BACKGROUND:The repair process of myocardial injury involves complex cellular and molecular mechanisms,especially mitochondrial calcium homeostasis,macrophage autophagy and pyroptosis pathways.Traditional Chinese medicine(TCM)has shown significant clinical efficacy in improving myocardial injury,but its mechanism of action needs to be thoroughly investigated. OBJECTIVE:To investigate the role of mitochondrial calcium homeostasis-mediated macrophage autophagy and pyroptosis pathways in myocardial injury,and to summarize the progress of TCM in this field. METHODS:A computerized search was performed for relevant literature from the database inception to March 2024 in the Web of Science,PubMed and CNKI.The search terms were"mitochondrial calcium homeostasis,macrophage autophagy,macrophage pyroptosis,traditional Chinese medicine,myocardial injury,myocardial injury reperfusion"in Chinese and English.Through literature review,we analyzed the relationship between mitochondrial calcium homeostasis and macrophage autophagy and pyroptosis,explored the mechanism of their roles in myocardial injury,and summarized the pathways of multi-targeted,multi-pathway effects of TCM. RESULTS AND CONCLUSION:The maintenance of mitochondrial calcium homeostasis has been found to be closely related to the normal function of cardiomyocytes.Macrophages can participate in the repair process of myocardial injury through autophagy and pyroptosis pathways.Autophagy contributes to cell clearance and regulation of inflammatory response,while pyroptosis affects myocardial repair by releasing inflammatory factors.TCM regulates mitochondrial calcium homeostasis and macrophage function through multiple mechanisms.For example,astragalosid regulates calcium homeostasis by lowering mitochondrial membrane potential and inhibiting cytochrome C,and epimedium glycoside plays a role in reducing β-amyloid deposition.In addition,herbal compounds and single drugs promote myocardial repair by activating or inhibiting specific signaling pathways,such as PI3K/AKT and nuclear factor-κB signaling pathways.Future studies should focus on the interactions between mitochondrial calcium homeostasis,autophagy and pyroptosis pathways,as well as how TCM can exert therapeutic effects through these pathways to provide new strategies and drugs for the treatment of myocardial injury.

OBJECTIVE To investigate the effects of esketamine for multimodal analgesia on opioid consumption and gastric motility in mechanically ventilated non-surgical intensive care unit （ICU） patients. METHODS Forty cases of mechanically ventilated non-surgical patients in the ICU of our hospital from February 1st， 2023 to July 31st， 2023 were selected and randomly divided into control group and esketamine （S-K） group using grouping method with opaque envelopes， with 20 cases in each group. Control group was given sufentanil， and S-K group was infused with Esketamine hydrochloride injection at a constant rate of 0.2 mg/（kg·h）+ sufentanil. The treatment period length， analgesic compliance rate， sedation level， analgesic and sedative consumption， and gastric motility indexes were compared between the two groups. RESULTS There was no statistically significant difference in the treatment period length， analgesic compliance rate， sedation level， or the consumption of propofol and midazolam between the two groups （P＞0.05）. The consumption of sufentanil in the S-K group was significantly less than control group （P＜ 0.05）. Compared with 1 h after randomization， the antral contraction frequency， antral contraction amplitude and antral motility index of patients in the S-K group were significantly higher at 72 h after randomization and were significantly higher than control group （P＜0.05）. CONCLUSIONS Esketamine may reduce opioid consumption and improve gastric motility in mechanically ventilated non-surgical ICU patients while ensuring a level of analgesic sedation.

Intra-abdominal infection is the second common infectious disease in intensive care unit and inhospital patients, with the mortality rate of 20%-30%. Advances in medicine have not improved the outcomes of patients with intra-abdominal infection, and the increasing multi-drug resistance organism may lead to a deterioration in the prognosis of patients with intra-abdominal infection. Gut microbiota dysbiosis and abdominal cavity infections show an interdependent and mutually aggravating relationship. Intestinal microecological preparations regulate gut flora and are potential therapeutic measures for intra-abdominal infections. The authors review the changes in gut flora during intra-abdominal infection, the effect of gut flora on the prognosis of intra-abdominal infections and the role of intestinal microecological preparations in intra-abdominal infections.

