OBJECTIVE To explore the safety and efficacy of tocilizumab in the treatment of refractory anti-N-methyl-D-aspartate receptor encephalitis in children, and to provide reference for the treatment of this disease. METHODS The clinical manifestations, diagnosis and treatment, safety and efficacy of tocilizumab in a case of refractory anti-NMDAR encephalitis in Children’s Hospital, Zhejiang University School of Medicine were analyzed retrospectively, and the relevant literature was reviewed. RESULTS The clinical symptoms of the patient were not improved after 2 doses of methylprednisolone, immunoglobulin and 6 doses of rituximab. After 6 doses of tocilizumab, the modified Rankin scale(mRS) score was improved without adverse reactions. CONCLUSION Tocilizumab, as a escalation second-line immunotherapy, is effective and well tolerated in the treatment of refractory anti-NMDAR encephalitis. It is one of the potential therapeutic means.

Objective To explore the effect of a phased rehabilitation training programme to relieve shoulder dys-function in patients after neck dissection and to provide effective solutions for postoperative shoulder joint function recov-ery of patients.Methods This study has been reviewed and approved by the Ethics Committee,and informed consent has been obtained from patients.A phased rehabilitaiton training programme for the shoulder after neck dessection was developed through literature review and discussion,and 70 eligible patients from Hospital of Stomatology,Sun Yat-sen University from December 2020 to April 2021 were selected and randomly divided into the test group and control group(35 patients in each group).The control group underwent motor rehabilitation training from 6 weeks postoperative to 1 year after surgery,such as shoulder mobility and coordination training and small range of motion training of the neck,while the test group took part in a rehabilitation training program that included familiarization maneuver training,protective rehabilitation,exercise rehabilitation,and resistance training in the following four stages:preoperative,postop-erative general anesthesia and awake until the removal of stitches,the removal of stitches until 6 weeks after surgery,and 6 weeks after surgery until 1 year after surgery.The frequency of training in both groups was at least 3 days per week,and the length of each training session was 10-15 min.The intensity of exercise was 2-3 points on the Borg Conscious Ex-ercise Intensity Scale(i.e.,mild-to-moderate tachypnea or fatigue).The neck dissection injury index(NDII)was used to evaluate the quality of life related to shoulder joint function at four time points:preoperative,postoperative 3 months,postoperative 6 months,and postoperative 12 months.The higher the score,the better the quality of life.Results 28 cases in the test group and 32 cases in the control group completed a one-year follow-up.At 3 and 6 months postopera-tive,the NDII of the test group was significantly higher than that of the control group[3 months postoperative:test group(93.48±9.36)vs.control group(80.00±11.34)(P＜0.001),6 months postoperative:test group(98.21±4.76)vs.control group(90.70±9.12)(P＜0.001)];12 months after surgery,the NDII of the test group(97.23±4.88)was still higher than that of the control group(96.33±4.49),but the difference was not statistically significant(P=0.458).The difference in NDII scores among subjects at 3,6,and 12 months after surgery was statistically significant in each group(P＜0.001).Conclusion The application of the phased rehabilitation training method in neck dissection patients has a feasibility and could improve the quality of life of patients'shoulder joint function within 6 months after surgery.

