BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

Objective To investigate the impact of not using drainage on clinical outcomes after arthroscopic autologous semitendinosus tendon reconstruction with anterior cruciate ligament reconstruction.Methods From March 2022 to June 2023,59 patients undergoing arthroscopic autologous semitendinosus tendon reconstruction with anterior cruciate ligament reconstruction in Lincang People's Hospital were collected and randomly divided into the non-drainage group consisting of 29 cases(observation group)and the 24-hour drainage group consisting of 30 cases(control group).The pain levels of the two groups of patients were recorded on the 1st,3rd,7th,14th,and 30th day after the surgery by using a visual analog scale.Additionally,the knee joint range of motion,length of hospital stay,and occurrence of postoperative complications were monitored.The circumference of the thigh was measured before and after the surgery,and the difference was calculated.Results Repeated measures analysis of variance revealed that there were statistically significant within-subject differences in pain ratings,thigh circumference,and knee joint range of motion(P<0.05),but no statistically significant between-subject differences(P>0.05).Independent samples t-tests showed that on the first day after the surgery,the observation group had lower pain ratings(P<0.001),and higher thigh circumference and knee joint range of motion compared to the control group(P<0.05).There were no statistically significant differences in pain ratings,knee joint range of motion,and thigh circumference between the two groups at the remaining follow-up times(P>0.05);The observation group had a shorter hospital stay than the control group(P<0.001);Both groups of patients had no complications such as lower limb nerve damage,deep vein thrombosis,knee joint infection,or hematomas requiring puncture and aspiration.Conclusion In the early postoperative period following arthroscopic autologous hamstring tendon reconstruction of the anterior cruciate ligament,the omission of drainage does not affect the clinical outcomes in terms of pain,knee joint mobility,and thigh circumference.Moreover,omitting drainage reduces the level of pain experienced by patients on the first day after the surgery,improves the knee joint mobility,and decreases the length of hospital stay.Therefore,in arthroscopic autologous hamstring tendon reconstruction of the anterior cruciate ligament,it is not recommended to routinely use drainage for preventive purposes.

Objective To establish a three-dimensional finite element model of knee joint in patients with mild knee osteoarthritis in the absence of CT and MRI with thin layer thickness,and to analyze the stress distributions of the tibial plateau.Methods A female patient with mild knee osteoarthritis was selected as the study object,and received serial CT scan from pelvis to distal tibia of fibula.The obtained files in DICOM format were imported into Mimics software for extracting the bony structures of knee joint through threshold segmentation,and then optimizing the extracted structures with Edit Masks,Cavity Fill and Region Grow.The generated model of bony structures was imported into 3-matic for smoothing and wrapping,and Geomagic Wrap was used for bony structure processing with mesh doctor inspection,surface defect repair and surface fitting.The cartilages,meniscus and ligaments were established by contour extension,and assembled with bony structures in SolidWorks in the way of origin coincidence.After defining material properties and contact relationships,meshing,and setting constraints and loads in ANSYS software,the stress distributions of the tibial plateau when standing with both legs were analyzed.Results A complete knee joint model including bony structure,cartilage and ligament was successfully established.When standing with two legs,the peak value of contact stress was about 1.21 MPa,and the maximum stress was 0.72 MPa at the medial middle of tibial plateau and lateral tibial plateau.The 62.7%and 37.3%of the total load were borne by the inner and outer compartments.Conclusion The model of the total knee joint is established with CT extraction and software rendering,and the finite element analysis results meet clinical expectations,indicating that the model established by the proposed method is reliable and can be used for follow-up research.

