Objective:To retrospectively analyze the changes in the proportion of refined lymphocyte subsets in peripheral blood of patients with Graves disease (GD), and their correlation with the clinical characteristics and efficacy of GD, and to explore the immunological pathogenesis of Graves disease for seeking new therapeutic targets.Methods:A total of 97 newly diagnosed GD patients (GD group), 27 patients after treatment (treatment group), and 31 healthy individuals (control group) who visited the Fifth Medical Center of the PLA General Hospital from 2018 to 2021 were included in this study. The data of refined lymphocyte subsets, thyroid function, blood routine and clinical treatment of the three groups were compared and analyzed. The t-test and rank sum test were used to compare the proportions of lymphocyte subsets among different groups, and Pearson correlation analysis was used to analyze the correlation between the proportions of lymphocyte subsets and thyroid function indicators.Results:The proportion of B cells in GD group was higher than that in the control group [16.2%(11.8%, 21.8%) vs 10.2%(8.1%,13.6%)], while the proportion of natural killer (NK) cells was lower [9.4%(4.9%, 13.6%) vs 14.6%(12.1%,18.8%)], and the differences were statistically significant ( P<0.05). Abnormal T cell differentiation: the proportions of functional cells, including activated T cells, memory T cells, clustering antigen(CD)4+memory T cells, Th1 cells, and Tc1 cells, were lower than that in the control group [3.2%(2.1%, 5.7%) vs 5.8%(3.0%, 9.3%), P<0.05; 36.7% (29.9%, 48.1%) vs 48.0%(39.2%,57.7%), P<0.05; 23.1%(17.4%, 30.1%) vs 28.9%(23.3%,34.6%), P<0.05; 16.4% (11.8%, 23.6%) vs 24.3%(16.9%,28.5%), P<0.05; 28.5% (14.7%, 39.2%) vs 46.3%(21.6%,69.2%), P<0.05]. The proportion of activated T cells in the treatment group was higher than that in the GD group [6.5% (4.6%, 13.6%) vs 3.2% (2.1%, 5.7%), P<0.05]. The total triiodothyronine results showed positive correlations with B cells ( r=0.356, P<0.01) and negative correlations with NK cells ( r=?0.416, P<0.01), while the total thyroxine values showed negative correlations with NK cells and activated T cells ( r=?0.318,?0.335; P<0.01). Thyroid stimulating hormone and CD8+initial T cells were positively correlated ( r=0.382, P<0.01). The proportion of B cells, cytotoxic T cells and suppressor T cells in CD8+cells of patients with complications [such as Graves orbitopathy (GO), thyroid toxic cardiomyopathy, etc.] was significantly different from that of the simple GD patients [18.3% (14.1%, 27.1%) vs 14.6% (10.8%, 21.4%), Z=2.54, P<0.05; 73.4%(65.6%,83.6%)vs 65.0%(50.3%,79.3%), Z=2.93, P<0.05; 26.6%(16.4%, 37.5%)vs 35.0%(20.7%,49.7%), Z=?2.74, P<0.05]. The proportion of suppressor T cells in GO patients was lower than that in non-GO patients [6.1% (3.4%, 8.1%) vs 8.5% (4.9%, 13.6%), Z=?3.20 P<0.05]. Conclusion:There are significant alterations in the circulating immune cells of GD patients, suggesting that immunological abnormalities play a crucial role in the onset and progression of the disease.