BACKGROUND: Congenital heart disease (CHD) is one of the most common congenital malformations in humans. Inconsistent results emerged in the existed studies on associations between air pollution and congenital heart disease. The purpose of this study was to evaluate the association of gestational exposure to air pollutants with congenital heart disease, and to explore the critical exposure windows for congenital heart disease. METHODS: The nested case-control study collected birth records and the following health data in Tianjin Women and Children's Health Center, China. All of the cases of congenital heart disease from 2013 to 2015 were selected matching five healthy controls for each case. Inverse distance weighting was used to estimate individual exposure based on daily air pollution data. Furthermore, the conditional logistic regression with distributed lag non-linear model was performed to identify the association between gestational exposure to air pollution and congenital heart disease. RESULTS: A total of 8,748 mother-infant pairs were entered into the analysis, of which 1,458 infants suffered from congenital heart disease. For each 10 µg/m³ increase of gestational exposure to PM_2.5, the ORs (95% confidence interval, 95%CI) ranged from 1.008 (1.001-1.016) to 1.013 (1.001-1.024) during the 1^st-2^nd gestation weeks. Similar weak but increased risks of congenital heart disease were associated with O₃ exposure during the 1^st week and SO₂ exposure during 6^th-7^th weeks in the first trimester, while no significant findings for other air pollutants. CONCLUSIONS This study highlighted that gestational exposure to PM_2.5, O₃, and SO₂ had lag effects on congenital heart disease. Our results support potential benefits for pregnancy women to the mitigation of air pollution exposure in the early stage, especially when a critical exposure time window of air pollutants may precede heart development.
Infant ; Pregnancy ; Child ; Humans ; Female ; Air Pollutants/analysis* ; Case-Control Studies ; Prenatal Exposure Delayed Effects/epidemiology* ; Heart Defects, Congenital/etiology* ; China/epidemiology* ; Particulate Matter/adverse effects* ; Maternal Exposure/adverse effects*

Objective:To explore the therapeutic characteristics of population with gout achieving treat-to-target (T2T) indicators through real-world research and evaluate their safety.Methods:A total of 3 287 patients diagnosed with gout by rheumatologists in 21 first-class tertiary hospitals in 10 provinces, municipalities, and autonomous regions in China from January 2015 to December 2021 were included in this polycentric cross-sectional study. The database included patients′ general information, disease characteristics, and clinical application of traditional Chinese and Western medicine treatment measures. SPSS and Excel software were used for data analysis. Frequency analysis, cluster analysis, and factor analysis were used to summarize the characteristics and rules of treatment measures for patients with gout who achieved the target after treatment. The occurrence of adverse events (AE) was recorded during treatment.Results:After treatment, 691 visits (7%) achieved the serum urate (SUA) target, and the most frequent use of urate-lowering therapy (ULT) was febuxostat, followed by benzbromarone. The most common treatment options were following: GroupⅠ: traditional Chinese medicine (TCM) decoction-TCM external treatment-physical exercise-proprietary Chinese medicine; GroupⅡ: ferulic acid-nonsteroidal anti-inflammatory drugs (NSAIDs); Group Ⅲ: allopurinol-sodium bicarbonate-benzbromarone; Group Ⅳ: glucocorticoid-colchicine; Group Ⅴ: febuxostat. A total of 5 898 visits (60%) chieved manifestations of joint pain VAS scores target, and the most frequently used drug to control joint symptoms was NSAIDs. The frequency of use of drugs to control joint symptoms were 2 118 times (usage rate reached 35.9%), while the frequency of ULT were 2 504 times (usage rate reached 42.5%), which was higher than the joint symptom control drug. The most common treatment options were following: Group Ⅰ: proprietary Chinese medicine-TCM decoction-TCM external treatment-physical exercise; Group Ⅱ: NSAIDs-colchicine hormones; Group Ⅲ: allopurinol, Group Ⅳ: benzbromarone; Group Ⅴ: febuxostat. A total of 59 adverse events occurred during treatment.Conclusion:The proportions of gout patients who reach target serum urate level & good control of joint symptoms are both very low, and ULT and anti-inflammatory prescription patterns are very different from international guidelines, so it is necessary to strengthen the standardized management of gout patients. At the same time, life intervention measures account for a certain proportion of the treatment plans for the T2T population, and further exploration is needed.

