Objective:To study the survival and prognostic factors for the recurrent extracranial malignant germ cell tumors (MGCTs) in children, and to explore feasible salvage treatment.Methods:A retrospective study.Pediatric patients with recurrent extracranial MGCTs diagnosed in Shanghai Children′s Medical Center between January 2010 and January 2020 were retrospectively recruited.Comprehensive treatment regimens included surgery, chemotherapy and radiation.Kaplan-Meier survival analysis and Cox regression model were employed to analyze the survival and prognostic factors for children with recurrent extracranial MGCTs.Results:A total of 172 children with extracranial MGCTs were treated, including 21 (12.2%) recurrent cases.The median time of MGCT recurrence after the end of the first treatment was 11 months.Finally, 19 patients were recruited after excluding 2 non-eligible cases, including 10 boys and 9 girls with the age at recurrence of 26 (8-170) months.The follow-up time was 57 (13-122) months.Salvage chemotherapy, complete resection and radiotherapy were performed in 16, 14 and 4 patients, respectively.The 4-year overall survival (4yr-OS) rate was (82.5±9.2)%(19 cases). The 4yr-OS rate was significantly higher in patients managed with surgery but without adjuvant chemotherapy at the initial treatment (13 cases) than those managed with chemotherapy at the initial treatment (6 cases)[(92.3±7.4)% vs.(60.0%±21.9)%, P=0.002]. Univariant and Cox multivariant regression analyses showed that failure to achieve the normal range of alpha fetoprotein after 3 cycles of chemotherapy significantly influenced the survival of recurrent extracranial MGCTs. Conclusions:For patients with recurrent extracranial MGCTs, comprehensive treatment approaches like complete surgical resection, chemotherapy, and radiotherapy offer a favorable survival rate.Specifically, recurrent and re-treated patients who initially received surgery alone without adjuvant chemotherapy have a higher survival rate compared to those who received chemotherapy during the initial treatment.

Objective To analyze the changes in fertility trends of seasonally and calendar adjusted fertility rate(SAFR)in different countries before and after the COVID-19 pandemic outbreak and investigate the influence factors.Methods Monthly SAFR data of 28 countries during January 2012 and December 2022 were collected in the Human Fertility Database(HFD).The node of December 2020(9-month delay in gestation from the start of the March 2020 outbreak)was used as the point of division for comparison between the pre-(2012.1-2020.11)and post-pandemic(2020.12-2022.12)periods.Interrupted time series was used to analyze whether fertility rate trends(short-term fluctuations and long-term trends)changed before and after the pandemic in each country.Wilcoxon test was employed to analyze whether pre-pandemic fertility rate,GDP per capita,public health and social measures(PHSM)and unemployment rate were associated with the changes in fertility trends.Results Nineteen out of the 28 countries experienced a short-term decline in fertility rate after the pandemic,which subsequently rebounded.With respect to long-term trends,2 countries shifted from a declining trend to an increasing trend,8 countries shifted from an increasing trend to a declining trend,and 6 countries had their SAFR unchanged.The SAFR decline was mainly observed in some of the countries of Central Europe and the Western Mediterranean,while its increase was mainly in Northern and Western Europe.Pre-pandemic SAFR was lower in the countries with no short-term fluctuations in SAFR than those with short-term fluctuations(P=0.041).The countries with declining rate of SAFR had significantly lower pre-pandemic SAFR(P=0.005)and GDP per capita(P=0.027)than the countries with increasing rate of SAFR.No association was found between short-term fluctuations or long-term trends in fertility rate and the PHSM severity index or unemployment rate.Conclusion The COVID-19 pandemic has had varying short-and long-term impacts on SAFR in 28 countries,with the countries with relatively low economic levels and pre-pandemic SAFRs more vulnerable to further blows.The longer-term impacts of the COVID-19 pandemic on the populations of each country deserve further attention.

