Umbilical cord blood cell characteristics in very preterm neonates for autologous cell therapy of preterm-associated complications.

BACKGROUND: There are emerging clinical evidence for umbilical cord blood mononuclear cells (UCBMNCs) intervention to improve preterm complications. The first critical step in cell therapy is to obtain high-quality cells. This retrospective study aimed to investigate the quantity and quality of UCBMNCs from very preterm infants (VPIs) for the purpose of autologous cell therapy in prevention and treatment of preterm complications. METHODS: Very preterm infants (VPIs) born in Guangdong Women and Children Hospital from January 1, 2017, to December 8, 2022, from whom cord blood was successfully collected and separated for public or private banking, were enrolled. The UCBMNCs characters from route cord blood tests performed in cord blood bank, impact of perinatal factors on UCBMNCs, the relationship between UCBMNCs characteristics and preterm outcomes, and the correlation of UCBMNCs characteristics and peripheral blood cells in VPIs were analyzed. RESULTS: Totally, 89 VPIs underwent UCB collection and processing successfully. The median cell number post processing was 2.6 × 108. To infuse a dose of 5 × 107 cells/kg, only 3.4% of infants required a volume of more than 20 mL/kg, which exceeded the maximum safe volume limit for VPIs. However, when infusing 10 × 107 cells/kg, 25.8% of infants required a volume of more than 20 ml/kg volume. Antenatal glucocorticoids use and preeclampsia was associated with lower original UCBMNCs concentration. Both CD34+ hematopoietic stem cells (HSC) frequency and colony forming unit - granulocyte and macrophage (CFU-GM) number correlated negatively with gestational age (GA). UCBMNCs characters had no significant effect on preterm outcomes, whereas a significant positive correlation was observed between UCBMNCs concentration and total white blood cell, neutrophil, lymphocyte and PLT counts in peripheral blood. CONCLUSION: UCBMNCs collected from VPIs was feasible for autologous cell therapy in improving preterm complications. Setting the infusion dose of 5 × 107 cells/kg guaranteed a safe infusion volume in more than 95% of the targeted infants. UCBMNCs characters did not affect preterm complications; however, the effect of UCBMNCs concentration on peripheral blood classification count should be considered when evaluating the immunomodulation of UCBMNCs transfusion.

Prevention for moderate or severe BPD with intravenous infusion of autologous cord blood mononuclear cells in very preterm infants-a prospective non-randomized placebo-controlled trial and two-year follow up outcomes.

