Coronavirus disease 2019 (COVID-19) is a multi-system disease that can lead to various severe complications. Acute limb ischemia (ALI) has been increasingly recognized as a COVID-19-associated complication that often predicts a poor prognosis. However, the pathophysiology and molecular mechanisms underlying COVID-19-associated ALI remain poorly understood. Hypercoagulability and thrombosis are considered important mechanisms, but we also emphasize the roles of vasospasm, hypoxia, and acidosis in the pathogenesis of the disease. The angiotensin-converting enzyme 2 (ACE2) pathway, inflammation, and platelet activation may be important molecular mechanisms underlying these pathological changes induced by COVID-19. Furthermore, we discuss the hypotheses of risk factors for COVID-19-associated ALI from genetic, age, and gender perspectives based on our analysis of molecular mechanisms. Additionally, we summarize therapeutic approaches such as use of the interleukin-6 (IL-6) blocker tocilizumab, calcium channel blockers, and angiotensin-converting enzyme inhibitors, providing insights for the future treatment of coronavirus-associated limb ischemic diseases.
Humans ; COVID-19/physiopathology* ; Ischemia/etiology* ; SARS-CoV-2 ; Extremities/blood supply* ; Risk Factors ; Interleukin-6/antagonists & inhibitors* ; Acute Disease ; Angiotensin-Converting Enzyme 2

The precise and rapid monitoring of multiple organ dysfunction is crucial in drug discovery. Traditional methods, such as pathological analysis, are often time-consuming and inefficient. Here, we developed a multiplexed near-infrared window two (NIR-II) fluorescent bioimaging method that allows for real-time, rapid, and quantitative assessment of multiple organ dysfunctions. Given that existing probes did not fully meet requirements, we synthesized a range of NIR-II hemicyanine dyes (HDs) with varying absorption and emission wavelengths. By modifying these dyes, we achieved high spatial and temporal resolution imaging of the liver, kidneys, stomach, and intestines. This method was further applied to investigate disorders induced by cisplatin, a drug known to cause gastric emptying issues along with liver and kidney injuries. By monitoring the metabolic rate of the dyes in these organs, we accurately quantified multi-organ dysfunction, which was also confirmed by gold-standard pathological analysis. Additionally, we evaluated the effects of five aristolochic acids (AAs) on multiple organ dysfunction. For the first time, we identified that AA-I and AA-II could cause gastric emptying disorders, which was further validated through transcriptomics analysis. Our study introduces a novel approach for the simultaneous monitoring of multi-organ dysfunction, which may significantly enhance the evaluation of drug side effects.

Virus-related lymphoma exhibits a dual nature as both a hematologic malignancy and a viral infectious disease， making it more resistant to treatment and associated with poorer prognosis. This paper analyzes the understanding and therapeutic advantages of traditional Chinese medicine （TCM） in virus-related lymphoma. It proposes a TCM-based approach centered around syndrome differentiation， using standardized measurements of the overall TCM condition， multi-omics research of hematologic tumors， and artificial intelligence technologies to identify the "pre-condition" of virus-related lymphoma. A risk warning model will be established to early identify high-risk populations with viral infections that may develop into malignant lymphoma， thereby establishing a risk warning system for virus-related lymphoma. At the same time， a TCM health management approach will be applied to manage and regulate virus-related lymphoma， interrupting its progression and forming a human-centered， comprehensive， continuous health service model. Based on this， a standardized， integrated clinical prevention and treatment decision-making model for virus-related lymphoma， recognized by both Chinese and western medicine， will be established to provide TCM solutions for primary prevention of major malignant tumors.