Objective:To evaluate the association between N-acylsphingosine amide hydrolase 1 (ASAH1) and pyroptosis during acute lung injury (ALI) in septic mice.Methods:Forty SPF-grade healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-23 g, were divided into 4 groups ( n=10 each) by a random number table method: sham operation group (Sham group), ALI group, HCFU solvent+ ALI group (HA group) and ASAH1 inhibitor HCFU+ ALI group (AA group). The abdominal cavity was only opened in Sham group, and cecal ligation puncture was performed in ALI, HA and AA groups. HCFU solvent 0.2 ml was intraperitoneally injected at 2 h before operation in HA group, and HCFU 10 mg/kg was intraperitoneally injected at 2 h before operation in AA group. The mice were sacrificed at 24 h under deep anesthesia, the eyeballs were removed to collect the blood, the bronchoalveolar lavage fluid (BALF) was collected, and lung tissues and blood samples were collected for microscopic examination of the pathological changes (using HE staining) which were scored and for determination of concentrations of protein in BALF (by BCA method), concentrations of interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) in BALF (by enzyme-linked immunosorbent assay), and expression of NOD-like receptor thermoprotein structural domain-related protein 3 (NLRP3) in lung tissues (by Western blot), gasdermin D protein (GSDMD), ASAH1 and cysteine protease-1 (caspase-1) (by Western blot). The wet/dry lung weight (W/D) ratio was calculated. Results:Compared with Sham group, the lung injury score, W/D ratio and concentrations of protein in BALF, IL-1β, IL-6 and TNF-α in serum were significantly increased, and the expression of NLRP3, GSDMD and caspase-1 in lung tissues was up-regulated in ALI, HA and AA groups, and the expression of ASAH1 was significantly up-regulated in ALI and HA groups ( P<0.05). Compared with ALI and HA groups, the lung injury score, W/D ratio, and concentrations of protein in BALF, IL-1β, IL-6 and TNF-α in serum were significantly increased, the expression of NLRP3, GSDMD and caspase-1 in lung tissues was up-regulated, and the expression of ASAH1 was down-regulated in AA group ( P<0.05 or 0.01). Conclusions:ASAH1 is involved in the endogenous protective mechanism underlying ALI in septic mice, which may be related to the inhibition of cell pyroptosis.

Objective:To evaluate and screen the regimens of tigecycline intraventricular injection in extensively drug resistant Acinetobacter baumannii (XDRAB) intracranial infection based on Monte Carlo simulation and pharmacokinetic/pharmacodynamic (PK/PD) model.Methods:Nine patients with XDRAB intracranial infection confirmed as having susceptibility to tigecycline or polymyxin antimicrobials from January 1, 2018 to December 31, 2023 were screened from electronic medical record system in Second Affiliated Hospital of Shandong First Medical University. WHONET software was used to extract pathogen susceptibility data isolated from cerebrospinal fluid samples. Minimum inhibitory concentration (MIC) of tigecycline against XDRAB was analyzed by drug susceptibility test; different regimens for intraventricular tigecycline injection were designed based on MIC: 2 mg/12 h, 3 mg/12 h, 4 mg/12 h, 5 mg/12 h, 6 mg/12 h, and 10 mg/12 h, with drug concentration of 0.5 mg/mL or 1.0 mg/mL once a day. Target value of PK/PD index was set as ?C max/MIC≥8; Monte Carlo was used to simulate the compliance of PK/PD index of tigecycline with different MIC against XDRAB for different dosed regimens (probability of target attainment [PTA] and cumulative fraction of response [CFR]); the best regiment was selected (screening basis: PTA≥90% or CFR≥90%). Results:(1) A total of 27 strains of pathogenic bacteria from 9 patients were extracted from drug susceptibility test, in which MIC of tigecycline against XDRAB was 55.56% for 2 mg/L, 25.93% for 4 mg/L, and 18.52% for 8 mg/L. (2) When the drug concentration was 0.5 mg/mL or 1.0 mg/mL, respectively, all 6 regimens had PTA>90% at 2 mg/L MIC; 5 regimens, except for 2 mg/12 h, had PTA>90% at 4 mg/L MIC; regimens of 5 mg/12 h, 6 mg/12 h, and 10 mg/12 h could achieve PTA>90% at 8 mg/L MIC. (3) When the drug concentration was 0.5 mg/mL, regimens of 4 mg/12 h, 5 mg/12 h, 6 mg/12 h, and 10 mg/12 h could achieve CFR>90%; when the drug concentration was 1 mg/mL, regimens of 4 mg/12 h, 5 mg/12 h, 6 mg/12 h, and 10 mg/12 h could achieve CFR>92%.Conclusion:In intraventricular tigecycline injection for XDRAB intracranial infection, 2 mg/12 h regimen is available in 2 mg/L MIC, 3 mg/12 h regimen is available in 4 mg/L MIC, and 5 mg/12 h regimen is available in 8 mg/L MIC, with either 0.5 mg/mL or 1 mg/mL concentration.