Bone substitute material implantation has become an important treatment strategy for the repair of oral and maxillofacial bone defects. Recent studies have shown that appropriate inflammatory and immune cells are essential factors in the process of osteoinduction of bone substitute materials. Previous studies have mainly focused on innate immune cells such as macrophages. In our previous work, we found that T lymphocytes, as adaptive immune cells, are also essential in the osteoinduction procedure. As the most important antigen-presenting cell, whether dendritic cells (DCs) can recognize non-antigen biomaterials and participate in osteoinduction was still unclear. In this study, we found that surgical trauma associated with materials implantation induces necrocytosis, and this causes the release of high mobility group protein-1 (HMGB1), which is adsorbed on the surface of bone substitute materials. Subsequently, HMGB1-adsorbed materials were recognized by the TLR4-MYD88-NFκB signal axis of dendritic cells, and the inflammatory response was activated. Finally, activated DCs release regeneration-related chemokines, recruit mesenchymal stem cells, and initiate the osteoinduction process. This study sheds light on the immune-regeneration process after bone substitute materials implantation, points out a potential direction for the development of bone substitute materials, and provides guidance for the development of clinical surgical methods.
Biocompatible Materials/metabolism* ; HMGB1 Protein/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Bone Substitutes/metabolism* ; Dendritic Cells/metabolism*

OBJECTIVES: Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are common operative neurocognitive disorders, which places a heavy burden on patients, families and society. Therefore, it is very important to search for preventive drugs. Previous studies have demonstrated that perioperative use of dexmedetomidine resulted in a decrease the incidence of POD and POCD. But the specific effect of dexmedetomidine on elderly patients undergoing hepatic lobectomy and its potential mechanism are not clear. This study aims to evaluate the efficacy of intraoperative use of dexmedetomidine on preventing POD and POCD in elderly patients undergoing hepatic lobectomy and the influence on the balance between proinflammation and anti-inflammation. METHODS: This trial was designed as a single-center, prospective, randomized, controlled study. One hundred and twenty hospitalized patients from January 2019 to December 2020, aged 60-80 years old with American Society of Anesthesiologists (ASA) II-III and scheduled for hepatic lobectomy, were randomly allocated into 3 groups (n=40) using a random number table: A C group, a Dex1 group, and a Dex2 group. After anesthesia induction, saline in the C group, dexmedetomidine [0.3 μg/(kg·h)] in the Dex1 group, and dexmedetomidine [0.6 μg/(kg·h)] in the Dex2 group were infused until the end of operation. The incidences of hypotension and bradycardia were compared among the 3 groups. Confusion Assessment Method (CAM) for assessing POD and Mini Mental State Examination (MMSE) for evaluating POCD were recorded and venous blood samples were obtained for the determination of neuron specific enolase (NSE), TNF-α, IL-1β, and IL-10 at the different time below: the time before anesthesia (T0), and the first day (T1), the third day (T2), the fifth day (T3), and the seventh day (T4) after operation. RESULTS: Compared with the C group, the incidences of bradycardia in the Dex1 group or the Dex2 group increased (both P<0.05) and there was no difference in hypotension in the Dex1 group or the Dex2 group (both P>0.05). The incidences of POD in the C group, the Dex1 group, and the Dex2 group were 22.5%, 5.0%, and 7.5%, respectively. The incidences of POD in the Dex1 group or the Dex2 group declined significantly as compared to the C group (both P<0.05). However, there is no difference in the incidence of POD between the Dex1 group and the Dex2 group (P>0.05). The incidences of POCD in the C group, the Dex1 group, and the Dex2 group were 30.0%, 12.5%, and 10.0%, respectively. The incidences of POCD in the Dex1 group and the Dex2 group declined significantly as compared to the C group (both P<0.05). And no obvious difference was seen in the incidence of POCD in the Dex1 group and the Dex2 group (P>0.05). Compared with the C group, the level of TNF-α and IL-1β decreased and the level of IL-10 increased at each time points (from T1 to T4) in the Dex1 group and the Dex2 group (all P<0.05). Compared with the Dex1 group, the level of IL-1β at T2 and IL-10 from T1 to T3 elevated in the Dex2 group (all P<0.05). Compared with the T0, the concentrations of NSE in C group at each time points (from T1 to T4) and in the Dex1 group and the Dex2 group from T1 to T3 increased (all P<0.05). Compared with the C group, the level of NSE decreased from T1 to T4 in the Dex1 group and the Dex2 group (all P<0.05). CONCLUSIONS Intraoperative dexmedetomidine infusion can reduce the incidence of POCD and POD in elderly patients undergoing hepatic lobectomy, and the protective mechanism appears to involve the down-regulation of TNF-α and IL-1β and upregulation of IL-10 expression, which lead to rebalance between proinflammation and anti-inflammation.
Aged ; Aged, 80 and over ; Bradycardia ; Cognitive Dysfunction/prevention & control* ; Delirium/prevention & control* ; Dexmedetomidine/therapeutic use* ; Humans ; Hypotension/drug therapy* ; Interleukin-10 ; Middle Aged ; Postoperative Cognitive Complications/prevention & control* ; Postoperative Complications/epidemiology* ; Prospective Studies ; Tumor Necrosis Factor-alpha