Objective:The purpose of this study is to determine the efficacy of haploidentical donor hematopoietic stem cell transplantation in the treatment of severe aplastic anemia.Methods:The clinical data of 76 patients with severe aplastic anemia (SAA) patients who underwent haplo-HSCT from December 2014 to October 2020 were selectively analyzed. There were 50 males and 26 females with a median age of 16 (3-52) years old. There were 49 SAA-Ⅰ patients, 18 SAA-Ⅱ patients, and 9 patients with hepatitis-associated aplastic anemia. There were 15 cases of bone marrow put together with peripheral blood stem cell transplantation and 61 cases of peripheral blood stem-cell transplantation. Conditioning regimens were Cyclophosphamide (CY) + Fludarabine (Flu) + ATG for 46 patients and Busulfan (Bu) + CY+Flu+ATG for 30 patients.Results:Three patients died during the myelosuppressive phase following transplantation, and 73 patients had a median time of neutrophil engraftment of 12 (9-21) days; in addition to 3 patients who died early, 8 patients did not obtain platelet reconstruction after transplantation, and 65 patients had platelet engraftment with a medium time of 14 (9-90) d. The incidence of primary graft failure was 10.9% and the incidence of secondary graft failure was 5.5%. The incidence of Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD) was 38.4%, the incidence of Ⅲ-Ⅳ aGVHD was 16.4%, the incidence of chronic graft anti-host disease (cGVHD) was 35.8%, and the incidence of extensive cGVHD was 22.4%. The medium follow-up time was 19.5 (1-75) months, the prospective overall survival (OS) for 2 years was (78.6±5.0) %, the failure-free survival (FFS) was (75.9±5.1) %, and the transplant-related mortality was (20.2±4.9) %. Multi-factor analysis revealed that the patient older than 35 years old, Ⅲ/Ⅳ aGVHD, HCT-CI≥3, the pre-transplant ferritin ≥1 500 μg/L, the number of neutrophils >1×10 9/L at the time of onset were risk factors affecting OS ( P=0.008, 0.008, 0.014, 0.004, 0.027) . Patients with graft failure had lower OS and FFS than other patients ( P<0.001) . Conclusion:Haplo-HSCT is an effective method for treating SAA in children, adolescents, and young patients, and the occurrence of severe aGVHD and severe infection, as well as graft failure, are the main causes of survival rate. The prevention and treatment of severe aGVHD and infection are essential to improve efficacy.

Objective: To evaluate the outcomes of myelodysplastic syndromes (MDS) patients who received HLA-matched sibling donor allogeneic peripheral blood stem cell transplantation (MSD-PBSCT) . Methods: The clinical data of 138 MDS patients received MSD-PBSCT from Sep. 2005 to Dec. 2017 were retrospectively analyzed, and the overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (RR) , non-relapse mortality (NRM) rate and the related risk factors were explored. Results: ①After a median follow-up of 1 050 (range 4 to 4 988) days, the 3-year OS and DFS rates were (66.6±4.1) % and (63.3±4.1) %, respectively. The 3-year cumulative incidence of RR and NRM rates were (13.9±0.1) % and (22.2±0.1) %, respectively. ②Univariate analysis showed that patients with grade Ⅲ-Ⅳ acute graft-versus-host disease (aGVHD) or hematopoietic cell transplantation comorbidity index (HCT-CI) ≥2 points or patients in very high-risk group of the Revised International Prognostic Scoring System (IPSS-R) had significantly decreased OS[ (42.9±13.2) %vs (72.9±4.2) %, χ²=8.620, P=0.003; (53.3±7.6) %vs (72.6±4.7) %, χ²=6.681, P=0.010; (53.8±6.8) %vs (76.6±6.2) %vs (73.3±7.7) %, χ²=6.337, P=0.042]. For MDS patients with excess blasts-2 (MDS-EB2) and acute myeloid leukemia patients derived from MDS (MDS-AML) , pre-transplant chemotherapy or hypomethylating agents (HMA) therapy could not improve the OS rate[ (60.4±7.8) %vs (59.2±9.6) %, χ²=0.042, P=0.838]. ③Multivariate analysis indicated that the HCT-CI was an independent risk factor for OS and DFS (P=0.012, HR=2.108, 95%CI 1.174-3.785; P=0.008, HR=2.128, 95%CI 1.219-3.712) . Conclusions HCT-CI was better than the IPSS-R in predicting the outcomes after transplantation. The occurrence of grade Ⅲ-Ⅳ aGVHD is a poor prognostic factor for OS. For patients of MDS-EB2 and MDS-AML, immediate transplantation was recommended instead of receiving pre-transplant chemotherapy or HMA therapy.