Objective: To investigate the distribution of traditional Chinese medicine (TCM) syndromes and syndrome elements in lymphoma, as well as the correlation between TCM syndromes and Western clinical indicators, in order to analyze associations between TCM syndromes and these indicators. Methods: From January 2023 to May 2024, 216 patients with lymphoma who met the inclusion criteria in the Department of Hematology, Third People′s Hospital Affiliated to Fujian University of Traditional Chinese Medicine were enrolled. Four diagnostic methods were applied to perform TCM syndrome differentiation and extract syndrome elements. The correlations between various syndromes and blood test indicators of lactate dehydrogenase (LDH), β2-microglobulin (β2-MG), immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), white blood cell (WBC), hemoglobin (Hb), platelet count (PLT), neutrophil (NEUT), immunohistochemical markers of B-cell lymphoma-6 (BCL6), B-cell lymphoma-2 (BCL2), proto-oncogene MYC, and Ki67 protein expression, Ann Arbor staging, international prognostic index (IPI) score, bone marrow infiltration, concurrent infections during chemotherapy, and post-chemotherapy bone marrow suppression rate were analyzed. Results: Five TCM syndromes, ranked by frequency, were syndromes of yin deficiency with phlegm accumulation(41.67%), qi depression with phlegm obstruction(30.56%), cold-phlegm congelation and stagnation(12.96%), phlegm-blood stasis toxin(12.04%), and lingering pathogen due to deficient vital qi(2.77%). Yin deficiency(50.93%) and phlegm(45.37%) were the more prevalent syndrome elements. The TCM syndromes were correlated with β2-MG, PLT, MYC, BCL2/MYC, Ki67 protein expression, and bone marrow infiltration (P<0.05). No statistically significant differences were observed in Ann Arbor staging or IPI score across the syndromes. Compared to the syndrome of cold-phlegm congelation and stagnation, the syndrome of qi depression with phlegm obstruction exhibited higher levels of NEUT, MYC, BCL2/MYC, and Ki67 protein expression, as well as a higher rate of post-chemotherapy bone marrow suppression (P<0.05); the syndrome of phlegm-blood stasis toxin showed higher MYC and BCL2/MYC protein expression and a higher rate of post-chemotherapy bone marrow suppression rate (P<0.05); the syndrome of yin deficiency with phlegm accumulation demonstrated higher MYC and BCL2/MYC protein expression and bone marrow infiltration rates, whereas PLT level was lower (P<0.05); the syndrome of lingering pathogen due to deficient vital qi had higher MYC, BCL2/MYC, and Ki67 protein expression levels, as well as a higher rate of post-chemotherapy bone marrow suppression rate (P<0.05). Compared to the syndrome of qi depression with phlegm obstruction, the syndrome of phlegm-blood stasis toxin exhibited lower Ki67 protein expression (P<0.05); the syndrome of yin deficiency with phlegm accumulation had higher β2-MG level, bone marrow infiltration rate, and rate of concurrent infections during chemotherapy, whereas PLT and NEUT levels and the rate of post-chemotherapy bone marrow suppression rate were lower (P<0.05). Compared to the syndrome of phlegm-blood stasis toxin, the syndrome of yin deficiency with phlegm accumulation had higher β2-MG level, whereas NEUT and the rate of post-chemotherapy bone marrow suppression were lower(P<0.05); the syndrome of lingering pathogen due to deficient vital qi exhibited a higher Ki67 protein expression (P<0.05). Compared to the syndrome of yin deficiency with phlegm accumulation, the syndrome of lingering pathogen due to deficient vital qi also showed a higher Ki67 protein expression(P<0.05). Conclusion The syndrome of yin deficiency with phlegm accumulation is relatively common in lymphoma. There is a correlation between TCM syndromes and Western medicine clinical indicators. The presence of heat signs in the syndromes may indicate active disease and poor prognosis, while the presence of strong pathogenic factors and weak vital qi in the syndromes may indicate a severer chemotherapy-related bone marrow suppression.

