BACKGROUND:Periprosthetic osteolysis is the most common long-term complication of total joint arthroplasty.Many studies suggest that the inflammasome may play an important role during the osteolysis.Melatonin is a rhythm-regulated hormone secreted by the pineal gland with many functions including anti-inflammatory,anti-oxidation,and antitumor,but its effects on osteolysis and inflammasome have yet to be explored. OBJECTIVE:To explore the effect of melatonin on the osteolysis induced by wear particles and the role of melatonin on the activation of NLRP3 inflammasome. METHODS:(1)In vivo test:Fifteen C57BL/6 mice were randomly divided into sham operation group,osteolysis group and melatonin group by random number table method,with 5 mice in each group.The osteolysis model of the osteolysis group and the melatonin group was established by injecting cobalt-chromium-molybdenum(CoCrMo)particles into the sagittal suture of the skull.After injection,the melatonin group was intraperitoneally injected with 50 mg/(kg·d)of melatonin for 14 consecutive days.After drug intervention,the mouse calvarium was collected for micro-CT analysis to observe the micro-structural changes around the sagittal suture.(2)In vitro test:Mouse bone marrow-derived macrophages and THP-1 cells(which had been induced to differentiate into macrophages)were taken and divided into seven groups:normal group,lipopolysaccharide group,lipopolysaccharide+CoCrMo group and melatonin 0.5,1,1.5,2 mmol/L groups(lipopolysaccharide and CoCrMo were added to the melatonin intervention groups).After the intervention for 6 hours,the expression of related proteins(NLRP3,Caspase-1,interleukin-1β,and gasdermin D,gasdermin D-N terminal)in the inflammasome of cell lysate or cell culture supernatant was detected by western blot assay.Cytotoxicity and cell death were observed through lactate dehydrogenase release and live-dead fluorescence staining. RESULTS AND CONCLUSION:(1)In vivo test:Micro-CT scanning 3D reconstruction images showed that the bone mass around the sagittal suture of the skull of mice in the osteolysis group was significantly reduced,and the bone tissue structure was severely damaged.Compared with the osteolysis group,the bone mass around the sagittal suture of the skull in the melatonin group was significantly increased,and the destruction of tissue structure was reduced.(2)In vitro test:For mouse bone marrow-derived macrophages,lipopolysaccharide significantly up-regulated NLRP3 protein expression in cell lysate,and melatonin intervention could reduce NLRP3 protein expression in a dose-dependent manner.CoCrMo particles significantly up-regulated the protein expressions of the gasdermin D-N terminal in cell lysate and Caspase-1 and interleukin-1β in the supernatant of cell culture,while melatonin intervention could reduce the expression of these proteins in a dose-dependent manner.For THP-1 cells,the protein expressions of Caspase-1 and interleukin-1β in the supernatant of cell culture were significantly up-regulated by CoCrMo particles,and the expression of these proteins was decreased dose-dependent by melatonin intervention.Lactate dehydrogenase release and live-dead fluorescence staining showed that CoCrMo particles significantly increased the release of lactate dehydrogenase and cell death in the supernatant of mouse bone marrow-derived macrophage culture,and melatonin intervention could reduce the release of lactate dehydrogenase and cell death.(3)The results show that melatonin can inhibit particle-induced inflammasome activation and pyroptosis to suppress periprosthetic osteolysis.

Hematopoietic stem cell transplantation (HSCT) in children may lead to endothelial cell activation, and the induction of procoagulant, proinflammatory, and proapoptotic mediators, resulting in endothelial cell dysfunction and injury, as well as life-threatening complications.An effective management of endothelial cell activation, injury, and dysfunction is important for improving outcomes after HSCT.This article reviews the recent advances in the epidemiological features, pathogenesis and treatment of veno-occlusive disease/sinusoidal obstruction syndrome and transplant-related thrombotic microangiopathy after HSCT.