Objective:To investigate the implementation status of sepsis hour-1 bundle strategy for patients with septic shock in emergency department.Methods:A total of 116 septic shock patients admitted to the emergency department from January 2020 to December 2020 were included in this prospective study, and the implementation of sepsis bundles and the clinical outcomes of patients were recorded.Results:Among 116 patients, 20 cases (17.2%) had lactic acid monitored within 1 h, 20 cases (17.2%) had blood culture before antibiotics, 82 cases (70.1%) received broad-spectrum antibiotics, 16 cases (13.8%) received fluid resuscitation ≥30 ml/kg, and 57 cases (49.1%) received vasoactive drugs during resuscitation. Finally, the sepsis hour-1 bundle strategy was fully implemented only in 13 cases (11.2%). Compared with the group with incomplete implementation of sepsis hour-1 bundle strategy, the volume of fluid recovery in the group with full implementation was significantly increased [33.7 (30.0,37.5) vs. 8.9(7.3,10.8) ml/kg, Z=-4.78, P<0.001], mean artery blood pressure significantly increased [70.0 (70.0,76.7) vs. 67.7 (61.7,76.7)mmHg(1 mmHg=0.133 kPa) , Z=-2.00, P<0.001], and lactic acid significantly decreased [3.0 (2.0,3.2) vs. 4.4 (3.7,7.2) mmol/L, Z=-2.76, P=0.006]. However, there were no significant differences in ICU mortality, in-hospital mortality and 28-day mortality between the two groups ( P>0.05). Conclusions:Septic shock patients in emergency department have poor compliance with the implementation of sepsis hour-1 bundle strategy, and relevant management training should be strengthened.

Objective:To investigate the apoptosis-inducing effect of baohuoside I (BI) on endometrial cancer Ishikawa cells and its related molecular mechanism.Methods:With 0 μ M and 0 h treatment were used as blank control group, and BI treatment was used as experimental group. The inhibitory effect of BI on the proliferation of Ishikawa cells was detected by CCK-8 assay. The apoptosis-inducing effect of BI on Ishikawa cells and the changes of mitochondrial membrane potential were detected by flow cytometry. The expressions of apoptosis-related proteins and signaling pathway-related proteins were detected by Western blot.Results:CCK-8 experiment showed that BI could be expressed in concentration gradient (3, 10, 20, 30, 40 μM). It could effectively inhibit the proliferation of Ishikawa cells (the survival rates were 89.56±0.96, 74.69±1.21, 60.28±1.09 and 43.51±2.17 respectively). Its toxic and side effects on normal cells were lower than that of 5-FU. The results of flow cytometry showed that BI could effectively induce the apoptosis of Ishikawa cells by reducing the level of mitochondrial membrane potential. The proportion of apoptotic cells in each group was (9.92±0.77) %, (14.01±0.83) %, (17.05±1.41) %, (28.21±1.73) % and (44.55±3.11) %. Western blot showed that BI could up-regulate the level of p-p38 and reduce the level of p-STAT3.Conclusions:BI can effectively inhibit the proliferation of Ishikawa cells, and induce apoptosis by reducing the mitochondrial membrane potential and activating the mitochondria-dependent pathway. Its regulatory mechanism is achieved by activating the p38 signaling pathway and inhibiting the STAT3 pathway.

