AIM: To analyze the pathological features, immunophenotype, and imaging findings of conjunctival lymphangiectasia(CL), and to explore the etiological mechanisms and provide a theoretical basis for clinical diagnosis and treatment. METHODS:This single-center descriptive cross-sectional study enrolled postoperative specimens from patients with CL who underwent surgical treatment in the hospital between Feb. 2023 and Sept. 2025. Routine hematoxylin and eosin(HE)staining and immunohistochemical staining(D2-40, CD31, CD34, CK)were performed. Anterior segment optical coherence tomography(AS-OCT)was used to observe the lesion morphology. The pathological results were comprehensively analyzed combined with clinical data. RESULTS: A total of postoperative specimens from 32 eyes of 32 patients with CL were enrolled, including 23 females(72%)and 9 males(28%), with a mean age of 53.03±12.47 y. All patients presented with single or multiple transparent cystic elevations beneath the bulbar conjunctiva. The postoperative pathological manifestations were characterized by dilation of conjunctival lymphatic vessels lined with a single layer of flattened endothelial cells, accompanied by edema and inflammatory infiltration in the surrounding stroma. All cases were positive for D2-40, confirming a lymphatic origin; some cases also expressed CD31 and CD34. AS-OCT revealed the lesions as unilocular or multilocular cystic spaces with low reflectivity. After complete surgical resection, the mean follow-up period was 16.2 mo with no recurrence.CONCLUSION:CL is a benign ocular surface lesion characterized by lymphatic vessel dilation. The endothelium co-expresses lymphatic and some vascular markers, suggesting that CL may belong to the spectrum of vascular malformations. AS-OCT has adjunctive diagnostic value, and surgical resection has definitive therapeutic efficacy.

Under the background of forensic medicine becoming a first-level discipline,the opportuni-ties and challenges of discipline development coexist.Starting from the actual situation and characteris-tics of local medical colleges and universities,this paper discusses the problems and solutions for the development of forensic medicine discipline from the perspective of building a regional high-level medical university.Combined with the experiences of carrying out forensic medicine education in our college,this paper supplies our thoughts and practices on improving the discipline system,enhancing the ability to serve society,perfecting the talent cultivation model and promoting forensic culture,to provide reference and inspiration for the development of forensic medicine in other universities,jointly promote the advancement of forensic medicine in China to a new stage,and contribute the wisdom and strength of forensic medical experts to the construction of a law-based China,a safe China and a healthy China.

Objective To explore the brain damage of SD rats under different time points of hypobaric hypoxia exposure.Methods A rat high-altitube cerebral edema(HACE)model was constructed by simulating an altitude of 6 000 m in a hypobaric hypoxia animal experimental chamber.Thirty-six SD male rats were randomly divided into the control group and the hypobaric hypoxia exposure 3,7 and 14 d groups,with 9 rats in each group.Except for the control group,the rats in each group were continuously exposed to hypobaric hypoxia for 3,7,and 14 d.At the end of the modeling period,serum was collected by blood sampling via the abdominal aorta,and brain tissue samples were taken.The wet-to-dry ratio(W/D)of brain tissue was calculated,and the levels of relevant oxidative enzymes in serum and brain tissue were measured.The expression levels of hypoxia-inducible factor-1α(HIF-1α)and aquaporin 4(AQP4)mRNAs in brain tissue were detected by real-time fluorescence quantitative polymerase chain reaction.Results The W/D of brain tissues in the control group and the group exposed to hypobaric hypoxia for 3,7 and 14 d were 4.46±0.12,4.98±0.16,5.07±0.18 and 4.95±0.07;the superoxide dismutase contents were(111.86±2.45),(90.73±1.48),(79.64±2.56)and(55.33±1.45)U·g-1;the glutathione contents were(126.91±5.18),(125.26±1.53),(56.20±2.17)and(122.73±1.78)μg·mL-1;the malondialdehyde contents were(230.94±2.00),(362.65±3.28),(407.34±3.47)and(237.50±1.59)nmol·g-1;the relative expression levels of HIF-1 α mRNA were 1.00±0,2.99±0.49,4.72±0.49 and 1.91±0.28;the relative expression levels of AQP4 mRNA were 1.00±0,2.62±0.34,8.38±0.84 and 5.27±0.42,respectively.Statistically significant differences were found between the above indexes in the 3,7 and 14 d of hypobaric hypoxia exposure group compared with the control group(P＜0.05,P＜0.01).Conclusion Different time of hypobaric hypoxia exposure can up-regulate the expression of AQPs proteins in HACE rats and cause the disruption of the blood-brain barrier,and the HACE model constructed in the hypobaric hypoxia chamber with 6 000 m intervention for 7 d was more stable.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