Objective:To explore application of mixed teaching platform in the clinical practice teaching of the laboratory medicine in Children's hospitals.Methods:We constructed a mixed online and offline teaching platform based on the Laboratory Quality Management System (LQMS) in the Children's Hospital of Chongqing Medical University. The undergraduates from Batch 2016 ( n=15) and Batch 2018 ( n=12) of College of Laboratory Medicine of Chongqing Medical University were taken as control group and experimental group respectively. Traditional teaching method was adopted by the control group, and the mixed teaching method was adopted by the experimental group. The results of two groups' clinical practice assessment, rate of outstanding students (total score ≥ 90) and rate of satisfaction (score ≥ 90) were compared to evaluate the teaching effect. SPSS 17.0 was used to conduct t-test and Chi-square test. Results:The database of teaching platform includes 68 teaching cases, 198 pieces of courseware, 305 clinical cases and 3 036 atlases. The test bank has accumulated 4 657 tests, covering clinical laboratory, immunology, biochemistry, microbiology and blood transfusion. The results of students in experimental group were significantly better than those of the control group [the score of clinical practice assessment: (85.90±5.04) vs. (78.90±6.75)( P<0.05); rate of outstanding students: 33.3% (4/12) vs. 6.7% (1/15), P>0.05; rate of satisfaction: 86.7% (13/15) vs. 100.0% (12/12) ( P>0.05). Conclusion:The mixed online and offline teaching platform based on the LQMS is highly recognized by students and can significantly improve the effect of clinical practice teaching, which can provide typical medical case teaching at any time and make up for limited case type in children's hospital.

Objective:To determine the therapeutic effect of in vitro cultivation of bezoar on a mouse model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. Method:BALB/c mice were randomly divided into six groups according to their weight grade： normal group， HCoV-229E infection group， cold and damp group， a mouse model combining disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome， and high and low dose group of in vitro cultivation of bezoar. The combination model of human coronavirus pneumonia with Yidu Xifei syndrome mice was established by the method of cold dampness condition stimulation+coronavirus HCoV-229E infection. In vitro cultivation of bezoar （0.128，0.064 g·kg^-1） was administrated by gavage for 3 days from the day of infection. The observation indexes included： general state observation of mice， inhibition rate of lung index and lung index of mice. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the viral load in the lung tissues of mice. Serum levels of motilin（MTL）， gastrin （GAS）， and cytokines interleukin（IL）-10，IL-6， tumor necrosis factor-α（TNF-α）and interferon-γ（IFN-γ） in lung tissue of mice were determined by enzyme-linked immunosorbent assay（ELISA）. The percentages of CD4⁺ T lymphocytes，CD8⁺ T lymphocytes and B lymphocytes in the blood of mice were determined by flow cytometry. Result:The high and low dose group of in vitro cultivation of bezoar can significantly improve the general condition of model mice. Compared with blank group， model group mice lung index increased significantly （P<0.01）， nucleic acids significantly increased expression of lung tissue in mice （P<0.01）， significantly higher serum MTL content in mice， GAS content significantly decreased （P<0.05，P<0.01）， lung tissue cells in the immune factor TNF-α， IL-10 and IL-6 were significantly increased （P<0.01）， peripheral blood lymphocyte CD4⁺ T cells in mice， The percentages of CD8⁺ T cells and B cells were significantly decreased （P<0.01）. Compared with model group， in vitro cultivation bezoar mice lung index of high and low dose group were significantly lower （P<0.01）， the lung tissue of mice express nucleic acid decreased significantly （P<0.01）， MTL content decreased significantly （P<0.01）， the lung tissue of mice in the IL-6， IL-10， the TNF-α， IFN-γ levels were significantly lower （P<0.01）， in vitro cultivation bezoar high dose group can significantly increase the CD4⁺ T cell percentage （P<0.05）， in vitro cultivation bezoar can to a certain extent reduce model mice lung inflammatory exudation， pulmonary interstitial edema， as well as blood stasis symptoms. Conclusion:In vitro cultivation of bezoar has a significant therapeutic effect on a mice model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. It can be treated by reducing the lung index of the model mice， improving the pathological damage of the lung tissue， adjusting the immune effective and inhibiting the clearing of inflammatory factors， and to provide a laboratory basis for clinical medication.

