Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective: To analyze the efficacy, safety, and long-term prognosis of intermediate-dose cytarabine (Ara-c) regimen in the treatment of children with refractory risk organ involvement Langerhans cell histiocytosis (LCH). Methods: Clinical data of 17 children with multisystem and risk organ involvement LCH who failed the first-line therapy and were treated with intermediate-dose Ara-c (250 mg/m², twice daily) regimen in the Hematology Center, Beijing Children's Hospital from January 2013 to December 2016 were analyzed retrospectively. In addition to the basic treatment of vindesine and dexamethasone, the patients received two regimens: regimen A: the intermediate-dose Ara-c combined with cladribine and regimen B: the intermediate-dose Ara-c alone. The efficacy, safety and prognosis of the two regimens were analyzed. Results: Among all 17 patients, there were 11 males and 6 females, with the diagnosis age of 2.1 (1.6, 2.7) years. Ten children received regimen A, all of them achieved active disease-better (AD-B) after 8 courses of induction therapy. The disease activity scores (DAS) decreased from 5.5 (3.0, 9.0) to 1.0 (0, 2.3). Seven children received regimen B, and 6 of them achieved AD-B after 8 courses of induction therapy. The DAS decreased from 4.0 (2.0, 4.0) to 1.0 (0, 2.0). The follow-up time was 6.2 (4.9,7.2) and 5.2 (3.7,5.8) years in group A and B. The 5-year overall survival rate was 100.0% in both groups, and the 5-year event free survival rate was (88.9±10.5)% and (85.7±13.2)% in group A and B. Grade 3 or 4 myelosuppression was observed in 8 patients in group A and 2 patients in group B. Conclusions: The intermediate-dose Ara-c regimen (with or without cladribine) is effective and safe for patients with refractory high-risk LCH, with a good long-term prognosis.
Male ; Female ; Child ; Humans ; Cytarabine/adverse effects* ; Cladribine/adverse effects* ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Histiocytosis, Langerhans-Cell/drug therapy* ; Prognosis

Peripheral bacterial infections without impaired blood-brain barrier integrity have been attributed to the pathogenesis of Parkinson's disease (PD). Peripheral infection promotes innate immune training in microglia and exacerbates neuroinflammation. However, how changes in the peripheral environment mediate microglial training and exacerbation of infection-related PD is unknown. In this study, we demonstrate that GSDMD activation was enhanced in the spleen but not in the CNS of mice primed with low-dose LPS. GSDMD in peripheral myeloid cells promoted microglial immune training, thus exacerbating neuroinflammation and neurodegeneration during PD in an IL-1R-dependent manner. Furthermore, pharmacological inhibition of GSDMD alleviated the symptoms of PD in experimental PD models. Collectively, these findings demonstrate that GSDMD-induced pyroptosis in myeloid cells initiates neuroinflammation by regulating microglial training during infection-related PD. Based on these findings, GSDMD may serve as a therapeutic target for patients with PD.

Objective: To evaluate the efficacy and safety of Beijing Children's Hospital (BCH) modified hemophagocytic lymphohistiocytosis (HLH) 04 regimen in the treatment of childhood HLH. Methods: A retrospective cohort study was conducted. From January 2016 to December 2017, 110 children with HLH who were treated with the modified HLH-04 regimen (replacing dexamethasone with methylprednisolone during the induction period, reducing the dose and frequency of etoposide, and not using cyclosporine except for autoimmune-related HLH) at the Hematology Oncology Center of Beijing Children's Hospital were selected as the modified group, while 102 children treated with the standard HLH-04 regimen from January 2012 to December 2015 were selected as the control group. The early remission rate, survival rate and adverse reactions of two groups were compared. Rank sum test and chi square test were used for comparison between groups. Results: The age of onset in the modified group was 1.9 (1.1, 3.5) years, with 65 males and 45 females. The age of onset in the control group was 2.0 (1.2, 4.6) years, with 47 males and 55 females. No significant difference was found in age and gender between 2 groups (both P>0.05). Except for fibrinogen (1.3 (1.0, 1.7) vs. 1.1 (0.8, 1.4) g/L, Z=-2.67, P=0.008) and natural killer cell activity (13.9 (13.4, 16.3) % vs.14.9 (12.0, 16.1) %, Z=-2.34, P=0.028), there were no statistically significant differences in etiology, disease duration, first clinical presentation, or laboratory tests between 2 groups (all P>0.05). At 2 months and 3 years, there were no statistically significant differences in overall survival between 2 groups (84.5% (93/110) vs.76.5% (78/102), 78.2% (86/110) vs. 67.6% (69/102), χ²=2.28, 3.07, P=0.131, 0.080). The first 3 weeks were the most common time for bone marrow suppression in the modified group, with a lower incidence than in the control group (47.3% (52/110) vs. 62.7% (64/102), χ²=5.11, P=0.024). The modified group had a lower rate of fungal infections than the control group (3.6% (4/110) vs. 13.7% (14/102), χ²=6.93, P=0.008). Compared with the control group, fewer children in the modified group died as a result of side effects from chemotherapy (8.0% (2/25) vs.30.3% (10/33), χ²=4.31, P=0.038). Conclusion: The BCH modified HLH-04 regimen reduced the intensity of chemotherapy, with overall efficacy no worse than the standard HLH-04 regimen, and significantly reduced the rate of chemotherapy-related myelosuppression, fungal infection and mortality.
Child ; Cyclosporine/therapeutic use* ; Etoposide ; Female ; Hospitals ; Humans ; Lymphohistiocytosis, Hemophagocytic/etiology* ; Male ; Retrospective Studies