Background: Bronchopulmonary dysplasia (BPD) is the primary severe complication of preterm birth. Severe BPD was associated with higher risks of mortality, more postnatal growth failure, long term respiratory and neurological developmental retardation. Inflammation plays a central role in alveolar simplification and dysregulated vascularization of BPD. There is no effective treatment to improve BPD severity in clinical practice. Our previous clinical study showed autologous cord blood mononuclear cells (ACBMNCs) infusion could reduce the respiratory support duration safely and potential improved BPD severity. Abundant preclinical studies have reported the immunomodulation effect as an important mechanism underlying the beneficial results of stem cell therapies in preventing and treating BPD. However, clinical studies assessing the immunomodulatory effect after stem cells therapy were rare. This study was to investigate the effect of ACBMNCs infusion soon after birth on prevention for severe BPD and long term outcomes in very preterm neonates. The immune cells and inflammatory biomarkers were detected to investigate the underlying immunomodulatory mechanisms. Methods: This single-center, prospective, investigator-initiated, non-randomized trial with blinded outcome assessment aimed to assess the effect of a single intravenous infusion of ACBMNCs in preventing severe BPD (moderate or severe BPD at 36 weeks of gestational age or discharge home) in surviving very preterm neonates less than 32 gestational weeks. Patients admitted to the Neonatal Intensive Care Unit (NICU) of Guangdong Women and Children Hospital from July 01, 2018 to January 1, 2020 were assigned to receiving a targeted dosage of 5 × 107 cells/kg ACBMNC or normal saline intravenously within 24 h after enrollment. Incidence of moderate or severe BPD in survivors were investigated as the primary short term outcome. Growth, respiratory and neurological development were assessed as long term outcomes at corrected age of 18-24 month-old. Immune cells and inflammatory biomarkers were detected for potential mechanism investigation. The trial was registered at ClinicalTrials.gov (NCT02999373). Findings: Six-two infants were enrolled, of which 29 were enrolled to intervention group, 33 to control group. Moderate or severe BPD in survivors significantly decreased in intervention group (adjusted p = 0.021). The number of patients needed to treat to gain one moderate or severe BPD-free survival was 5 (95% confidence interval: 3-20). Survivors in the intervention group had a significantly higher chance to be extubated than infants in the control group (adjusted p = 0.018). There was no statistical significant difference in total BPD incidence (adjusted p = 0.106) or mortality (p = 1.000). Incidence of developmental delay reduced in intervention group in long term follow-up (adjusted p = 0.047). Specific immune cells including proportion of T cells (p = 0.04) and CD4+ T cells in lymphocytes (p = 0.03), and CD4+ CD25+ forkhead box protein 3 (FoxP3)+ regulatory T cells in CD4+ T cells increased significantly after ACBMNCs intervention (p ï¼œ 0.001). Anti-inflammatory factor IL-10 was higher (p = 0.03), while pro-inflammatory factor such as TNF-a (p = 0.03) and C reactive protein (p ï¼œ 0.001) level was lower in intervention group than in control group after intervention. Interpretation: ACBMNCs could prevent moderate or severe BPD in surviving very premature neonates and might improve neurodevelopmental outcomes in long term. An immunomodulatory effect of MNCs contributed to the improvement of BPD severity. Funding: This work was supported by National Key R&D Program of China (2021YFC2701700), National Natural Science Foundation of China (82101817, 82171714, 8187060625), Guangzhou science and technology program (202102080104).

Research progress of tRNA-derived fragments as biomarkers for diagnostic and prognostic assessment of tumors / 国际生物医学工程杂志

Cancer is the second-leading cause of death worldwide. Cancer mortality is largely caused by the absence of recognizable early signs and a poor prognosis. Therefore, developing efficient diagnostic and prognostic biomarkers is crucial to reducing the incidence of cancer and improving its prognostic accuracy. tRNA-derived fragments are a new class of non-coding RNAs with important regulatory roles in cancer biology. In this paper, the research progress of tRNA-derived fragments as biomarkers in tumorigenesis, development, and prognosis was reviewed to provide a theoretical basis for cancer diagnosis and prognostic assessment.

Spatial transcriptome analysis of long non-coding RNAs reveals tissue specificity and functional roles in cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Long non-coding RNAs (lncRNAs) play a significant role in maintaining tissue morphology and functions, and their precise regulatory effectiveness is closely related to expression patterns. However, the spatial expression patterns of lncRNAs in humans are poorly characterized. Here, we constructed five comprehensive transcriptomic atlases of human lncRNAs covering thousands of major tissue samples in normal and disease states. The lncRNA transcriptomes exhibited high consistency within the same tissues across resources, and even higher complexity in specialized tissues. Tissue-elevated (TE) lncRNAs were identified in each resource and robust TE lncRNAs were refined by integrative analysis. We detected 1 to 4684 robust TE lncRNAs across tissues; the highest number was in testis tissue, followed by brain tissue. Functional analyses of TE lncRNAs indicated important roles in corresponding tissue-related pathways. Moreover, we found that the expression features of robust TE lncRNAs made them be effective biomarkers to distinguish tissues; TE lncRNAs also tended to be associated with cancer, and exhibited differential expression or were correlated with patient survival. In summary, spatial classification of lncRNAs is the starting point for elucidating the function of lncRNAs in both maintenance of tissue morphology and progress of tissue-constricted diseases.