Objective:To explore the diagnostic value of fractional flow reserve (FFR) based on optical coherence tomography (OCT) for coronary functional ischemia, and to investigate the feasibility of synchronously obtaining Doppler blood flow velocity information with the help of OCT technology.Methods:This study was a single-center, prospective, self-controlled clinical study on coronary heart disease patients who underwent OCT and FFR assessment at Department of Cardiology, the Second Hospital of Jilin University from January 2024 to February 2025. Linear regression analysis was used to evaluate the correlation and consistency between OCT-FFR and FFR. With FFR≤0.80 as the gold standard for judging whether the target vessel was ischemic, the diagnostic performance of OCT-FFR was evaluated, and the diagnostic value of OCT-FFR for significant coronary artery ischemia was assessed using subject operating characteristic curves. Blood flow OCT data were analyzed by Doppler processing algorithm to obtain information on coronary blood flow velocity.Results:A total of 31 vessels from 28 patients were analyzed, the correlation coefficient r between OCT-FFR and FFR of the 31 vessels was 0.84 ( P<0.001). With FFR as the gold standard to determine whether a coronary artery is ischemic, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for OCT-FFR was 93.55%, 75.00%, 100.00%, 1.00, 0.92. In clinical practice, Doppler OCT was used for the first time to obtain information on coronary blood flow velocity. Conclusion:OCT-FFR had an excellent correlation and consistency with FFR in judging whether there is coronary artery ischemia. The feasibility of the simultaneous acquisition of OCT-FFR and Doppler flow velocity information in coronary stenosis was preliminarily verified.

Objective To explore the characteristics of upper airway obstruction on multi spiral computed tomography(MSCT)in patients with obstructive sleep apnea hypopnea syndrome(OSAHS)and their correlation with the disease,as well as to identify key characteristic indicators.Methods Forty-three patients with OSAHS(OSAHS group)and 45 normal controls(control group)were selected.MSCT of the upper airway was performed to analyze the differences in various observation indicators between the two groups,including diameters at levels of upper airway obstruction,soft palate thickness,mandibular plane to hyoid distance(MP-H),oropharyngeal length,air-pharyngeal ratio,and fat infiltration in the tongue base.A multivariate logistic regression model was con-structed to identify the main risk factors,and the receiver operating characteristic(ROC)curve was used to assess the diagnostic per-formance of the model.Results The OSAHS group exhibited smaller diameters at levels of upper airway obstruction and air-pharyn-geal ratio compared to the control group[area:(0.75±0.38)cm2 vs(1.36±0.58)cm2,t=5.855,P＜0.001].Additionally,body mass index(BMI),degree of fat infiltration in the tongue base,soft palate thickness,and MP-H were significantly greater in the OSAHS group than those in the control group(soft palate thickness:t=-6.881,P＜0.001).Multivariate logistic regression analysis revealed that fat infiltration in the tongue base,soft palate thickness,MP-H,and the area of upper airway obstruction were the main risk factors for OSAHS.The area under the curve(AUC)was 0.940[95％confidence interval(CI)0.868-0.979,P＜0.001],indica-ting good diagnostic performance.Conclusion MSCT can effectively evaluate the upper airway obstruction characteristics in patients with OSAHS,with fat infiltration in the tongue base,soft palate thickness,MP-H,and the area of upper airway obstruction as the primary indicators for OSAHS,providing a reference for clinical practice.

Objective To explore the characteristics of upper airway obstruction on multi spiral computed tomography(MSCT)in patients with obstructive sleep apnea hypopnea syndrome(OSAHS)and their correlation with the disease,as well as to identify key characteristic indicators.Methods Forty-three patients with OSAHS(OSAHS group)and 45 normal controls(control group)were selected.MSCT of the upper airway was performed to analyze the differences in various observation indicators between the two groups,including diameters at levels of upper airway obstruction,soft palate thickness,mandibular plane to hyoid distance(MP-H),oropharyngeal length,air-pharyngeal ratio,and fat infiltration in the tongue base.A multivariate logistic regression model was con-structed to identify the main risk factors,and the receiver operating characteristic(ROC)curve was used to assess the diagnostic per-formance of the model.Results The OSAHS group exhibited smaller diameters at levels of upper airway obstruction and air-pharyn-geal ratio compared to the control group[area:(0.75±0.38)cm2 vs(1.36±0.58)cm2,t=5.855,P＜0.001].Additionally,body mass index(BMI),degree of fat infiltration in the tongue base,soft palate thickness,and MP-H were significantly greater in the OSAHS group than those in the control group(soft palate thickness:t=-6.881,P＜0.001).Multivariate logistic regression analysis revealed that fat infiltration in the tongue base,soft palate thickness,MP-H,and the area of upper airway obstruction were the main risk factors for OSAHS.The area under the curve(AUC)was 0.940[95％confidence interval(CI)0.868-0.979,P＜0.001],indica-ting good diagnostic performance.Conclusion MSCT can effectively evaluate the upper airway obstruction characteristics in patients with OSAHS,with fat infiltration in the tongue base,soft palate thickness,MP-H,and the area of upper airway obstruction as the primary indicators for OSAHS,providing a reference for clinical practice.