Objective:To investigate the clinical characteristics and influencing factors of mortality in patients with intra-abdominal candidiasis (IAC).Methods:The retrospective case-control study was conducted. The clinicopathological data of 203 IAC patients who were admitted to 7 medical centers from June 2018 to June 2020 were collected, including 54 cases in Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, 31 cases in Fujian Medical University Union Hospital, 25 cases in Beijing Hospital, 25 cases in the First Affiliated Hospital of Xi'an Jiaotong University, 24 cases in China-Japan Friendship Hospital, 22 cases in General Hospital of Eastern Theater Command of Chinese PLA and 22 cases in Chongqing University Cancer Hospital. There were 130 males and 73 females, aged (64±15)years. Observation indicators: (1) candida infection and treatment of IAC patients; (2) analysis of influencing factors for mortality of IAC patients. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate and multivariate analyses were performed by Logistic regression model. Results:(1) Candida infection and treatment of IAC patients: 134 cases of candida albicans were cultured in the initial abdominal drainage fluid or intraoperative abdominal specimens of 203 patients, and 49 cases were treated with fluconazole. Of 69 cases infected with non candida albicans, 13 cases were treated with fluconazole. The resistance rate of candida albicans to fluconazole was 5.91%(12/203). Of 203 patients, there were 68 cases with infections shock, 53 cases with renal failure, 84 cases with respiratory failure and 63 cases with multiple organ failure, respectively. There were 148 of 203 patients admitted to intensive care unit for 9 days(range, 3-20 days), and the total hospital stay was 28 days(range, 17-50 days). Of 203 patients, 86 cases were cured and discharged, 50 cases were improved and transferred to local hospitals, 32 cases gave up treatment and discharged automatically, 19 cases died, 16 cases had no follow-up data. The mortality was 25.12%(51/203). (2) Analysis of influencing factors for mortality of IAC patients. Results of univariate analysis showed that acute physiology and chronic health evaluation score, sequential organ failure assessment score, the Cr, bilirubin, albumin, procalcitonin, and PLT on the first day of candida positive culture, of the lowest value in a week and the highest in a week, heart disease, diabetes, infections shock, renal failure, respiratory failure, multiple organ failure, anti-fungal therapy were the related factors for mortality of IAC patients ( t=-2.322, Z=-2.550, -2.262, -4.361, t=2.085, Z=-3.734, -5.226, -2.394, -5.542, t=3.462, Z=-4.957, -5.632, 3.670, -5.805, t=3.966, Z=-3.734, -5.727, χ2=4.071, 4.638, 27.353, 18.818, 13.199, 26.251, 13.388, P<0.05). Multivariate analysis showed that the bilirubin, procalcitonin on the first day of candida positive culture and infections shock were independent risk factors for mortality of IAC patients ( odds ratio=1.021, 1.022, 6.864, 95% confidence interval as 1.010-1.033, 1.001-1.044, 1.858-25.353, P<0.05). Conclusions:The common fungus of IAC was candida albicans, and fluconazole can be used as the initial empirical treatment. The prognosis of patients with abdominal candidiasis is poor. Bilirubin, procalcitonin on the first day of candida positive culture and infections shock are indepen-dent risk factors for mortality of IAC patients.

Objective:To evaluate the role of long-chain non-coding RNA-lung cancer metastasis-related transcript 1/microRNA-145/Bcl-2 and adenovirus E1B19k Da interacting protein 3 (Lnc-MALAT1/miRNA-145/BNIP3) signaling pathway in sufentanil preconditioning-induced cardioprotection in rats.Methods:Rat H9C2 cells were inoculated in 6-well culture plates or flasks at a density of 1×10 6 cells/ml and divided into 5 groups ( n=30 each) using a random number table method: control group (group C), hypoxia-reoxygenation (H/R) group, sufentanil preconditioning group (S group), eukaryotic expression vector pcDNA3.0 group (pcDNA group) and pcDNA-MALAT1 group (MALAT1 group). Cells were incubated with 10 μmol/L sufentanil for 2 h, and then the H/R injury model was established in group S. In pcDNA group and MALAT1 group, cells were transfected with pcDNA3.0 and pcDNA-MALAT1, respectively, and then incubated with 10 μmol/L sufentanil for 2 h starting from 24 h after transfection, and then the H/R injury model was established.At 2 h after reoxygenation, the expression of Lnc-MALAT1, miRNA-145 and BNIP3 mRNA was detected by real-time polymerase chain reaction, the cell survival rate was detected by CCK-8, the apoptosis rate was detected by flow cytometry, the malondialdehyde (MDA) and superoxide dismutase (SOD) levels and amount of lactic dehydrogenase (LDH) released were detected, and the expression of Bcl-2, Bax and cleaved-caspase-3 was detected by Western blot. Results:Compared with group C, the survival rate was significantly decreased, apoptosis rate was increased, the MDA level and amount of LDH released were increased, SOD levels were decreased, the expression of LncRNA-MALAT1, BNIP3 mRNA, Bax, and cleaved-caspase-3 was up-regulated, and miRNA-145 and Bcl-2 expression was down-regulated in the other four groups ( P<0.05). Compared with group H/R, the cell survival rate was significantly increased, apoptosis rate was decreased, the MDA level and amount of LDH released were decreased, SOD levels were increased, the expression of LncRNA-MALAT1, BNIP3 mRNA, Bax, and cleaved-caspase-3 was down-regulated, and miRNA-145 and Bcl-2 expression was up-regulated in S and pcDNA groups ( P<0.05). Compared with group S, the survival rate was significantly decreased, apoptosis rate was increased, MDA level and amount of LDH released were increased, SOD levels were decreased, the expression of LncRNA-MALAT1, BNIP3 mRNA, Bax, and cleaved-caspase-3 was up-regulated, and miRNA-145 and Bcl-2 expression was down-regulated in group MALAT1 ( P<0.05). Conclusion:The mechanism of sufentanil preconditioning-induced cardioprotection is related to inhibiting Lnc-MALAT1/miRNA-145/BNIP3 signaling pathway in rats.