Efficacy of wrist arthroscopic transosseous footprint repair technique for the treatment of triangular fibrocartilage complex injury / 中华创伤杂志

Objective:To investigate the clinical efficacy of wrist arthroscopic transosseous footprint repair technique for treating triangular fibrocartilage complex (TFCC) injury.Methods:A retrospective case series study was conducted to analyze the clinical data of 56 patients with TFCC injury admitted to Shenzhen Second People′s Hospital from July 2017 to September 2020, including 38 males and 18 females, aged 17-45 years [(33.5±3.6)years]. All patients had unilateral injury. Physical examination showed instability of the distal radioulnar joint, and MRI and arthroscopy confirmed deep ligament injury of TFCC. All patients underwent repair of deep insertion of the TFCC by using wrist arthroscopic transosseous footprint. The operation time, intraoperative blood loss, wound healing and postoperative complications were recorded. The flexion and extension range of motion of the wrist, radial and ulnal deviation of the wrist, rotation range of motion of the forearm, patient related wrist evaluation (PRWE) score, modified Mayo wrist score, visual analogue scale (VAS), and percentage of grip strength between the affected side and unaffected side were compared preoperatively, at 3 months postoperatively and at 1 year postoperatively.Results:All patients were followed up for 12-18 months [(13.4±5.2)months]. The operation time was (61.3±8.9)minutes, with the intraoperative blood loss of (2.4±1.2)ml. All wounds were healed by first intension. There was no wound infection or ulnar nerve irritation symptom after operation. Four patients experienced clicking on the ulnar side of the wrist in a short period of time post-operation, with spontaneous disappearance of the symptom. At 3 months postoperatively, the radial and ulnar deviation of the wrist was decreased from (52.5±5.9)° preoperatively to (42.6±5.9)°, and rotation range of motion of the forearm was decreased from (94.9±8.4)°preoperatively to (84.6±5.9)° (all P<0.01). The flexion and extension range of motion of the wrist was (93.1±17.4)° preoperatively, with insignificant difference compared with (89.4±5.8)° at 3 months postoperatively ( P>0.05). At 1 year postoperatively, the flexion and extension range of motion of the wrist, radial and ulnar deviation range of motion of the wrist, and rotation range of motion of the forearm were significantly increased to (101.3±13.6)°, (52.4±6.6)°, and (116.4±16.4)° when compared with those at 3 months postoperatively (all P<0.01). At 3 months postoperatively, the PRWE score was increased to (17.1±3.8)points from (10.6±3.2)points preoperatively ( P<0.01), modified Mayo wrist score was decreased to (70.3±6.7) points from (78.1±12.7)points preoperatively ( P<0.01), VAS was decreased to (4.4±1.7)points from (6.2±1.5)points preoperatively ( P>0.05), and percentage of grip strength between the affected side and unaffected side was decreased to (55.7±8.7)% from (74.4±15.2)% preoperatively ( P<0.01). At 1 year postoperatively, the PRWE score was increased to (2.0±0.9)points, modified Mayo wrist score was increased to (94.8±3.3)points, VAS was decreased to (2.1±1.1)points, and percentage of grip strength between the affected side and unaffected side was increased to (93.2±8.7)% when compared with those at 3 months postoperatively (all P<0.01). Conclusion:Wrist arthroscopic transosseous footprint repair technique can effectively treat deep ligament injury of TFCC, with advantages of significantly improving postoperative joint range of motion and functional score, relieving the pain on the ulnar side of the wrist and enhancing grip strength.

Epidemiological characteristics, diagnosis, treatment and prognosis of gallbladder cancer in China: a report of 6 159 cases / 中华消化外科杂志

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

Visual analysis of critical care research based on Web of Science core set / 中国实用护理杂志

Objective:To analyze the data of critical care related literatures published in Web of Science core set by knowledge map visualizing technology, and summarize the research status and hotspots of critical care.Methods:The core set database of Web of Science from January 2011 to December 2020 was searched, the extracted information was standardized and analyzed by knowledge map visualizing technology.Results:A total of 783 articles in the field of critical care were included, and the number of literatures increased year by year, among which the number of articles published in the American Journal of Critical Care(305) was the most. The United States (437) was the country with the most published literatures, and Australia was the country with the highest centrality (centrality=0.67). The number and centrality of articles published from China were at the lower middle level. There was cooperation among countries, but not close cooperation. The cooperation among authors was in the state of small aggregation and large dispersion. Cluster analysis and keyword emergence analysis showed that many aspects in the field of intensive care had been the research hotspots, among which "post intensive care syndrome" and "children′s intensive care" were the research hotspots in recent years.Conclusions:The research field of intensive care is still in the rising stage of development, and post intensive care syndrome and children's intensive care are the latest hotspots in intensive care research.