Objective:To explore the diagnostic value of fractional flow reserve (FFR) based on optical coherence tomography (OCT) for coronary functional ischemia, and to investigate the feasibility of synchronously obtaining Doppler blood flow velocity information with the help of OCT technology.Methods:This study was a single-center, prospective, self-controlled clinical study on coronary heart disease patients who underwent OCT and FFR assessment at Department of Cardiology, the Second Hospital of Jilin University from January 2024 to February 2025. Linear regression analysis was used to evaluate the correlation and consistency between OCT-FFR and FFR. With FFR≤0.80 as the gold standard for judging whether the target vessel was ischemic, the diagnostic performance of OCT-FFR was evaluated, and the diagnostic value of OCT-FFR for significant coronary artery ischemia was assessed using subject operating characteristic curves. Blood flow OCT data were analyzed by Doppler processing algorithm to obtain information on coronary blood flow velocity.Results:A total of 31 vessels from 28 patients were analyzed, the correlation coefficient r between OCT-FFR and FFR of the 31 vessels was 0.84 ( P<0.001). With FFR as the gold standard to determine whether a coronary artery is ischemic, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for OCT-FFR was 93.55%, 75.00%, 100.00%, 1.00, 0.92. In clinical practice, Doppler OCT was used for the first time to obtain information on coronary blood flow velocity. Conclusion:OCT-FFR had an excellent correlation and consistency with FFR in judging whether there is coronary artery ischemia. The feasibility of the simultaneous acquisition of OCT-FFR and Doppler flow velocity information in coronary stenosis was preliminarily verified.

Objective:To investigate the efficacy and safety of oral semaglutide in Chinese patients with type 2 diabetes mellitus(T2DM) inadequately controlled by diet and exercise only.Methods:In the randomized, double-blind, multicenter, multinational PIONEER-11 trial, Chinese patients were prospectively randomly assigned to receive oral semaglutide 3, 7, or 14 mg, or placebo. The primary endpoint was the change from baseline in glycated hemoglobin(HbA 1C) at week 26. This is a pre-defined subset analysis to assess the efficacy and safety in Chinese patients. Results:Totally 390 Chinese T2DM patients were enrolled(mean age 51 years), with a T2DM duration of 1.8 years, HbA 1C of 7.9%, and BMI of 26.5 kg/m 2 at baseline. Overall, changes at week 26 from baseline in HbA 1C were -1.1%, -1.6%, -1.6%, and 0.0%, and in bodyweight were -0.7, -1.9, -2.6, and -0.7 kg in oral semaglutide(3, 7, or 14 mg) and placebo groups, respectively. Compared to the placebo group, estimated treatment differences(ETDs) in HbA 1C for the 3, 7, and 14 mg groups were -1.2%(95% CI -1.4, -0.9), -1.7%(95% CI -1.9, -1.4), and -1.6%(95% CI -1.9, -1.4)(all P<0.001), respectively, and in weight loss for the 7 mg and 14 mg groups were -1.2 kg(95% CI -2.1, -0.4; P=0.006) and -1.9 kg(95% CI -2.8, -1.0; P<0.001), respectively. The most frequent gastrointestinal adverse events were diarrhea(oral semaglutide: 3.1%-12.5% vs placebo: 2.0%) and nausea(3.1%-6.3% vs 2.0%), mostly mild in severity and transient. Conclusion:In Chinese patients with T2DM who had insufficient glycemic control with diet and exercise only, oral semaglutide showed better glycemic control at doses of 3, 7, and 14 mg and more weight loss at doses of 7 and 14 mg compared to placebo, with a safety profile consistent with that observed in the global trial population.