OBJECTIVE: To explore the implementation effect of hour-1 bundle for sepsis patients based on crisis resource management (CRM) system. METHODS: A historical control study was conducted. The hour-1 bundle for sepsis based on CRM was used to train 24 nurses in the emergency department from October 2022 to March 2023. Clinical data of sepsis patients admitted to the emergency department of the First People's Hospital of Zunyi from April 2022 to September 2023 were collected. The patients were divided into three groups based on different stages of CRM system construction: control group (before construction, from April to September in 2022), improvement group (during construction, from October 2022 to March 2023) and observation group (after construction, from April to September in 2023). The baseline data, implementation rate of hour-1 bundle [including blood culture, antibiotic usage, blood lactic acid (Lac) detection, fluid resuscitation, hypertensors usage], identification and diagnosis time, and prognosis parameters [including correction rate of hypoxemia, intensive care unit (ICU) occupancy rate, and 28-day survival rate]. Sepsis cognition survey and non-technical skill (NTS) evaluation of nurses in emergency department were conducted before and after training. RESULTS: Finally 43 cases were enrolled in the control group, improvement group and observation group, respectively. There was no statistically significant difference in baseline data including the gender, age, primary site, heart rate, systolic blood pressure, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, mechanical ventilation ratio among the three groups with comparability. With the gradual improvement of the CRM system, the implementation rate of 1-hour bundle was gradually increased, and the implementation rate in the control group, improvement group and observation group were 65.12% (28/43), 74.42% (32/43) and 88.37% (38/43), respectively, with statistically significant difference (P < 0.05). It was mainly reflected in the completion rate of blood culture, antibiotic usage rate, Lac detection rate and hypertensors usage rate within 1 hour, which were significantly higher in the observation group than those in the control group [completion rate of blood culture: 90.70% (39/43) vs. 62.79% (27/43), antibiotic usage rate: 88.37% (38/43) vs. 60.47% (26/43), Lac detection rate: 93.02% (40/43) vs. 72.09% (31/43), hypertensors usage rate: 88.37% (38/43) vs. 60.47% (26/43), all P < 0.05]. The fluid resuscitation rates within 1 hour in the three groups were all over 90%, with no statistically significant difference among the three groups. The recognition and diagnosis time in the observation group was significantly shorter than that in the control group and the improvement group (hours: 0.41±0.15 vs. 0.61±0.21, 0.51±0.18, both P < 0.05), the correction rate of hypoxemia and 28-day survival rate were significantly higher than those in the control group [correction rate of hypoxemia: 95.35% (41/43) vs. 74.42% (32/43), 28-day survival rate: 83.72% (36/43) vs. 60.47% (26/43), both P < 0.05], and ICU occupancy rate was significantly lower than that in the control group [72.09% (31/43) vs. 93.02% (40/43), P < 0.05]. After training in the CRM system, the score of the sepsis awareness survey questionnaire for emergency department nurses was significantly increased as compared with before training (60.42±5.29 vs. 44.17±9.21, P < 0.01), and NTS also showed significant improvement. CONCLUSION CRM plays a significant role in promoting the implementation of sepsis hour-1 bundle, which can improve the implementation rate of hour-1 bundle and NTS of medical staff, effectively improve patients' hypoxemia, reduce patients' ICU occupancy rate and 28-day risk of death.
Humans ; Sepsis/therapy* ; Emergency Service, Hospital ; Patient Care Bundles ; Intensive Care Units ; Female ; Male ; Middle Aged