Research progress of the impact of payment by disease diagnosis-related group on nursing care / 中国实用护理杂志

The National Medical Insurance Administration launched a national pilot project based on diagnosis-related group (DRG) payment across the country in 2019. It optimizes and reuses limited resources from a clinical perspective, controls hospitalization expenses and medical costs, and reduces average hospital stays based on DRG payment. This article expounds the concept and application of DRG payment, from the perspective of clinical nursing, expounds the research progress of DRG payment at home and abroad, attempts to analyze the relationship between DRG payment and nursing, and further proposes the impact on the development of clinical nursing.

Application progress of liquid biopsy in the diagnosis and treatment of biliary tract cancer / 中华肝胆外科杂志

With the development of precision medicine and individualized treatment, tissue biopsy in cancer patients diagnosis and therapy has been broadly used. However, because it’s hard to collect enough samples for biliary tract tumors, liquid biopsy was broadly applied for the diagnosis. In liquid biopsy, circulating tumor cells, circulating tumor DNA, and tumor-derived exosomes carrying tumor-specific information are released from tumor tissue into blood, bile, and other body fluids, which makes tumor biopsy samples easily to be obtained in a non-invasive way. At the same time, through a series of morphological and molecular measurements as well as genetic characterization, liquid biopsy can be used to look for the new early diagnostic markers, and therapeutic targets, monitoring progression and prognosis of diseases. This article outlined the current technology used to detect circulating tumor cells, circulating tumor DNA, and tumor-derived exosomes, and summarizes the latest advances in the clinical application of liquid biopsy in biliary tract cancers.

The Trans-omics Landscape of COVID-19

System-wide molecular characteristics of COVID-19, especially in those patients without comorbidities, have not been fully investigated. We compared extensive molecular profiles of blood samples from 231 COVID-19 patients, ranging from asymptomatic to critically ill, importantly excluding those with any comorbidities. Amongst the major findings, asymptomatic patients were characterized by highly activated anti-virus interferon, T/natural killer (NK) cell activation, and transcriptional upregulation of inflammatory cytokine mRNAs. However, given very abundant RNA binding proteins (RBPs), these cytokine mRNAs could be effectively destabilized hence preserving normal cytokine levels. In contrast, in critically ill patients, cytokine storm due to RBPs inhibition and tryptophan metabolites accumulation contributed to T/NK cell dysfunction. A machine-learning model was constructed which accurately stratified the COVID-19 severities based on their multi-omics features. Overall, our analysis provides insights into COVID-19 pathogenesis and identifies targets for intervening in treatment.

Adjuvant corticosteroid therapy for critically ill patients with COVID-19

Addition of adjuvant corticosteroid therapy to standard antiviral treatment of patients with coronavirus disease (COVID-19) is common in clinical practice. However, evidence is scarce regarding the efficacy of adjuvant corticosteroids in patients who are critically ill. We retrospectively evaluated the effects of adjuvant corticosteroid treatment on the outcome of 244 critically ill patients with COVID-19, using a risk stratification model that adjusts for potential differences between the steroid group (n=151) and the non-steroid group (n=93). We observed that adjuvant corticosteroid therapy was independent from 28-day mortality, either in multivariate logistic regression of the entire cohort after adjustment for major mortality-associated variables (age, SpO2/FiO2, and lymphocyte count) and individual propensity score (adjusted OR: 1.05; 95% CI: -1.92-2.01), or in propensity score-matched (1:1 without replacement) case-control analysis (62 patients in 31 pairs; log-rank test P=0.17). Additionally, subgroup analyses of 147 (60%) patients who had dyspnea and 87 (36%) patients who had ARDS revealed corticosteroid treatment was not associated with clinical outcome (both, P>0.3). However, increased corticosteroids dosage was significantly associated with elevated mortality risk after adjustment for administration duration (P=0.003); every ten-milligram increase in hydrocortisone-equivalent dosage was associated with additional 4% mortality risk (adjusted HR: 1.04, 95% CI: 1.01-1.07). Our findings indicated that limited effect of corticosteroid therapy could pose to overall survival and prudent dose within effective limits may be recommended for critically ill patients under certain circumstances.