Objective:To investigate the clinical efficacy of laparoscopic radical resection of hilar cholangiocarcinoma (LRHCCA).Methods:The retrospective and descriptive study was constructed. The clinicopathological data of 211 patients who under LRHCCA in the Second Hospital of Hebei Medical University from May 2014 to June 2022 were collected. There were 135 males and 76 females, aged (63±8)years. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were described as absolute numbers or percentages. The Kaplan-Meier method was used to calculate survival rate and draw survival curve. Results:(1) Surgical situations. All 211 patients underwent LRHCCA successfully, with the operation time as 350 (300,390)minutes, volume of intraoperative blood loss as 400(200,800)mL, and intraoperative red blood cell transfusion as 2.0(range, 0-15.0)U, respectively. As partial portal vein invasion, 10 of 211 patients underwent portal vein resection and reconstruction. Results of intraoperative histopathology examination showed negative margin of portal vein. The operation time, volume of intraoperative blood loss, intraopera-tive red blood cell transfusion of the 10 patients was (400±53)minutes, 1 200(range, 800-3 000)mL, 5.5(range, 4.0-15.0)U, respectively. (2) Postoperative situations. Of the 211 patients, there were 63 cases of the Bismuth type Ⅰ, 65 cases of the Bismuth type Ⅱ, 22 cases of the Bismuth type Ⅲa, 26 cases of the Bismuth type Ⅲb, 35 cases of the Bismuth type Ⅳ. The R 0 resection rate was 95.73%(202/211). There were 202 patients identified as adenocarcinoma of the bile duct, including 7 cases with poorly differentiated tumor, 189 cases with moderate to poorly differentiated tumor, 3 cases with moderate to well differentiated tumor, 3 cases with well differentiated tumor. There were 8 patients with poorly differentiated biliary mucinous adenocarcinoma, 1 patient with intraductal papillary neoplasm with high-grade epithelial dysplasia. There were 24 cases of stage Ⅰ, 98 cases of stage Ⅱ, 30 cases of stage ⅢA, 34 cases of stage ⅢB, 19 cases of stage ⅢC, 6 cases of stage ⅣA. Of the 211 patients, there were 25 cases with postoperative biliary fistula, 11 cases with postoperative abdominal infection, 3 cases with postoperative bleeding as anastomotic bleeding after biliary fistula, 2 cases with postoperative gastric emptying disability, 1 case with postoperative acute liver failure. There were 7 patients undergoing postoperative unplanned reoperation, including 3 cases with emergency operation for hemostasis, 4 cases with abdominal exploration debridement and drainage for severe abdominal infection. There were 3 cases dead during perioperative period, including 1 case of acute liver failure, 1 case of systemic infection and multiple organ failure, 1 case of exfoliated deep venous thrombosis of lower extremities and acute pulmonary embolism. The postoperative duration of hospital stay was (15±5)days of the 211 patients and (17±4)days of patients undergoing portal vein resection and reconstruction. The cost of hospital stay of the 211 patients was (11.7±1.7)ten thousand yuan. (3) Follow-up. Of the 211 patients, 188 patients were followed up for 21(range, 4?36)months. The median survival time of 188 patients was 22 months, and the postoperative 1-, 2- and 3-year survival rate was 90.9%, 43.1% and 18.7%, respectively. Conclusion:LRHCCA is safe and feasible, with satisfactory short-term effect, under the coditions of clinicians with rich experience in laparoscopic surgery and patients with strict surgical evaluation.

Objective: To investigate the clinical presentation and genetic characteristics of malignant infantile osteopetrosis. Methods: This was a retrospective case study. Thirty-seven children with malignant infantile osteopetrosis admitted into Beijing Children's Hospital from January 2013 to September 2022 were enrolled in this study. According to the gene mutations, the patients were divided into the CLCN7 group and the TCIRG1 group. Clinical characteristics, laboratory tests, and prognosis were compared between two groups. Wilcoxon test or Fisher exact test were used in inter-group comparison. The survival rate was estimated with the Kaplan-Meier method and the Log-Rank test was used to compare the difference in survival between groups. Results: Among the 37 cases, there were 22 males and 15 females. The age of diagnosis was 0.5 (0.2, 1.0) year. There were 13 patients (35%) and 24 patients (65%) with mutations in CLCN7 and TCIRGI gene respectively. Patients in the CLCN7 group had an older age of diagnosis than those in the TCIRGI group (1.2 (0.4, 3.6) vs. 0.4 (0.2, 0.6) years, Z=-2.60, P=0.008). The levels of serum phosphorus (1.7 (1.3, 1.8) vs. 1.1 (0.8, 1.6) mmol/L, Z=-2.59, P=0.010), creatine kinase isoenzyme (CK-MB) (457 (143, 610) vs. 56 (37, 82) U/L, Z=-3.38, P=0.001) and the level of neutrophils (14.0 (9.9, 18.1) vs. 9.2 (6.7, 11.1) ×10⁹/L, Z=-2.07, P=0.039) at diagnosis were higher in the CLCN7 group than that in the TCIRG1 group. However, the level of D-dimer in the CLCN7 group was lower than that in the TCIRGI group (2.7 (1.0, 3.1) vs. 6.3 (2.5, 9.7) μg/L, Z=2.83, P=0.005). After hematopoietic stem cell transplantation, there was no significant difference in 5-year overall survival rate between the two groups (92.3%±7.4% vs. 83.3%±7.6%, χ²=0.56, P=0.456). Conclusions: TCIRGI gene mutations are more common in children with osteopetrosis. Children with TCIRGI gene mutations have younger age, lower levels of phosphorus, CK-MB, and neutrophils and higher level of D-dimer at the onset. After hematopoietic stem cell transplantation, patients with CLCN7 or TCIRGI gene mutations have similar prognosis.
Child ; Male ; Female ; Humans ; Osteopetrosis/therapy* ; Retrospective Studies ; Prognosis ; Genes, Recessive ; Phosphorus ; Chloride Channels/genetics* ; Vacuolar Proton-Translocating ATPases/genetics*