Objective:To compare the efficacy of autologous HSCT (auto-HSCT) with matched sibling donor (MSD) HSCT in Ph + ALL and provide a basis for the choice of transplantation method. Methods:We retrospectively investigated the outcomes of 78 adult patients with Ph + ALL who underwent auto-HSCT ( n=31) and MSD-HSCT ( n=47) in Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC, from January 2008 to December 2017. The overall survival (OS) rate, leukemia-free survival (LFS) rate, cumulative incidence of relapse (CIR) rate, nonrelapse mortality (NRM) rate, and the impact of achievement of complete molecular response (CMR) within 3 months and sustaining CMR up to transplantation (s3CMR) on transplantation method were explored. Results:The median time of neutrophil and platelet reconstitution in auto-HSCT and MSD-HSCT groups were 12 (10-29) days vs14 (11-24) days ( P=0.006) and 17.5 (10-62) days vs 7 (10-33) days ( P=0.794) , respectively. In the MSD-HSCT group, the incidence of Ⅱ-Ⅳ and Ⅲ-Ⅳ acute graft-versus-host disease (GVHD) was 27.7% (13/47) and 8.5% (4/47) , respectively. The incidence of limited and extensive chronic GVHD was 17.0% (8/47) and 12.8% (6/47) , respectively. The estimated CIR, NRM, LFS, and OS at 3 years were not significantly different between auto-HSCT and MSD-HSCT groups ( P>0.05) . For 44 patients who achieved s3CMR, 3-year OS[ (84.0±8.6) % vs (78.0±8.7) %, P=0.612], LFS[ (70.3±10.3) % vs (68.2±10.1) %, P=0.970], CIR[ (24.9±10.0) % vs (14.4±8.0) %, P=0.286], and NRM[ (4.7±4.7) % vs (17.4±8.1) %, P=0.209] of the auto-HSCT and MSD-HSCT groups were not significantly different. However, for 34 patients who did not reach s3CMR, 3-year cumulative relapse rate of patients in the auto-HSCT group was significantly higher than MSD-HSCT group[ (80.0±14.7) % vs (39.6±10.9) %, P=0.057]. Conclusions:auto-HSCT with maintenance therapy after HSCT appears to be an attractive treatment option for patients with Ph + ALL especially for those with s3CMR maintained up to transplantation. For non-s3CMR patients, allogeneic transplantation may be more effective from lower relapse.