Classification of COVID-19 in intensive care patients: towards rational and effective clinical triage

The number of pertinent researches of COVID-19 has increased rapidly but they mainly focused on the description of general information of patients with confirmed infection. We aimed to bridge the gap between disease classification and clinical outcome in intensive care patients, data of which are scarce and such classification could help in individual evaluation and provide effective triage for treatment and management. Specifically, we collected and filtered out 151 intensive care patients with complete medical records from Tongji hospital in Wuhan, China. We constructed a fully Bayesian latent variable model for integrative clustering of six data categories, including demographic information, symptoms, original comorbidities, vital signs, blood routine tests and inflammatory marker measurements. We identified four prognostic types of COVID-19 in intensive care patients, presenting a stepwise distribution in age, respiratory condition and inflammatory markers, suggesting the prognostic efficacy of these indicators. This report, to our knowledge, is the first attempt of dealing with classification of COVID-19 in intensive care patients. We acknowledge the limitation of ignoring the effect of treatment, but we believe such classification is enlightening for better triage, allowing for a more rational allocation of scarce medical resources in a resource constrained environment.

Validation of reported risk factors for disease classification and prognosis in COVID-19: a descriptive and retrospective study

Risk indicators viral load (ORF1ab Ct), lymphocyte percentage (LYM%), C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT) and lactic acid (LA) in COVID-19 patients have been proposed in recent studies. However, the predictive effects of those indicators on disease classification and prognosis remains largely unknown. We dynamically measured those reported indicators in 132 cases of COVID-19 patients including the moderate-cured (moderated and cured), severe-cured (severe and cured) and critically ill (died). Our data showed that CRP, PCT, IL-6, LYM%, lactic acid and viral load could predict prognosis and guide classification of COVID-19 patients in different degrees. CRP, IL-6 and LYM% were more effective than other three factors in predicting prognosis. For disease classification, CRP and LYM% were sensitive in identifying the types between critically ill and severe (or moderate). Notably, among the investigated factors, LYM% was the only one that could distinguish between the severe and moderate types. Collectively, we concluded that LYM% was the most sensitive and reliable predictor for disease typing and prognosis. During the COVID-19 pandemic, the precise classification and prognosis prediction are critical for saving the insufficient medical resources, stratified treatment and improving the survival rate of critically ill patients. We recommend that LYM% be used independently or in combination with other indicators in the management of COVID-19.

Arthroscopic bone grafting with percutaneous fixation in treating scaphoid nonunion / 中华骨科杂志