Objective:To investigate the prognosis of childhood adrenoleukodystrophy (ALD) with cognitive disorder after haploidentical allogenic hematopoietic stem cell transplantation (haplo-HSCT), and to identify risk factors affecting the prognosis.Methods:It was a single-center retrospective study involving 31 ALD children receiving haplo-HSCT in Peking University People′s Hospital from January 2014 to October 2022.Survival analysis was performed by Kaplan-Meier method. Cox regression analysis was performed to identify risk factors for the prognosis of childhood ALD following haplo-HSCT. Results:Among the 31 children with ALD, 1 case died of cardiogenic shock during the transplantation, and the remaining had a successful haplo-HSCT.Ten children with ALD had cognitive disorder before haplo-HSCT, including 3 cases with the minimal LOES score ≥10 points and 8 cases with the Neurologic Function Score (NFS)>0 point before haplo-HSCT.Six children had major functional disability (MFD) and 2 cases died due to progression of ALD after haplo-HSCT.Twenty children did not have cognitive disorder before haplo-HSCT, of whom 3 cases had the LOES score≥10 points and 6 cases had NFS>0 before haplo-HSCT.Four children had MFD and 2 cases died due to progression of ALD after haplo-HSCT.For ALD patients without cognitive disorder after haplo-HSCT, the 3-year and 5-year survival rate were 100.0% and 72.9%, respectively, and the 5-year MFD-free survival was 61.6%.For ALD patients with cognitive disorder after haplo-HSCT, the 3-year survival rate was 83.3%.Compared with ALD patients with the LOES score<10 points before haplo-HSCT, those with the LOES score≥10 points had 9.243 times the risk of developing MFD after haplo-HSCT ( P=0.024, 95% CI: 1.332-64.127). Compared with ALD patients without cognitive disorder before haplo-HSCT, ALD patients with cognitive disorder had 9.749 times the risk of developing MFD after haplo-HSCT ( P=0.023, 95% CI: 1.358-66.148). Conclusions:Cognitive disorder and LOES score≥10 points before haplo-HSCT are risk factors for developing MFD in children with ALD following haplo-HSCT.

Female ; Humans ; Melanoma/surgery* ; Neoplasms, Multiple Primary/pathology* ; Ovarian Neoplasms/pathology* ; Skin Neoplasms ; Teratoma/surgery*

This study aims to explore the factors influencing the success rate of the microdissection testicular sperm extraction (Micro-TESE) in patients with nonobstructive azoospermia (NOA) and cryptorchidism. Clinical data of 162 patients with cryptorchidism who underwent Micro-TESE due to infertility from December 2015 to May 2020 in the First Affiliated Hospital of Nanjing Medical University were analyzed retrospectively. In the univariate analysis, significant differences in the age of patient at the time of orchidopexy (median [interquartile range, IQR]: 7.0 [4.0-11.0] years vs 11.5 [9.0-14.5] years, P < 0.001), interval between orchidopexy and Micro-TESE (mean ± standard deviation: 17.5 ± 5.0 years vs 14.4 ± 4.4 years, P < 0.001), severity of cryptorchidism (unilateral [62.8%] vs bilateral [31.6%], P < 0.001; location of cryptorchidism, intra-abdominal [27.3%] vs inguinal [44.8%] vs suprascrotal [66.7%], P < 0.001), volume of the dominant testis (median [IQR]: 17.00 [15.00-19.00] ml vs 14.50 [11.75-16.25] ml, P < 0.001), and levels of follicle-stimulating hormone (FSH; P = 0.004) and testosterone (P = 0.006) were observed between the successful and failed sperm extraction groups. After conducting the multivariate analysis, four of these factors, including unilateral/bilateral cryptorchidism (P < 0.001), location of cryptorchidism (P = 0.032), age of orchidopexy (P < 0.001), and dominant testicular volume, were adopted in the clinical prediction model to evaluate preoperatively the success rate of Micro-TESE for patients with NOA and cryptorchidism. The likelihood of successful sperm retrieval by Micro-TESE in men with NOA and cryptorchidism increased in patients with mild forms of cryptorchidism.
Azoospermia ; Child ; Cryptorchidism ; Humans ; Male ; Microdissection ; Models, Statistical ; Prognosis ; Retrospective Studies ; Semen ; Sperm Retrieval ; Spermatozoa ; Testis