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Objective:To compare the efficacy of anrikefon and tegileridine for analgesia in patients with moderate-to-severe pain after abdominal surgery with general anesthesia.Methods:In this multicenter, randomized, double-blind, active-controlled clinical trial, 101 patients with moderate to severe pain (numeric pain rating scale [NRS] score ≥4 within 4 h after operation) after abdominal surgery with general anesthesia between February 24 and April 1, 2025, aged 18-70 yr, with a body mass index of 18-40 kg/m 2, were assigned to anrikefon group ( n=50) and tegileridine group ( n=51) in a 1∶1 ratio using stratified blocked randomization. Double-dummy design was employed to maintain blinding. Each group received an initial intravenous injection of anrikefon 1 μg/kg or tegileridine 1 mg, followed by connection to a patient-controlled intravenous analgesia (PCIA) pump (the PCIA solution contained normal saline in anrikefon group; the PCIA solution contained tegileridine 5 mg in tegileridine pump) within 10 min. If the patient′s NRS score ≥4 at 8 and 16 h after the initial injection, anrikefon 1 μg/kg was intravenously injected in anrikefon group, and tegileridine group received the equal volume of normal saline. The primary efficacy endpoint was the sum of pain intensity difference (SPID) over the first 24 h after the initial dose (SPID 0-24h). The secondary efficacy endpoints included the incidence and severity of vomiting and nausea, incidence of postoperative nausea and vomiting(PONV), the proportion of patients who received antiemetic treatment, and total consumption of antiemetics within 0-24 h after the initial dose, NRS score at rest ≤ 1 at 24 h after the initial dose, and NRS score at rest ≤ 3 over the first 24 h after the initial dose. Safety indicators included adverse events, vital signs, physical examination findings, 12-lead ECG and laboratory test indicators, and adverse events of special interest. Results:Compared with tegileridine group, no significant change was found in the SPID 0-24h ( P>0.05), and the incidence of vomiting, PONV, proportion of patients requiring antiemetic medication, and total consumption of antiemetics were significantly decreased within the first 24 h after the initial dose in tegileridine group ( P<0.05). One treatment-emergent adverse event of Common Terminology Criteria for Adverse Events grade 3 or higher occurred in tegileridine group, while no treatment-emergent adverse events of Common Terminology Criteria for Adverse Events grade 3 or higher were found in anrikefon group. Among the adverse events of special interest, one case of respiratory depression and one case of cough occurred in tegileridine group, while one case of cough occurred in anrikefon group, with no respiratory depression. Conclusions:Anrikefon and tegileridine provide comparable analgesic efficacy for moderate-to-severe pain after abdominal surgery with general anesthesia. However, anrikefon exhibits an advantage in reducing the risk of PONV, with a superior safety profile.

BACKGROUND:Traditional Chinese medicine has been proved to have a significant role in anti-osteoporosis,and the effectiveness and mechanism of Ligustri Lucidi Fructus and its the active ingredients against osteoporosis have gradually gained the attention of scholars.OBJECTIVE:To analyze and summarize the research progress of Ligustri Lucidi Fructus and its active ingredients against osteoporosis in vitro and in vivo.METHODS:We searched the relevant literature included in CNKI and PubMed databases using the search terms of"Osteoporosis,Bone marrow mesenchymal stem cells,Osteoblast,Osteoclast,Ligustri Lucidi Fructus,Signal path"in Chinese and English,respectively.According to the needs of the research,we established the corresponding criteria and screened the literature.A total of 82 papers were included in the final review.RESULTS AND CONCLUSION:(1)The active ingredients of Ligustri Lucidi Fructus that exert anti-osteoporotic effects in vitro and in vivo mainly involve the following:Salidroside activates the Wnt/β-catenin signaling pathway by inhibiting the expression of Sclerostin and Dickkopf-related protein 1.This activation process enhances the expression of phosphorylated low-density lipoprotein receptor-related protein 6 in ovariectomized rats and primary osteoblasts,while decreasing the expression of glycogen synthase kinase 3β.Further,it promotes the expression of β-catenin,runt-related transcription factor 2 and cellular myelocytomatosis oncogene in the nucleus,thereby promoting the bone formation capacity of osteoblasts.The advantage is that it acts directly on osteoblasts to promote bone formation,which provides a new strategy for the treatment of osteoporosis.(2)Olive bittersweet significantly increases bone mineral density and regulates bone metabolism by decreasing terminal interleukin-6 and alkaline phosphatase concentrations in Sprague-Dawley rats.In vitro experiments showed that olive bittersweet promotes the proliferation of osteoblasts and up-regulates the protein and mRNA expression of osteoprotegerin,while inhibiting the protein and mRNA expression of receptor activator of nuclear factor-κB ligand.This mechanism of action is closely related to the regulation of the balance of the osteoprotegerin/receptor activator of nuclear factor-κB ligand system,demonstrating the advantage of increasing bone mineral density and maintaining bone health by regulating factors related to bone metabolism,but there is no significant effect on Ca2+concentration,which may limit its use in some specific types of osteoporosis.(3)By decreasing the expression of phosphatidylinositol 3 kinase,reducing the phosphorylation of protein kinase B and the expression of osteoclast-specific marker protein c-Fos,pineconiferin effectively inhibits the activation of phosphatidylinositol 3 kinase/protein kinase B/c-Fos pathway in osteoclasts.This inhibition reduces the proliferation and maturation of osteoclasts,which can help to reduce bone resorption.The advantage of this inhibition is that it can directly target osteoclasts,which provides a new target for osteoporosis treatment.However,the specific regulatory mechanism of osteoclasts needs to be studied in depth,and its long-term effect and safety need to be further evaluated.(4)The active ingredients of Ligustri Lucidi Fructus have shown good therapeutic effects on osteoporosis,but their mechanism of action is complex,involving the interaction of multiple genes,proteins and signaling pathways.In the future,large-scale clinical trials need to be carried out to verify its effectiveness and safety,and the strategy of combining the active ingredients of Ligustri Lucidi Fructus with other drugs needs to be further explored in order to obtain better therapeutic effects.