Objective To analyze the clinical effects of arthroscopic autologous bone grafting and percutaneous fixation in treating scaphoid nonunion.Methods From May 2013 to August 2017,a total of 25 cases of patients including 20 males and 5 females with unilateral scaphoid fractures and nonunion were reviewed,with mean age of 35.80±2.41 years (18-65 years).The duration from injury to treatment was averaged 11.70± 1.90 months (5-18 months).All of the cases sustained waist and proximal end fractures.X-ray and CT scan showed sclerosis and bone resorption without any callus at the fracture sites.However,there were no serious deformities and wrist arthritis.The patients suffered pain and weakness at the radial side of the wrist.The type of the fractures were Slade-Geissler's Ⅲ-Ⅵ,including grade Ⅲ 4 cases,grade Ⅳ 13 cases,grade Ⅴ 7 cases and grade Ⅵ 1 case.The patients were treated with arthroscopic debridement of the sclerotic bone,autologous bone grafting,percutaneous screw (9 cases) or K-wires fixation (16 cases) and immobilization by plaster for 3 weeks after operation,followed by functional rehabilitation training.Bone union was assessed by serial plain radiographs and CT scan regularly.The functional effects were evaluated by comparing the modified Mayo wrist score with the visual analogue scale (VAS) for pain,range of motion (ROM) and the grip strength,which were measured before operation and at 18 months after operation.Results All cases were followed up.Bone union was achieved in all of 25 nonunion.The average radiological union duration was 10.24±2.10 weeks (6-20 weeks).The average VAS score decreased from 6.75± 1.10 preoperatively to 1.33±0.21.The mean ROM of wrist was improved to 168.48°± 12.41 ° (92.90％ of that of the normal side),compared to that of 135.24°± 17.47° preoperatively (79.80％ of that of the normal side).The mean grip strength showed improvement from an average of 35.68±3.81 kg (80.46％ of that of normal side) preoperatively to 48.75±4.42 kg (90.65％ of that of normal side).The average modified Mayo wrist score improved from 61.52±6.32 preoperatively to 85.88±8.37.Conclusion Arthroscopic autologous bone grafting with percutaneous cannulated screw and K-wires fixation is an effective and minimally invasive treatment for seaphoid nonunion,which could protect the blood supply of the fracture sites,decrease the surgical complications,promote bone healing and lead to a faster recovery.

Arthroscopic bone grafting with percutaneous fixation in treating scaphoid nonunion / 中华骨科杂志

Objective@#To analyze the clinical effects of arthroscopic autologous bone grafting and percutaneous fixation in treating scaphoid nonunion.@*Methods@#From May 2013 to August 2017, a total of 25 cases of patients including 20 males and 5 females with unilateral scaphoid fractures and nonunion were reviewed, with mean age of 35.80±2.41 years (18-65 years). The duration from injury to treatment was averaged 11.70±1.90 months (5-18 months). All of the cases sustained waist and proximal end fractures. X-ray and CT scan showed sclerosis and bone resorption without any callus at the fracture sites. However, there were no serious deformities and wrist arthritis. The patients suffered pain and weakness at the radial side of the wrist. The type of the fractures were Slade-Geissler's III-VI, including grade III 4 cases, grade IV 13 cases, grade V 7 cases and grade VI 1 case. The patients were treated with arthroscopic debridement of the sclerotic bone, autologous bone grafting, percutaneous screw (9 cases) or K-wires fixation (16 cases) and immobilization by plaster for 3 weeks after operation, followed by functional rehabilitation training. Bone union was assessed by serial plain radiographs and CT scan regularly. The functional effects were evaluated by comparing the modified Mayo wrist score with the visual analogue scale (VAS) for pain, range of motion (ROM) and the grip strength, which were measured before operation and at 18 months after operation.@*Results@#All cases were followed up. Bone union was achieved in all of 25 nonunion. The average radiological union duration was 10.24±2.10 weeks (6-20 weeks). The average VAS score decreased from 6.75±1.10 preoperatively to 1.33±0.21. The mean ROM of wrist was improved to 168.48°±12.41° (92.90% of that of the normal side), compared to that of 135.24°±17.47° preoperatively (79.80% of that of the normal side). The mean grip strength showed improvement from an average of 35.68±3.81 kg (80.46% of that of normal side) preoperatively to 48.75±4.42 kg (90.65% of that of normal side). The average modified Mayo wrist score improved from 61.52±6.32 preoperatively to 85.88±8.37.@*Conclusion@#Arthroscopic autologous bone grafting with percutaneous cannulated screw and K-wires fixation is an effective and minimally invasive treatment for scaphoid nonunion, which could protect the blood supply of the fracture sites, decrease the surgical complications, promote bone healing and lead to a faster recovery.