Objective:To investigate the effects of antibiotic treatment and antibiotics combined with surgery treatment on the prognosis of patients with infective endocarditis (IE).Methods:The clinical data and prognosis of all patients diagnosed as IE discharged from Shanghai Jiao Tong University Affiliated Sixth People′s Hospital from June 2011 to May 2021 were collected. There were 240 IE patients, divided into antibiotic treatment group and the antibiotics combined with surgery group according to the treatment methods. The clinical characteristics and prognosis of the IE patients were compared between the two groups, so as to investigate the timing of surgery for IE patients and to analyze the effects of the two treatment methods on the prognosis of IE patients.Statistical analysis methods including Wilcoxon rank sum test, chi-square test, Kaplan-Meier survival analysis and Cox regression analysis were used when appropriate.Results:Of the 240 patients with IE, 63 cases were only treated with antibiotics and 177 cases were treated with antibiotics combined with surgery. After propensity score matching (PSM), one-year mortality rate of the IE patients in the antibiotics combined with surgery group was 11.1%(4/36), which was significantly lower than that in the antibiotic treatment group (33.3%(12/36), χ2=5.14, P=0.023). The median values of left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD) and left ventricular fractional shortening (LVFS) in the antibiotics combined with surgery group were 59%, 47 mm and 31%, respectively, which were significantly lower than those before surgery (63%, 54 mm and 34%, respectively, Z=6.19, 9.36 and 6.11, respectively, all P<0.001). The most common surgical indication was moderate to severe heart failure, and there was no significant difference between the early operation group and the late operation group (both P>0.050). The one-year cumulative survival rate of antibiotics combined with surgery group was 94.9%, which was significantly higher than that in the antibiotic treatment group (83.2%, χ2=7.38, P=0.007). Heart failure and Pitt bacteremia scores≥4 were the independent risk factors for one-year all-cause death of the IE patients (hazard ratio ( HR)=5.668 and 19.392, respectively, both P<0.050). Hospital days and antibiotics combined with surgery were independent related factors for reducing the risks of one-year all-cause death ( HR=0.931 and 0.299, respectively, both P<0.050). Pitt bacteremia scores≥4 had the greatest impact on one-year prognosis of the IE patients. Conclusions:Surgery could significantly improve cardiac function and one-year prognosis of the IE patients. IE patients with heart failure and Pitt bacteremia score≥4 should be actively treated.

Objective:To clarify the effect of ubiquitination hepatitis B virus core antigen (Ub-HBcAg) on dendritic cells (DC) autophagy, and to explore the mechanism of autophagy in enhancing DC antigen presentation and inducing hepatitis B virus-specific cytotoxic T lymphocyte (CTL) responses.Methods:Ub-HBcAg lentiviral vector (LV-Ub-HBcAg), lentiviral vector-hepatitis B virus core antigen (LV-HBcAg) and no-load plasmid LV (LV) were constructed and packaged. DC2.4 cells were divided into LV-Ub-HBcAg group, LV-HBcAg group and LV group. The blank control group (NC group) was also set. The protein expression of autophagy-related protein P62, microtubule associated protein 1 light chain 3 beta (LC3B), autophagy related 5(ATG5) and Beclin-1 were detected by Western blotting. The expressions of co-stimulatory molecules such as CD86, CD80 and major histocompatibility complex (MHC)-Ⅱ were detected by flow cytometry. Cell counting kit-8 (CCK-8) method was used to detect T lymphocytes proliferation. The non-radioactive lactic acid dehydrogenase (LDH) release method was applied to detect the killing ability of CTL. Statistical analysis was conducted by independent sample t test. Results:The relative protein expressions of LC3B-Ⅱ/LC3B-Ⅰ, Beclin-1 and ATG5 in NC group were 0.445±0.076, 0.522±0.026 and 0.761±0.038, respectively, which were all lower than those in LV-Ub-HBcAg group (0.926±0.021, 0.919±0.016 and 1.451±0.028, respectively). The relative protein expression of P62 in the NC group was higher than that in LV-Ub-HBcAg group ((1.875±0.016) vs (0.647±0.121)). The differences were all statistically significant ( t=6.102, 9.842, 17.490 and 10.590, respectively, all P<0.01). The expressions of CD86 (75.51%), CD80 (83.35%), MHC-Ⅱ (66.66%) in the LV-Ub-HBcAg group were high, and those in the NC group were 8.03%, 7.49%, 0.04%, respectively. The specific CTL killing rate ((65.310±2.091)%) of the LV-Ub-HBcAg group was significantly higher than both NC group ((14.400±0.497)%) and LV-HBcAg group ((54.870±1.443)%), and the differences were both statistically significant ( t=23.690 and 4.111, respectively, both P<0.05). Conclusion:Ub-HBcAg promotes the DC autophagy, up-regulates the expressions of costimulatory molecules on cell surface of DC to induce the maturation and activation, and then stimulates T lymphocyte to induce a stronger specific CTL response under the effort of ubiquitination.