Objective:To evaluate the efficacy and safety of utilizing bicarbonate derived from the metabolism of regional citrate anticoagulation (RCA) as the sole base source for replacement fluid in continuous veno-venous hemofiltration (CVVH).Methods:A retrospective analysis was conducted on ICU patients who underwent RCA combined with CVVH between July 2024 and February 2025, with pre-treatment serum bicarbonate levels ranging from 18 mmol/L to 27 mmol/L. Patients managed with the "traditional RCA protocol" (4% citrate initially set at 1.2–1.5 times blood flow rate), using commercial calcium-containing replacement fluid (4 L/bag) with additional sodium bicarbonate supplementation, were assigned to the control group. Those treated with the "fixed RCA protocol" (targeting an extracorporeal citrate concentration of approximately 4 mmol/L), with a total effluent-to-citrate flow ratio of 9–10:1 and no supplemental sodium bicarbonate, were assigned to the study group. Outcomes included the incidence of metabolic acid-base disorders, amount of sodium bicarbonate used, filter lifespan, adverse events (e.g., bleeding), and 28-day mortality.Results:A total of 86 patients were enrolled, with 42 in the control group and 44 in the study group. The incidence of metabolic alkalosis was significantly higher in the control group (30.9%) than in the study group (2.3%) ( P < 0.001), while no significant difference was observed in the incidence of metabolic acidosis. Three patients in the study group received additional sodium bicarbonate during CVVH. The median sodium bicarbonate usage in the study group was 0 (0–5.6) mL, significantly lower than that in the control group [15.3 ( 8.3–24.3)] mL, P = 0.002). Filter lifespan was significantly shorter in the control group (36.4 ± 19.2 hours) compared to the study group (51.2 ± 17.6) h; P < 0.001]. Post-filter ionized calcium was significantly higher in the control group [(0.39 ± 0.08) mmol/L) than in the study group [(0.32 ± 0.09) mmol/L; P < 0.001]. CVVH was discontinued due to filter clotting in 71.4% of control patients, compared to 36.4% in the study group ( P < 0.05). In contrast, 45.5% of study group patients discontinued CVVH due to meeting treatment goals, versus only 9.5% in the control group ( P < 0.05). No treatment-related bleeding or citrate accumulation events occurred in either group. The 28-day mortality was 28.6% in the control group and 29.5% in the study group, with no statistically significant difference. Conclusions:In relatively stable patients, RCA can serve as a safe and effective independent base source for CVVH replacement fluid. This approach not only ensures adequate anticoagulation but also significantly reduces the incidence of metabolic alkalosis.

Objective:To explore the potential advantages and application prospects of cardiopulmonary resuscitation ventilation mode (CPRV) for ventilation during CPR, through comparing of the resuscitation effect of CPRV, intermittent positive pressure ventilation (IPPV) and impedance threshold device (ITD) during advanced cardiovascular life support (ACLS).Methods:30 miniature landrace pigs [weighing (31.7±4.5) kg] were randomly divided into three groups: CPRV group, IPPV group and ITD group (10 pigs in each group). Each animal received 5 min of chest compressions only CPR after 3 min of untreated ventricular fibrillation. Then in the ACLS stage, chest compressions and mechanical ventilation (tidal volume of 7 mL/kg, respiratory rate 10 times/min) were performed according to the divided groups. Defibrillation was delivered after 16 min of ACLS, and intravenous epinephrine was administered for the pigs without return of spontaneous circulation (ROSC). A second defibrillation was delivered after 2 more minutes of CPR. Blood gases, respiratory parameters, and hemodynamic parameters were collected at baseline, ACLS 8 min and ACLS 16 min. ROSC after defibrillation was also recorded.Results:At ACLS 8 min and 16 min, intrathoracic high pressure and intrathoracic pressure variability of CPRV group were significantly higher than those of IPPV and ITD group, while the absolute value of intrathoracic negative pressure in CPRV group was higher than that in IPPV group (all P <0.01), but no difference was found between CPRV group and ITD group. The levels of arterial pH, PaO 2 and venous oxygen saturation in CPRV group were significantly higher than those in IPPV group and ITD group during ACLS, while PaCO 2 was significantly lower in CPRV group than in IPPV group and ITD group (all P <0.05). Aortic blood pressure, coronary perfusion pressure and carotid blood flow during ACLS in CPRV group were significantly higher than those in IPPV group, and right atrial pressure of CPRV group was significantly lower than that of IPPV group (all P <0.05). Coronary perfusion pressure of CPRV group was significantly higher than that of ITD group at ACLS 16 min but not ACLS 8 min, and there were no differences of aortic blood pressure and carotid blood flow between CPRV group and ITD group. The total ROSC rate in the CPRV group (90%) was significantly higher than that in the IPPV group (30%) and the ITD group (40%) (P <0.05). Conclusion:Ventilation with CPRV during ACLS showed better ventilation, oxygenation, hemodynamic effects and higher ROSC than IPPV and ITD, and the use of CPRV during CPR shows a certain application prospect.