No consensus on standardized technique of enterostomy creation has been made meanwhile high heterogeneity of surgical procedure exists in 'stoma creation' chapters of textbooks or atlases of colorectal surgery. The present article reviews the anatomy of tendinous aponeurotic fibers which is crucial for abdominal wall tension and integrity. Through empirical practice we hypothesize a procedure of enterostomy creation basied on abdominal wall tension plus anchor suture for fascia fixation which could theoretically decrease short-term stoma complication rates and long-term parastomal hernia rates. Surgical techniques are as followed: (1) preoperative stoma site mark for de-functioning ileostomy should be positioned at the lateral border of rectus abdominis muscle (RAM) to decrease the difficulty of stoma reversal and for permanent colostomy should be placed overlying the RAM to promote adhesion; (2)Optimal circular removal or lineal opening of skin, and avoid dissection of subcutaneous tissue; (3) Lineal dissection of natural strong fascia (rectus sheath) at stoma site and blunt separation of muscular fibers. The tunnel of the fascia should be made with appropriate size without undue tension. To prevent the formation of dead space, additional suturing at fascia layer is unnecessary. (4) Anchor suture for fascia fixation at two ends of fascia opening could be considered to avoid delayed fascia disruption and parastomal hernia. (5) After pull-through of ileum or colon loop, 4-8 interrupted seromuscular sutures could be placed to attach loop to skin. For ileostomy, self-eversion of mucosa can be successful in vast majority of cases and a Brooke ileostomy is not necessary. The efficacy and safety of this procedure should be tested in future trials.
Humans ; Abdominal Wall/surgery* ; Surgical Stomas/adverse effects* ; Enterostomy ; Incisional Hernia ; Fascia

Group A Streptococcus (GAS) is a very important pathogen, especially for children.On a global scale, GAS is an important cause of morbidity and mortality.But the burden of disease caused by GAS is still unknown in China and also has not obtained enough attention.For this purpose, the expert consensus is comprehensively described in diagnosis, treatment and prevention of GAS diseases in children, covering related aspects of pneumology, infectiology, immunology, microbiology, cardiology, nephrology, critical care medicine and preventive medicine.Accordingly, the consensus document was intended to improve management strategies of GAS disease in Chinese children.

Objective:To analyze the results of plague surveillance in Qinghai Province from 2011 to 2020, master the epidemic situation in recent years, and provide scientific basis for prevention and control of the plague in the future.Methods:The human plague epidemic data (from the human case database of Qinghai Institute for Endemic Disease Prevention and Control) and animal plague epidemic data (from plague monitoring data and plague focus survey data of Qinghai Province) from 2011 to 2020 were collected and analyzed with descriptive epidemiological methods, including human plague epidemic, animal plague epidemic regional distribution, host animal monitoring results, pathogenic monitoring results and serological monitoring results.Results:From 2011 to 2020, there was a human plague epidemic in Qinghai Province, which was infected due to the infection of a middle finger of the right hand that was accidentally scratched when peeling marmots, and Yersinia pestis was isolated from heart, liver, lung, lymph node puncture fluid, tracheal secretion and throat swab samples of the deceased. There were 16 animal plague epidemics and endemic areas were distributed in Haixi Prefecture, Yushu Prefecture and Haibei Prefecture, among which the animal plague epidemic was the most prevalent in Haixi Prefecture, with 13 outbreaks in recent 10 years. According to the monitoring of host animals, the main host animal was the Himalayan marmot, with an average density of 0.07/hm 2. Pathgenic monitoring showed that 31 strains of Yersinia pestis were isolated, of which 27 strains were isolated from Haixi Prefecture. The host animals of Yersinia pestis were mainly Himalayan marmot, accounting for 77.42% (24/31) of the total. Serological monitoring showed that 66 plague F1 antibody positive sera were detected, of which 43 were dog positive sera; the Himalayan marmot took the second place, 20. Conclusion:From 2011 to 2020, the animal plague in Qinghai Province has continued for many years, with some areas showing an active trend, and the overall situation of plague prevention and control is severe.

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

Purpose: We sought to investigate the effectiveness and safety of dabrafenib in children with BRAFV600E-mutated Langerhans cell histiocytosis (LCH). Materials and Methods: A retrospective analysis was performed on 20 children with BRAFV600E-mutated LCH who were treated with dabrafenib. Results: The median age at which the patients started taking dabrafenib was 2.3 years old (range, 0.6 to 6.5 years). The ratio of boys to girls was 2.3:1. The median follow-up time was 30.8 months (range, 18.9 to 43.6 months). There were 14 patients (70%) in the risk organ (RO)+ group and six patients (30%) in the RO– group. All patients were initially treated with traditional chemotherapy and then shifted to targeted therapy due to poor control of LCH or intolerance to chemotherapy. The overall objective response rate and the overall disease control rate were 65% and 75%, respectively. During treatment, circulating levels of cell-free BRAFV600E (cfBRAFV600E) became negative in 60% of the patients within a median period of 3.0 months (range, 1.0 to 9.0 months). Grade 2 or 3 adverse effects occurred in five patients. Conclusion Some children with BRAFV600E-mutated LCH may benefit from monotherapy with dabrafenib, especially high-risk patients with concomitant hemophagocytic lymphohistiocytosis and intolerance to chemotherapy. The safety of dabrafenib is notable. A prospective study with a larger sample size is required to determine the optimal dosage and treatment duration.

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*