During the Huai′an Emergency Alliance meeting in January 2020, 143 emergency physicians from 21 level Ⅱ general hospitals in the region who attended the meeting, participated in a questionnaire survey on the knowledge of hour-1 bundle therapy for septic shock. The average score of the correct answer was (5.4±2.9), that for senior ( n=39), intermediate ( n=50) and primary ( n=54) physicians was (6.4±3.3), (6.0±3.2) and (3.4±1.9), respectively ( P<0.01); the rate of failure (≤5) for them was 28% (11/39), 40% (20/50) and 56% (30/54) ( P=0.03), respectively. The hour-1 bundle was summarized into four measures. For the measure of "blood culture", 95% of all levels emergency physicians answered correctly. In answering question of "liquid resuscitation and vasoactive drugs" the accurate rate was 15% (6/39), 24% (12/50) and 7% (4/54) for senior, intermediate and primary physicians; while in answering questions about other measures the overall correct rates were all around 50%. The correct rate for "time of implementing the bundle" in intermediate, senior and primary physicians was 60% (30/60), 59% (23/39) and 44% (24/54); for "monitoring lactate timing" in intermediate, senior and primary physicians was 64% (32/50), 80% (31/39) and 65% (35/54); for the target value of "MAP" was 68% (34/50), 62% (24/39) and 50%(27/54); for the "use time of vascular active drug" was 50% (25/50), 46% (18/39) and 17% (9/54), respectively. The survey suggested that the knowledge of hour-1 bundle therapy for septic shock among emergency physicians in Huai′an secondary general hospitals are insufficient, and relevant training should be strengthened.

Objective:To explore the influences of different lying positions on vital signs and comforts in patients with tracheal intubation removed after intestinal fistula surgery.Methods:From October 2018 to June 2019, convenience sampling was used to select 150 patients with intestinal fistula surgery after general anesthesia in Intensive Care Unit of the General Hospital of Eastern Theater Command were selected as the research object. After waiting for the patient to wake up from anesthesia, the tracheal intubation was removed, and the lying position was changed after normal spontaneous breathing through the nose. Patients were randomly divided into 5 groups, 30 cases in each group. Group A was in the supine position; group B was in the lying position with the head of the bed raised by 15°; group C was in the lying position with the head of the bed raised by 30°; group D was in the lying position with the head of the bed raised by 45°; group E was in the lying position with the head of the bed raised by 15° to 45 °. At the beginning, the head of the bed was shaken to 15 °; and after two hours, the head of the bed was shaken to 30 °, and after another two hours, the head of the bed was shaken to 45 °. After 5 groups of patients fixed the angle of the lying position, when the patient complained of discomfort or the body position changed spontaneously, the patient changed the lying position. The duration of the lying position, uncomfortable symptoms and pain degree of abdominal incision were compared among 5 groups.Results:Patients with tracheal intubation removed after intestinal fistula surgery had a longer persistence in the 15° and 30° lying positions within 6 hours, respectively (72.27±12.41) min and (69.37±9.10) min. There were statistically significant differences in the persistence time of 5 different lying positions ( P<0.01) . The number of patients in group B and C with waist pain was less, and there were more patients with painless incisions, and there were statistically significant differences among 5 groups ( P<0.05) . Conclusions:Among patients with tracheal intubation removed and normal spontaneous breathing through the nose after intestinal fistula surgery, the 15° to 30° lying position within 6 hours after the operation can prolong the patient's adherence to the lying position, reduce the incidence of abdominal incision pain and waist pain, and reduce the probability of dizziness, nausea and vomiting.