Objective:To retrospectively analyze the changes in the proportion of refined lymphocyte subsets in peripheral blood of patients with Graves disease (GD), and their correlation with the clinical characteristics and efficacy of GD, and to explore the immunological pathogenesis of Graves disease for seeking new therapeutic targets.Methods:A total of 97 newly diagnosed GD patients (GD group), 27 patients after treatment (treatment group), and 31 healthy individuals (control group) who visited the Fifth Medical Center of the PLA General Hospital from 2018 to 2021 were included in this study. The data of refined lymphocyte subsets, thyroid function, blood routine and clinical treatment of the three groups were compared and analyzed. The t-test and rank sum test were used to compare the proportions of lymphocyte subsets among different groups, and Pearson correlation analysis was used to analyze the correlation between the proportions of lymphocyte subsets and thyroid function indicators.Results:The proportion of B cells in GD group was higher than that in the control group [16.2%(11.8%, 21.8%) vs 10.2%(8.1%,13.6%)], while the proportion of natural killer (NK) cells was lower [9.4%(4.9%, 13.6%) vs 14.6%(12.1%,18.8%)], and the differences were statistically significant ( P<0.05). Abnormal T cell differentiation: the proportions of functional cells, including activated T cells, memory T cells, clustering antigen(CD)4+memory T cells, Th1 cells, and Tc1 cells, were lower than that in the control group [3.2%(2.1%, 5.7%) vs 5.8%(3.0%, 9.3%), P<0.05; 36.7% (29.9%, 48.1%) vs 48.0%(39.2%,57.7%), P<0.05; 23.1%(17.4%, 30.1%) vs 28.9%(23.3%,34.6%), P<0.05; 16.4% (11.8%, 23.6%) vs 24.3%(16.9%,28.5%), P<0.05; 28.5% (14.7%, 39.2%) vs 46.3%(21.6%,69.2%), P<0.05]. The proportion of activated T cells in the treatment group was higher than that in the GD group [6.5% (4.6%, 13.6%) vs 3.2% (2.1%, 5.7%), P<0.05]. The total triiodothyronine results showed positive correlations with B cells ( r=0.356, P<0.01) and negative correlations with NK cells ( r=?0.416, P<0.01), while the total thyroxine values showed negative correlations with NK cells and activated T cells ( r=?0.318,?0.335; P<0.01). Thyroid stimulating hormone and CD8+initial T cells were positively correlated ( r=0.382, P<0.01). The proportion of B cells, cytotoxic T cells and suppressor T cells in CD8+cells of patients with complications [such as Graves orbitopathy (GO), thyroid toxic cardiomyopathy, etc.] was significantly different from that of the simple GD patients [18.3% (14.1%, 27.1%) vs 14.6% (10.8%, 21.4%), Z=2.54, P<0.05; 73.4%(65.6%,83.6%)vs 65.0%(50.3%,79.3%), Z=2.93, P<0.05; 26.6%(16.4%, 37.5%)vs 35.0%(20.7%,49.7%), Z=?2.74, P<0.05]. The proportion of suppressor T cells in GO patients was lower than that in non-GO patients [6.1% (3.4%, 8.1%) vs 8.5% (4.9%, 13.6%), Z=?3.20 P<0.05]. Conclusion:There are significant alterations in the circulating immune cells of GD patients, suggesting that immunological abnormalities play a crucial role in the onset and progression of the disease.

Objective:To observe the clinical effect of Shenfu injection in preventing septic cardiomyopathy (SIC) in septic patients.Methods:From June 2022 to January 2023, patients with sepsis or septic shock who did not develop SIC were randomly divided into treatment group and control group according to the ratio of 1:1. In the treatment group, Shenfu injection (50 mL) was pumped intravenously once every 12 hours for 5 days. In the control group, 50 mL of normal saline was pumped intravenously once every 12 hours, and the course of treatment was 5 days. The primary end point was the incidence of SIC in the first 5 days. The secondary end points were the application time of vasoactive drugs, fluid balance in the previous week, hospitalization time in ICU, total ventilation time and 28-day mortality.Results:112 patients were randomly divided into two groups. Seven patients in the treatment group were excluded twice, and finally 49 patients were included in the analysis, while six patients in the control group were excluded twice and 50 patients included in the analysis. The total incidence of SIC in the treatment group within 5 days was significantly lower than that in the control group (42.9% vs. 64.0%, P = 0.035). Among them, the left ventricular systolic dysfunction in the treatment group was significantly lower than that in the control group (24.5% vs 52.0%, P=0.005), and there was no significant difference in the incidence of left ventricular diastolic dysfunction between the two groups. The incidence of right ventricular dysfunction in the control group was 28.0%, which was significantly higher than 10.2% in the treatment group ( P = 0.025). The duration of using vasoconstrictors in the treatment group was 75(48, 97) hours, which was significantly lower than 97(66, 28) hours in the control group ( P = 0.039). The duration of inotropic drugs use in the treatment group was 32(18, 49) h, which was also significantly shorter than 44(25, 61) h in the control group ( P=0.046). The fluid balance of the control group in the first week was (1 260±850) mL, which was significantly higher than (450±520) mL in the treatment group ( P=0.008). There was no statistical difference in ICU stay, total ventilation time and 28-day mortality between the two groups (all P > 0.05). Conclusion:Early application of Shenfu injection can significantly reduce the incidence of SIC, accompanied by less use of vasoactive drugs and positive fluid balance, which has a good clinical application prospect.