Objective:To compare differences of autologous and unrelated donor stem cell transplantation (auto-HSCT and URD-HSCT) for adults with primary acute myeloid leukemia (AML) in first complete remission (CR 1) from a single center and to investigate the appropriate patients for the 2 types of transplant. Methods:In this retrospective investigation, we studied adults with primary AML who received auto-HSCT and URD-HSCT from March 2008 to November 2018. Overall survival (OS) , leukemia-free survival (LFS) , relapse, transplant-related mortality (TRM) , and hematopoietic reconstitution were compared along with the prognostic value of cytogenetics.Results:A total of 147 adult patients were enrolled in this study ( n=87 for auto-HSCT and n=60 for URD-HSCT) . Baseline characteristics were comparable between the 2 groups. The accumulative neutrophil engraftment rate at +30 days was not statistically different between the 2 groups[92.6% (95% CI 86.9%-98.3%) vs 98.3% (95% CI 95.0%-100.0%) , P=0.270], whereas the accumulative platelet engraftment rate at +60 days was significantly lower in the auto-HSCT group[83.6% (95% CI 75.8%-91.4%) vs 93.3% (95% CI 87.0%-99.6%) , P<0.001]. In patients undergoing URD-HSCT, the accumulative incidences of acute GVHD (aGVHD) and grade Ⅱ-Ⅳ aGVHD were 56.7% (95% CI 43.0%-68.2%) and 16.7% (95% CI 8.5%-27.2%) , and the incidences of chronic GVHD (cGVHD) and extensive cGVHD were 33.3% (95% CI 21.7%-45.4%) and 15.0% (95% CI 7.3%-25.2%) , respectively. After a median follow-up of 53.8 (0.8-127.8) months, patients in the 2 groups demonstrated comparable OS and LFS at 5 years after transplant[71.7% (95% CI 61.7%-81.7%) vs 67.8% (95% CI 55.8%-79.8%) , P=0.556; 64.6% (95% CI 54.4%-74.8%) vs 68.1% (95% CI 56.3%-79.9%) , P=0.642]. Patients in the auto-HSCT group showed significantly higher incidence of relapse at 5 years after transplant[31.9% (95% CI 22.2%-42.1%) vs 15.1% (95% CI 7.4%-25.6%) , P=0.015] and significantly lower incidence of TRM[3.4% (95% CI 0.9%-8.9%) vs 16.7% (95% CI 8.5%-27.2%) , P=0.006] compared with the URD group. HLA mismatching had no effects on the incidences of hematopoietic reconstitution, GVHD, OS, LFS, relapse, and TRM. Patients of cytogenetically favorable and intermediate risk demonstrated comparable OS and LFS after auto-HSCT and URD-HSCT, while patients of poor risk had significantly higher relapse and lower LFS after auto-HSCT. Conclusions:In this study, adults with primary AML in CR 1 demonstrated relatively higher relapse but lower TRM after auto-HSCT, resulting in comparable survival to that of URD-HSCT. In the absence of matched sibling donors, patients of cytogenetically poor risk should receive URD-HSCT in order to achieve lower relapse and better survival.

Objective:To explore the clinical characteristics, related factors, and prognostic effect of patients with T cell large granular lymphocytosis following allo-HSCT.Methods:Consecutive patients with T-LGL following allo-HSCT who visited our center from June 2013 to February 2020 were studied retrospectively. We compared patients undergoing allo-HSCT during this period. The clinical characteristics, related factors, cumulative incidence of patients with T-LGL and rates of overall survival (OS) , disease free survival (DFS) , relapse, and non-relapse mortality (NRM) were analyzed.Results:Total 359 patients were enrolled, including 17 with T-LGL and 342 without T-LGL following allo-HSCT. The median follow-up duration was 38 (3-92) month. The cumulative incidence at 1-, 2- and 3-years of T-LGL was 3.64% (95% CI 1.09%-6.19%) , 4.50% (95% CI 1.36%-7.64%) , and 4.84% (95% CI 1.10%-8.76%) , respectively. CMV reactivation ( P=0.013) , EB viremia ( P=0.034) , and aGVHD ( P=0.027) were associated with the development of T-LGL following allo-HSCT. Multivariate analysis showed that benign hematologic diseases[ P=0.027, OR=3.36 (95% CI 1.15-9.89) ] and haploidentical hematopoietic stem cell transplantation[ P=0.030, OR=4.67 (95% CI 1.16-18.75) ], unrelated donor transplantation[ P=0.041, OR=5.49 (95% CI 1.10-28.16) ] were independent predictive factors of T-LGL following allo-HSCT. There was a significant difference in the 3-year OS (100.0% vs. 78.6%, P=0.04) , DFS (100.0% vs. 70.0%, P=0.01) , and NRM (0 vs. 12.6%, P=0.02) between the 2 cohorts. Subgroup analysis showed that malignant diseases recipients who developed T-LGL had better outcomes after allo-HSCT, and there was a significant difference in the NRM ( P=0.042) , DFS ( P=0.013) , and cumulative relapse rate ( P=0.028) between the 2 cohorts. In contrast, the appearance of T-LGL after allo-HSCT in patients with benign diseases had no significant effect on the prognosis. Conclusions:T-LGL was a durable and clinically benign phenomenon occurring in allo-HSCT recipients with malignant diseases. Factors associated with immune reconstitution and T-cell regulatory mechanisms might be major predictors of T-LGL following allo-HSCT.