AIM: To synthesize

Objective:To evaluate the clinical value of suspensory incision and suture technique in endoscopic full-thickness resection (EFTR) for muscularis propria tumor of gastric fundus.Methods:A retrospective analysis was performed on the data of 20 patients with muscularis propria tumor in gastric fundus and undergoing EFTR in the First Medical Center of PLA General Hospital from June 2017 to June 2019. Patients were divided into the observation group (9 cases) treated with suspensory incision and suture technique in EFTR and the control group (11 cases) treated with traditional EFTR method. The baseline data and perioperative data of the two groups were analyzed.Results:EFTR was successfully performed on all 20 patients. The tumor size of the observation group and the control group was 10.0 (7.5, 21.0) mm and 14.0 (10.0, 20.0) mm, respectively. The resection time of the two groups was 26.4±6.3 min and 35.5±11.4 min, respectively. The postoperative hospital stay was 6.4±1.0 d and 7.7±1.5 d, respectively. No postoperative delayed bleeding, perforation, or other complications occurred in the two groups.Conclusion:Using suspensory incision and suture technique is safe and effective during EFTR for muscularis propria tumor in gastric fundus, and can reduce operation time. This technique is worth applying in clinic.

Objective Tamm-Horsfall protein (THP) may play a role in kidney stone formation.The article aimed to conduct a preliminary study on the role of THP in kidney stone formation by investigating the changes of THP in rat urine, pathological changes of renal tissue and the formation of calcium salt crystals after establishing CNPs rat model of kidney stones.Methods Stone samples of 40 patients from February to June 2015 in our department were collected to establish the model of CNPs-induced kidney stone in rats and prepare CNPs suspension.48 SD rats were randomly divided into experimental group (group A) and blank control group (group B).Group A were injected with CNPs and the same amount of sterile saline injection in the group B.The urine of rats was collected after injection at 3h, 6h, 12h, 24h, 1w, 2w, 4w and 8w.ELISA were applied to detect THP levels in the urine.Then the rats were killed to take the kidney tissue.HE staining was used to investigate the pathological changes of the cells and evaluate the formation of the calcium salt crystals.Results THP levels in group A at 24h, 1w, 2w, 4w and 8w ([166.03±3.02], [173.50±1.78], [174.55±2.05], [176.54±2.45], [177.11±1.76]pg/mL) were significantly higher than that at 3h(165.89±2.23pg/mL)(P<0.05), which was the same case in comparison with those of group B ([157.65±2.22], [156.54±1.43], [159.45±3.21], [158.63±2.98], [157.33±2.05]pg/mL).Compared with the calcium salt crystal score at 6h (1 point), the scores at 3,6,12,24h (average score 2 points) increased.At 2w the score increased significantly to 3 points and reached the top score(6.7points) at 8w, which was of significant difference.The score of calcium salt crystals was in positive correlation with THP content (r=0.843,P<0.05).Conclusion THP in urine may contribute to the aggregation of calcium salt crystals and the formation of kidney stones.