Inflammatory bowel disease(IBD)is an immune-mediated inflammatory disorder with high heterogeneity.The safety of its treatment,particularly adverse reactions,is a crucial area that physicians need to focus on.Currently,the biologic agents and small molecule drugs for treating IBD,such as anti-tumor necrosis factor-α agents,anti-integrin agents,interleukin(IL)-12/IL-23-targeting biologic agents,Janus kinase(JAK)inhibitors,and sphingosine-1-phosphate(S1P)receptor modulators,can induce both acute and chronic adverse reactions.Chronic adverse reactions mainly manifest as opportunistic infections,malignancies in different organs,especially lymphomas,as well as adverse reactions in the cardiovascular and nervous systems.The adverse reactions caused by the above-mentioned drugs exhibit both homogeneity and heterogeneity.Employing artificial intelligence(AI)techniques to summarize the patterns of biologic agents and small molecule drugs in the treatment of IBD and constructing models to predict the adverse reactions in heterogeneous individuals might be an important technological approach to enhance the safety of biologic treatments for IBD.This article reviews the research progress on the adverse reactions of biologic agents and small molecule drugs in the treatment of IBD.

Inflammatory bowel disease(IBD)is an immune-mediated inflammatory disorder with high heterogeneity.The safety of its treatment,particularly adverse reactions,is a crucial area that physicians need to focus on.Currently,the biologic agents and small molecule drugs for treating IBD,such as anti-tumor necrosis factor-α agents,anti-integrin agents,interleukin(IL)-12/IL-23-targeting biologic agents,Janus kinase(JAK)inhibitors,and sphingosine-1-phosphate(S1P)receptor modulators,can induce both acute and chronic adverse reactions.Chronic adverse reactions mainly manifest as opportunistic infections,malignancies in different organs,especially lymphomas,as well as adverse reactions in the cardiovascular and nervous systems.The adverse reactions caused by the above-mentioned drugs exhibit both homogeneity and heterogeneity.Employing artificial intelligence(AI)techniques to summarize the patterns of biologic agents and small molecule drugs in the treatment of IBD and constructing models to predict the adverse reactions in heterogeneous individuals might be an important technological approach to enhance the safety of biologic treatments for IBD.This article reviews the research progress on the adverse reactions of biologic agents and small molecule drugs in the treatment of IBD.

Ferroptosis, as a newly discovered cell death form, has become an attractive target for precision cancer therapy. Several ferroptosis therapy strategies based on nanotechnology have been reported by either increasing intracellular iron levels or by inhibition of glutathione (GSH)-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4). However, the strategy by simultaneous iron delivery and GPX4 inhibition has rarely been reported. Herein, novel tumor microenvironments (TME)-activated metal-organic frameworks involving Fe & Cu ions bridged by disulfide bonds with PEGylation (FCSP MOFs) were developed, which would be degraded specifically under the redox TME, simultaneously achieving GSH-depletion induced GPX4 inactivation and releasing Fe ions to produce ROS