Objective:To prepare the chitin/hyaluronic acid/collagen hydrogel loaded with mouse adipose-derived stem cells and to explore its effects on wound healing of full-thickness skin defects in rats.Methods:The research was an experimental research. Chitin nanofibers were prepared by acid hydrolysis and alkaline extraction method, and then mixed with hyaluronic acid and collagen to prepare chitin/hyaluronic acid/collagen hydrogels (hereinafter referred to as hydrogels). Besides, the hydrogels loaded with mouse adipose-derived stem cells were prepared. Thirty male 12-week-old guinea pigs were divided into negative control group, positive control group, and hydrogel group according to the random number table, with 10 guinea pigs in each group. Ethanol, 4-aminobenzoic acid ethyl ester, or the aforementioned prepared hydrogels without cells were topically applied on both sides of back of guinea pigs respectively for induced contact and stimulated contact, and skin edema and erythema formation were observed at 24 and 48 h after stimulated contact. Adipose-derived stem cells from mice were divided into normal control group cultured routinely and hydrogel group cultured with the aforementioned prepared hydrogels without cells. After 3 d of culture, protein expressions of platelet-derived growth factor-D (PDGF-D), insulin-like growth factor-Ⅰ (IGF-Ⅰ), and transforming growth factor β 1 (TGF-β 1) were detected by Western blotting ( n=3). Eight male 8-week-old Sprague-Dawley rats were taken and a circular full-thickness skin defect wound was created on each side of the back. The wounds were divided into blank control group without any treatment and hydrogel group with the aforementioned prepared hydrogels loaded with adipose-derived stem cells applied. Wound healing was observed at 0 (immediately), 2, 4, 8, and 10 d after injury, and the wound healing rate was calculated at 2, 4, 8, and 10 d after injury. Wound tissue samples at 10 d after injury were collected, the new tissue formation was observed by hematoxylin-eosin staining; the concentrations of interleukin-1α (IL-1α), IL-6, IL-4, and IL-10 were detected by enzyme-linked immunosorbent assay method; the expressions of CD16 and CD206 positive cells were observed by immunohistochemical staining and the percentages of positive cells were calculated. The sample numbers in animal experiment were all 8. Results:At 24 h after stimulated contact, no skin edema was observed in the three groups of guinea pigs, and only mild skin erythema was observed in 7 guinea pigs in positive control group. At 48 h after stimulated contact, skin erythema was observed in 8 guinea pigs and skin edema was observed in 4 guinea pigs in positive control group, while no obvious skin erythema or edema was observed in guinea pigs in the other two groups. After 3 d of culture, the protein expression levels of PDGF-D, IGF-I, and TGF-β 1 in adipose-derived stem cells in hydrogel group were significantly higher than those in normal control group (with t values of 12.91, 11.83, and 7.92, respectively, P<0.05). From 0 to 10 d after injury, the wound areas in both groups gradually decreased, and the wounds in hydrogel group were almost completely healed at 10 d after injury. At 4, 8, and 10 d after injury, the wound healing rates in hydrogel group were (38±4)%, (54±5)%, and (69±6)%, respectively, which were significantly higher than (21±6)%, (29±7)%, and (31±7)% in blank control group (with t values of 3.82, 3.97, and 4.05, respectively, Pvalues all <0.05). At 10 d after injury, compared with those in blank control group, the epidermis in wound in hydrogel group was more intact, and there were increases in hair follicles, blood vessels, and other skin appendages. At 10 d after injury, the concentrations of IL-1α and IL-6 in wound tissue in hydrogel group were significantly lower than those in blank control group (with tvalues of 8.21 and 7.99, respectively, P<0.05), while the concentrations of IL-4 and IL-10 were significantly higher than those in blank control group (with tvalues of 6.57 and 9.03, respectively, P<0.05). The percentage of CD16 positive cells in wound tissue in hydrogel group was significantly lower than that in blank control group ( t=8.02, P<0.05), while the percentage of CD206 positive cells was significantly higher than that in blank control group ( t=7.21, P<0.05). Conclusions:The hydrogel loaded with mouse adipose-derived stem cells is non-allergenic, can promote the secretion of growth factors in adipose-derived stem cells, promote the polarization of macrophages to M2 phenotype in wound tissue in rats with full-thickness skin defects, and alleviate inflammatory reaction, thereby promoting wound healing.