Objective:To analyze the plasma levels of soluble immune checkpoint molecules in patients with primary liver cancer and their prognostic significance.Methods:The levels of sCD28, sCD80, sCD137, sCD27, sGITR, sTIM3, sCTLA4, sHVEM, IDO, sLAG3, sBTLA, sPD1, sPDL1 and sPDL2 in plasma samples of 58 patients with primary liver cancer and 30 healthy controls were detected by liquid chip technology and compared between different groups. The relationship between the plasma levels of soluble immune checkpoint molecules and tumor recurrence was analyzed.Results:The levels of sCD28 and sCD80 were higher in patients in Barcelona Clinic Liver Cancer (BCLC) stage 0/A and B than in healthy controls and patients in BCLC-C stage ( P<0.05). However, the levels of sCD27 and sHVEM in BCLC-C patients were significantly lower than those in BCLC-0/A and BCLC-B patients, and even lower than healthy control group. The levels of sCD137, IDO and sPD1 in BCLC-0/A and BCLC-B patients were higher than those in healthy controls. The levels of sPDL1 and sPDL2 in different BCLC stages were all higher than those in healthy controls, and maintained at high level in the three stages, but there was no significant difference between different stages. After 24 months of interventional treatment, the preoperative sCD28 level was lower in patients with recurrent tumor recurrence than in patients without recurrence ( t=2.843, P=0.007). The optimal cut-off value of sCD28 based on the receiver operating characteristic (ROC) curve for predicting tumor recurrence was 101.42 pg/ml and the area under the ROC curve was 0.771 (95%CI: 0.611-0.931) with a sensitivity of 0.889 and a specificity of 0.666. The cumulative recurrence rate in patients with high sCD28 level (≥101.41 pg/ml) was 57.9% at 24 months after surgery, which was lower than the rate (95.5%) in patients with low sCD28 level (<101.41 pg/ml). The difference in the cumulative recurrence rate between the two groups was statistically significant (χ 2=15.777, P=0.000). Conclusions:The expression patterns of soluble immune checkpoint molecules varied in patients at different stages of primary liver cancer, suggesting that there were differences in their immune status and sCD28 could be used as a prognostic marker for postoperative recurrence of liver cancer.

Objective:To explore the classification and treatment strategies of developmental breast asymmetry (DBA).Methods:A retrospective study was conducted in adult female patients with developmental breast asymmetry deformity who underwent surgery between January 2005 to June 2019 in the Plastic Surgery Department of Peking Union Medical College Hospital. According to different clinical manifestations, DBA was divided into three types which adopted to different surgical strategies. Postoperative complications and patient satisfaction were evaluated.Results:A total of 203 patients were included in the study; 42.36% (86 cases) were type Ⅰ, 31.03% (63 cases) were type Ⅱ and 26.60% (54 cases) were type Ⅲ. The number of follow-up patients accounted for 79.3% (161/203). The mean follow-up time was 9 months. There were one case of poor healing of the axillary incision in latissimus dorsi muscle flap, two cases of seroma, five cases of Baker grade Ⅰ capsule contracture, two cases of Baker grade Ⅱ capsule contracture and one cases of small nodules in autologous fat breast augmentation. With regard to patient satisfaction, 80.1% (129 cases) felt satisfied with the aesthetic results, 15% (24 cases) felt good, 3.7%. (6 cases) felt average and 1.2% (2 cases) felt unsatisfied.Conclusions:This study shows that the clinical manifestations of DBA are varied, and our classification method is an effective and useful tool to guide the surgical treatment. Individualized surgical design is essential for aesthetical results.

Child ; Chronic Disease ; Epstein-Barr Virus Infections/complications* ; Familial Primary Pulmonary Hypertension/complications* ; Herpesvirus 4, Human ; Humans ; Persistent Infection ; Pulmonary Arterial Hypertension