)] concentrations of fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), and ozone (O₃) in Shenzhen from 2013 to 2022 were 24.59 (20.19) μg·m⁻³, 42.85 (28.42) μg·m⁻³, 8.53 (3.39) μg·m⁻³, 29.47 (13.56) μg·m⁻³, 0.77 (0.27) mg·m⁻³, and 86.53 (51.39) μg·m⁻³, respectively. The moving average concentrations of PM_2.5 and PM₁₀ over the current day and the previous 2 days (lag02) showed the highest risk of myocardial infarction mortality, with an odds ratio (OR) and 95% confidence interval (95%CI) of 1.004 (1.001, 1.007) and 1.004 (1.002, 1.006), respectively. At lag05, SO₂ demonstrated the strongest association with the risk of myocardial infarction mortality, with an OR (95%CI) of 1.042 (1.019, 1.065). The exposure-response relationships of PM_2.5, PM₁₀, and SO₂ with myocardial infarction mortality were approximately linear, whereas NO₂ exhibited a nonlinear relationship. At lag05, the highest risk of myocardial infarction mortality associated with NO₂ exposure was observed when the NO₂ concentration was ≤21.92 μg·m⁻³, with an OR (95% CI) of 1.024 (1.003, 1.046). The health risk assessment indicated that, using the WHO Air Quality Guidelines as the reference, the local PM_2.5 and NO₂ exposure led to an excess mortality of 398 and 298 cases, respectively. The sensitivity analysis revealed that after adjusting for O₃ and restricting the study period to 2013—2019, the effect estimates for PM_2.5, PM₁₀, NO₂, and SO₂ on myocardial infarction mortality slightly increased. Conclusion Short-term exposure to air pollutants, including PM_2.5, PM₁₀, NO₂, and SO₂, could increase the risk of myocardial infarction mortality. This study provides important scientific evidence for environmental health risk assessment and environmental management in Shenzhen.