Diagnostic value of plasma procalcitonin for bacterial infection in patients receiving extracorporeal membrane oxygenation / 中华急诊医学杂志

Objective To evaluate the diagnostic value of plasma procalcitonin (PCT) for bacterial infection in patients receiving extracorporeal membrane oxygenation (ECMO). Methods Clinical data of patients receiving ECMO therapy admitted between August 2016 and January 2018 in Department of Critical Care Medicine, Tongji Hospital of Tongji Medical College were analyzed retrospectively. All patients receiving ECMO with bacterial culture were eligible for inclusion. Plasma PCT, IL-6, CRP and WBC levels detected within 24 h of bacterial cultures were analyzed immediately. Bacterial infection in ECMO was determined through bacterial culture and clinical characteristics. Finally, receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of inflammatory markers for bacterial infection in ECMO patients. Results Seventeen patients met the inclusion criteria, including 15 patients with acute respiratory failure and 2 patients with acute circulatory failure. There were 37 positive bacterial cultures, and 91 plasma PCT levels were detected in the process of ECMO. Compared with IL-6, CRP and WBC, plasma PCT had significant clinical significance in the diagnosis of bacterial infection (AUC=0.818, P<0.001). The cut-off value of PCT was 1.0 ng/mL, with a sensitivity of 92％ and a specificity of 43％. Conclusions Compared with other conventional inflammatory markers, plasma PCT has more diagnostic value for bacterial infection in ECMO patients.

Application of lateral thoracic wall vascular pedicled composite tissue flap in breast conserving surgery and remodeling breast shape / 中华内分泌外科杂志

Objective To introduce a breast conserving surgery for reconstruction of breast shape and to demonstrate the postoperative effect.Methods Ten patients were treated with this method from Apr.2016 to Dec.2017,and the lateral thoracic wall arteriovenous vessels were used as vascular pedicle to transfer the distal compound tissue flap of the blood vessel to repair the breast defect remnant cavity which was formed after the breast conserving surgery,and a good shape was obtained.Results All the 10 cases were successfully completed.The intraoperative bleeding was 20 to 30 ml.The operative time was 2 to 3 hours.No blood transfusion was needed.The average hospital stay was 11.5 days,ranging from 10 to 15 days.No infection happened to the incision.All the 10 patients were followed up from 2 to 20 months,with 11 months as the average.No limb edema,asymmetry or local recurrence happened.Conclusion The operation method is effective,safe and economical for patients with large swelling but strong desire to conserve breast.

The effect and mechanism of interfering the nicotinamide mononucleotide adenylyltransferase 1 gene in Parkinson's disease mouse models / 中华神经科杂志

Objective To investigate the effect and mechanism of interfering the nicotinamide mononucleotide adenylyltransferase 1(NMNAT1)gene in Parkinson's disease(PD)mouse models. Methods Thirty mice were randomly assigned to three groups: the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)group, the small interfering nicotinamide mononucleotide adenylyltransferase 1 (siNMNAT1)+MPTP group, and the control group, with 10 mice in each group.After injecting siRNA-green fluorescent protein(GFP)lentivirals directly into substantia nigra(SN),mice received intraperitoneal injections of MPTP, which was the siNMNAT1 +MPTP group.While the MPTP group was only with injections of MPTP,and the control group was with neither siRNA nor MPTP.Then we assessed the motor coordination ability firstly.To observe the variation of nigrostriatal pathway, the counts of dopamanergic neurons in SN were measured by tyrosine hydroxylase(TH)immunofluorescence staining.And the expression of TH in striatum, which was used to estimate the dopaminergic neurons axonal variation, was analyzed by RT-PCR.Then the expression of TH, SOD1, Bcl2, Bax, Bcl2/Bax in SN was estimated through Western blotting.Results Compared with the control group,the siNMNAT1+MPTP group and the MPTP group decreased significantly in motor coordination ability(creep down time: siNMNAT1 +MPTP group(62.8 ±15.7)s,MPTP group(77.9 ±13.5)s, control group(122.0 ±25.2)s), dopamanergic neuron counts(siNMNAT1 +MPTP group 45.0 ±6.7, MPTP group 68.0 ±11.3, control group 93.0 ± 12.8)and the striatal TH expression(Creep down time: t=-6.291, P=0.000; t=-4.865, P=0.000.Dopamanergic neuron counts:t=-10.482,P=0.000;t=-4.624, P=0.000.TH expression:t=-9.117,P=0.000;t=-5.716, P=0.000).Although the siNMNAT1+MPTP group showed lower coordination ability than the MPTP group, there was no statistically significant difference.Whereas the counts of dopamanergic neurons in SN(t=-5.487, P=0.000), the expression of TH in striatum(t=-5.146,P=0.003),SOD1(t=-4.143, P=0.001)and Bcl2/Bax(t=-6.303, P=0.000)were obviously decreased in the siNMNAT1+MPTP group,in which Bax increased significantly(t=3.550,P=0.002).Conclusions Interfering the expression of NMNAT1 aggravated the neurodegeneration in PD, and the mechanism might be related to oxidative stress and programmed cell death.