Objective:To investigate the differential expression of miRNAs during white adipose tissue(WAT)browning in mice under different stimulation conditions, and to analyze the potential regulatory mechanisms.Methods:Mouse models of subcutaneous WAT(sWAT)browning were established by different methods: cold-induced browning and intraperitoneal injection of CL316-243.HE staining and analysis of thermogenesis-related gene expression were used to validate the browning models.miRNAs expression profiles in different conditions were described by RNA-sequencing(RNA-seq)and miRNAs with similar expression patterns in the two groups were detected via screening.Target genes of miRNAs were predicted by bioinformatics, and their expression levels were verified by quantitative real-time PCR(qRT-PCR).Results:Both cold-induced browning and intraperitoneal injection of CL316-243 were able to activate the browning of sWAT, and the miRNA expression profile of sWAT showed significant differences before and after induction.After screening differentially expressed miRNAs, the expression of Mir-30E-3p was increased and the expression of Mir-181A-5p was decreased under different browning-inducing conditions in WAT.The prediction and validation of target genes revealed that cyclin-dependent kinase 6(Cdk6)and sirtuin 1(Sirt1)were potential targets regulated by miR-30e-3p and miR-181a-5p in the browning of sWAT, respectively.Conclusions:There are significant differences in miRNA expression during the browning of sWAT in mice induced by cold stimulation and CL316-243 injection.MiR-30e-3p and miR-181a-5p may be involved in the regulation of the sWAT browning process through target genes Cdk6 and Sirt1, respectively.

Objective To study the short-term and medium-term effects of mini- strip anchor and capsulotomy in the treatment of first metacarpophalangeal joint dislocation in rheumatoid arthritis (RA). Methods From January 2015 to December 2016,fifty-eight RA patients with first metacarpophalangeal joint dislocation were randomly divided into study group (20 cases),joint replacement group (19 cases) and non-operation group (19 cases). Postoperative evaluation indexes: the wound healing was observed in accordance with ＂trial standard of functional evaluation of upper limbs of Chinese Medical Association Hand Surgery Society＂. The surgical outcomes of the three groups were compared. The hand function and quality of life were assessed by Michiga Hand Outcomes Questionnaire ( MHQ ) and arthritis impact measurement scale 2 (AIMS2) before treatment, 6 months after treatment and 12 months after treatment. Results All the patients in the study group and the joint replacement group healed by first intention without any early complications. According to the criteria of upper extremity functional evaluation of Chinese Medical Association,the curative effect of the operation was evaluated. In the study group,15 cases were excellent,3 cases were good,2 cases were poor,the excellent and good rate was 90. 0%. In the joint replacement group, 15 cases were excellent,3 cases were good,1 case was poor,and the excellent and good rate was 94. 7%. After treatment for 6months, the MHQ scores were improved significantly in the three groups (( 48. 36 ±8. 24) vs. (73. 06±10. 55); (47. 56±7. 75) vs. (81. 42±8. 54); (48. 75±8. 85) vs. (65. 91±8. 26)) (F＝33. 19,35. 12,28. 42, P＜0. 05). The MHQ scores of study group ( (73. 06±10. 55)points) and joint replacement group ( ( 81. 42 ± 8. 54) points) were significantly higher than those of non-operation group ((65. 91± 8. 26) points) ( P＜0. 05), and the MHQ scores of joint replacement group were significantly higher than those of study group (P＜0. 05). At 12 months after treatment,there was no significant difference in MHQ score between the study group ((82. 45±7. 18)points) and the arthroplasty group ((84. 36±6. 33) points) (P＞0. 05) . At 6 and 12 months after treatment, AIMS2 scores of each group were significantly improved,but AIMS2 scores of study group (( 216. 51 ± 35. 28) points, ( 230. 28 ± 23. 51) points) and arthroplasty group ((221. 45±31. 63) points,(234. 15±21. 42) points) were significantly higher than those of non-operation group ((192.69±41.31) points,(200.43 ±28.42) points) (P＜0.05).At 6 and 12 months after treatment,there was no significant difference in AIMS2 scores between the study group and the arthroplasty group ( P ＞ 0. 05 ) . Conclusion Micro-strip line anchors combined with posterior capsulorrhaphy in the treatment of first metacarpophalangeal joint dislocation in rheumatoid arthritis can achieve good stability of articular reduction,significantly improve the joint function and quality of life and have ideal short-term and mid-term effect.