Objective: To investigate the clinical characteristics and outcomes of Maisonneuve fractures. Methods: Data of 21 cases of Maisonneuve fractures from February 2015 to December 2017 were retrospectively analyzed. There were 16 males and 5 females with an average age of 38.8 years (range, 21 to 61 years). The fractures occurred on the left side in 11 patients and on the right side in 10 patients. The causes of injuries were traffic accident in 4 patients, sprain injury in 9 patients and falling injury from height in 8 patients. There were 16 cases of medial malleolar fractures and 5 cases of ruptures of deltoid ligament (4 entirely and 1 partial). There were 17 cases of fractures of the posterior malleolus, among which there were 5 of typeⅠ, 8 of typeⅡ and 4 of type Ⅲ according to the Bartonícek classification of posterior malleolus. There were 4 cases without fracture of posterior malleolus including 1 complete disruption of posterior inferior tibiofibular ligament. Four cases were overlooked of Maisonneuve fracture at the first time. The interval between injury and operation was 2-12 days (mean, 4.9 days). Results: Stabilization of proximal fibular fractures were achieved with plate in 3 cases. There were 16 cases of medial malleolar fractures, and the fixation were achieved with cannulated screws in 13 cases and with anti-glide plates in 3 cases. The entirely rupture of deltoid ligament was repaired in 4 cases with suture anchors, the partial rupture of deltoid ligament was not repaired. There were 17 cases of posterior malleolar fractures, 12 cases treated with open reduction and internal fixation including cannulated screws in 9 cases and anti-glide plates in 3 cases. Stabilization of syndesmosis was achieved with syndesmotic plate in 1 case; the medial and posterior malleolar fractures were stabilized and anterior inferior tibiofibular ligament was repaired with suture anchor in 1 case; the other 19 cases were stabilized with syndesmotic screws, 2 screws in 11 cases and 1 screw in 8. Twenty-one patients were followed up for 13-48 months with an average of 25.6 months. The time of bony union was from 3 to 6 months with an average time of 4.9 months after operation. All patients received anatomical reduction without postoperative complications such as incision infection, reduction lose, breakage of screw and posttraumatic arthritis. In 13 cases, the syndesmotic screw was removed at the mean time of 15.38 weeks postoperative (range, 13-25 weeks). At the latest follow up, AOFAS score was from 84 to 100, with excellent in 13 cases, good in 8 cases, and the excellent and good rate was 100% (21/21). Baird-Jackson score was from 83 to 100, with excellent in 11 cases, good in 8 and fair in 2, and the excellent and good rate was 90.48%(19/21). Conclusion The diagnosis of proximal fibular fracture of Maisonneuve fracture is easily missed. The complete rupture of deep deltoid ligament and displaced obviously of posterior malleolar fracture should be reduction and stabilization. The accuracy of reduction of the syndesmosis is of great concern. The outcome of operation is satisfied.

Objective To explore the effect of iron overload on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) patiems with non-hepatitis related severe aplastic anemia (SAA).Methods The clinical data were retrospectively analyzed for 98 patients with non-hepatitis related SAA undergoing allo-HSCT from July 2012 to late July 2018 at a single center.Serum ferritin (SF) was measured within 2 momhs before HSCT.They were divided into iron overload (SF＞800.0 ng/ml,n =49) and control (SF＜800.0 ng/ml,n =49) groups according to SF level.Overall survival (OS),hematopoietic reconstitution and common complications after allo-HSCT were analyzed.Results The median pre-transplantation SF value was 798.7 (52.0-11060.01) ng/ml.Patients with pre-transplantation iron overload had a higher incidence of cytomegaloviremia (P =0.041),delayed recovery of neutrophil/platelet (P =0.001,P =0.005 respectively) and transfusion-dependence in donor-recipient blood group-matched patients (P =0.043) after allo-HSCT.The 3-year OS was (65.1 ± 7.1) ％ in iron overload group and (93.3 ± 3.7) ％ in control group (P =0.001).Multivariate analysis indicated that 3-year OS was independently correlated with pre-transplantation iron overload (P =0.022),blood group of donor & recipient (P =0.015),early bacteremia (P=0.003) and cytomegaloviremia (P =0.003).Conclusions Iron overload is common in patients with non-hepatitis-related SAA before transplantation.Pre-transplantation iron overload has a significant impact on OS,hematopoietic reconstitution and cytomegaloviremia after allo