Objective:To compare the therapeutic effects of nasal high-flow oxygen therapy (HFNC) and nasal canal oxygenation (NCO) during breaks off non-invasive ventilation (NIV) for acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and to explore the feasibility of NIV combined with HFNC in the treatment of AECOPD.Methods:From August 2017 to July 2019, AECOPD patients with type Ⅱrespiratory failure (arterial blood gas pH <7.35, PaCO 2 > 50 mmHg) who were treated with NIV were randomly (random number) assigned to the HFNC group and NCO group at 1:1. The HFNC group received HFNC treatment during breaks from NIV and the NCO group received low-flow NCO during the NIV interval. The primary endpoint was the total respiratory support time. The secondary endpoints were endotracheal intubation, duration of NIV treatment and breaks from NIV, length of ICU stay, total length of hospital stay and so on. Results:Eighty-two patients were randomly assigned to the HFNC group and the NCO group. After secondary exclusion, 36 patients in the HFNC group and 37 patients in the NCO group were included in the analysis. The total respiratory support time in the HFNC group was significantly shorter than that in the NCO group [(74 ± 18) h vs. (93 ± 20) h, P = 0.042]. The total duration of NIV treatment in the HFNC group was significantly shorter than that in the NCO group [(36 ± 11) h vs. (51 ± 13) h, P=0.014]. There was no significant difference of the mean duration of single break from NIV between the two groups, but durations of break from NIV in the HFNC group were significantly longer than those in the NCO group since the third break from NIV ( P < 0.05). The intubation rates of the HFNC and NCO groups were 13.9% and 18.9%, respectively, with no significant difference ( P=0.562). The length of ICU stay in the HFNC group was (4.3 ± 1.7) days, which was shorter than that in the NCO group [(5.8 ± 2.1) days, P=0.045], but there was no significant difference in the total length of hospital stay between the two groups. Heart rate, respiratory rate, percutaneous carbon dioxide partial pressure and dyspnea score during the breaks from NIV in the NCO group were significantly higher than those in the HFNC group, and the comfort score was lower than that in the HFNC group ( P<0.05). Conclusion:For AECOPD patients receiving NIV, compared with NCO, HFNC during breaks from NIV can shorten respiratory support time and length of ICU stay, and improve carbon dioxide retention and dyspnea. HFNC is an ideal complement to NIV therapy in AECOPD patients.

Objective To investigate the benefits and risks of stress ulcer prevention (SUP) using proton pump inhibitors (PPI) for critical patients. Methods The clinical data of adult critically ill patients admitted to the intensive care unit (ICU) of Northern Jiangsu People's Hospital from January 2016 to December 2018 were retrospectively analyzed. All patients who were treated with PPI for SUP within the first 48 hours after ICU admission were enrolled in the SUP group. Those who not received PPI were enrolled in the control group. A one-to-one propensity score matching (PSM) was performed to control for potential biases. The gender, age, underlying diseases, main diagnosis of ICU, drug use before ICU admission, sequential organ failure score (SOFA) at ICU admission, risk factors of stress ulcer (SU) and PPI usage were recorded. The end point was the incidence of gastrointestinal bleeding, hospital acquired pneumonia, Clostridium difficile infection and 30-day mortality. Kaplan-Meier survival curves were plotted, and survival analysis was performed using the log-rank test. Results 1 972 critical patients (788 in the SUP group and 1 184 in the control group) were enrolled, and each group enrolled 358 patients after PSM. Prior to PSM, compared with the control group, the SUP group had older patients, more underlying diseases, higher proportion of acute coronary syndrome (ACS), acute cerebrovascular disease, acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and poisoning in main diagnosis of ICU, more serious illness, and more risk factors of SU, indicating that ICU physicians were more likely to prescribe SUP for these patients. The incidence of gastrointestinal bleeding in the SUP group was significantly lower than that in the control group [1.8% (14/788) vs. 3.7% (44/1 184), P < 0.05], while the incidence of hospital acquired pneumonia and 30-day mortality were significantly higher than those in the control group [6.6% (52/788) vs. 3.5% (42/1 184), 17.9% (141/788) vs. 13.1% (155/1 184), both P < 0.01]. There was no significant difference in the incidence of Clostridium difficile infection between the SUP group and the control group [2.9% (23/788) vs. 1.8% (21/1 184), P >0.05]. After the propensity scores for age, underlying diseases, severity of illness and SU risk factors were matched, there was no significant difference in the incidence of gastrointestinal bleeding or 30-day mortality between the SUP group and the control group [2.2% (8/358) vs. 3.4% (12/358), 15.9% (57/358) vs. 13.7% (49/358), both P > 0.05], but the incidence of hospital acquired pneumonia in the SUP group was still significantly higher than that in the control group [6.7% (24/358) vs. 3.1% (11/358), P < 0.05]. Kaplan-Meier survival curve analysis showed that the 30-day cumulative survival rate of the SUP group was significantly lower than that of the control group before the PSM (log-rank test: χ2 = 9.224, P = 0.002). There was no significant difference in the 30-day cumulative survival rate between the two groups after PSM (log-rank test: χ2 = 0.773, P = 0.379). Conclusion For critical patients, the use of PPI for SUP could not significantly reduce the incidence of gastrointestinal bleeding and mortality, but increase the risk of hospital acquired pneumonia.