Objective To investigate the clinical utility of magnifying endoscopy combined with nar-row-band imaging( ME-NBI)and endoscopic ultrasonography( EUS)in predicting the depth of early eso-phageal cancer. Methods Sixty-eight patients with early esophageal cancer after gastroscopic and pathological diagnosis were enrolled in Jiangsu Provincal Hospital of Traditional Chinese Medicine from January 2017 to May 2018,ME-NBI and EUS were performed preoperatively to determine the depth of lesion infiltration respectively, the accuracies of the two methods were calculated by referring to the postoperative pathology,and the McNemar test and Kappa test were used for comparison. Results The lesion confined to shallow mucosa and submucosa superficial layer was confirmed in 57 patients by postoperative pathology,submucosa superficial below in 11 pa-tients. Compared with that of histology,the ability of assessment of the invasion depth was moderately consistent with ME-NBI(McNemar test P = 0. 508;Kappa = 0. 560,P < 0. 001),not with EUS(McNemar test P =0. 019;Kappa = 0. 266,P = 0. 015). The accuracy for assessing invasion depth of early esophageal cancer was 86. 8％(59 / 68)by ME-NBI,72. 1％(49 / 68)by EUS,respectively,with statistically significant difference (McNemar test P = 0. 015;Kappa = 0. 258,P = 0. 026). Conclusion ME-NBI and EUS can help to deter-mine the infiltration level of early esophageal cancer. The accuracy of ME-NBI is higher,which is of high value for the formulation of surgical plans for patients.

Objective To compare the safely between 3 ways of inserting the anteroinferior iliac spine channel screws using computer simulation.Methods The spiral pelvic CT data of 100 patients were collected who had sought medical treatment at General Hospital of The Northern Theater Command from October 2017 to October 2018.They were 61 males and 39 females,aged from 20 to 60 years (average,47.5 years).The data were imported into Mimics (Materi-alise,Belgium) software to create three-dimensional models of the pelvis.The pelvic modeling data were then imported into 3-Matic (Materi-alise,Belgium) software for post-processing.Three cylinders with a diameter of 6.7 mm were created,taking the anteroinferior iliac spine as the entry point and taking the posterosuperior iliac spine,the posteroinferior iliac spine and the midpoint between the 2 spines as the 3 exit points.The insertion of anteroinferior iliac spine channel screws was simulated to observe the screw penetration.Results In the channel from the anteroinferior iliac spine to the posterosuperior iliac spine,penetration occurred in 41 cases out of the medial ilium and in 2 cases out of the lateral ilium,giving a penetration rate of 43％ (43/100);in the channel from the anteroinferior iliac spine to the midpoint between the 2 spines,penetration occurred in 16 cases out of the medial ilium and in 2 cases out of the lateral ilium,giving a penetration rate of 18％ (18/100);in the channel from the anteroinferior iliac spine to the posteroinferior iliac spine,penetration occurred in 6 cases out of the medial ilium,in 2 cases out of the lateral ilium,in 60 cases out of the greater sciatic notch and in 8 cases out of both the medial ilium and greater sciatic notch,giving a penetration rate of 76％ (76/100).There were significant differences between the 3 ways of insertion in the screw penetration (x2 =68.219,P ＜ 0.001).The rate of screw penetration in the channel from the anteroinferior iliac spine to the posteroinferior iliac spine was significantly higher than that in the channel from the anteroinferior iliac spine to the posterosuperior iliac spine which was significantly higher than that in the channel from the anteroinferior iliac spine to the midpoint between the 2 spines (P ＜ 0.05).Conclusions The channel from the anteroinferior iliac spine to the midpoint between the posterosuperior iliac spine and the posteroinferior iliac spine may lead to a lower rate of screw penetration while the channel from the anteroinferior iliac spine to the posteroinferior iliac spine may lead to a higher rate of screw penetration.