Risk factors analysis for the progression to castration-resistant prostate cancer / 中华泌尿外科杂志

Objective To explore risk factors of the progression to castration-resistant prostate cancer(CRPC)after hormone therapy (HT).Methods A total of 178 patients with prostate cancer from February 2009 to February 2018 were enrolled to analyze the risk factors of the progression to castrationresistant prostate cancer after androgen deprivation therapy in Fujian Medical University Union Hospital.The mean age was72 years (range,49-91 years);the middle Gleason score was 7 (range,4-10);the middle PSA at the initiation of HT was 24.45 ng/ml (range,0.16-100.0 ng/ml);the middle time to PSA nadir was 9 months (range,0.5-69.0 months);the middle PSA nadir after HT was 0.030 ng/ml (range,0.003-78.670 ng/ml);the mean hemoglobin level was 131 g/L (range,64-184 g/L);the mean alkaline phosphatase level was 98 U/L (range,35-734 U/L);39 patients were diabetes mellitus (21.9％);82 patients were bone metastasis/visceral metastasis (46.1％);85 patients (47.8 ％) were in clinical T1 + T2;93 patients(52.2％)were in clinical T3 + T4.We studied the relationship between CRPC and these risk factors including age,Gleason score,PSA at the initiation of HT,PSA nadir after HT,the time to PSA nadir,hemoglobin level,alkaline phosphatase,bone metastasis/visceral metastasis,clinical T stage,diabetes mellitus by x2 test,univariate and multivariate Cox regression analysis methods.Results The middle follow-up time was 30 months (range,6-92 months).There were 74 of 178 patients progressed to CRPC after HT.The median time of progression to CRPC in this cohort was 15 months (range,4-47 months).On x2 test analysis,there were statistically significant differences between the progression to CRPC group after HT and the rest group in Gleason score (P ＜0.001),PSA nadir after HT (P ＜0.001),PSA at the initiation of HT (P =0.042),alkaline phosphatase (P =0.002),bone metastasis/visceral metastasis (P＜0.001) and clinical T stage (P ＜0.001).Additionally,on multivariate Cox regression analysis,Gleason score (OR =6.152,P ＜ 0.001),PSA nadir after HT (OR =3.022,P ＜ 0.004) and the time to PSA nadir (OR =0.375,P ＜0.001) were found to be significantly associated with the rapid progression to CRPC.Conelusions Gleason score,PSA nadir after HT and the time to PSA nadir were significantly associated with the progression to CRPC.Patients with higher PSA nadir or the shorter time to PSA nadir were more likely to progress to CRPC.

Andrographolide-releasing collagen scaffold enhance the ability of chondrocytes to maintain their specific phenotype under inflammatory environment / 生物医学工程学杂志

The aim of this article is to study how andrographolide-releasing collagen scaffolds influence rabbit articular chondrocytes in maintaining their specific phenotype under inflammatory environment. Physical blending combined with vacuum freeze-drying method was utilized to prepare the andrographolide-releasing collagen scaffold. The characteristics of scaffold including its surface morphology and porosity were detected with environmental scanning electron microscope (ESEM) and a density instrument. Then, the release of andrographolide from prepared scaffolds was measured by UV-visible spectroscopy. Rabbit chondrocytes were isolated and cultured and seeded on andrographolide-releasing collagen scaffolds. Following culture with normal medium for 3 d, seeded chondrocytes were cultured with medium containing interleukin-1 beta (IL-1β) to stimulate inflammation for 7 d. The proliferation, morphology and gene transcription of tested chondrocytes were detected with Alamar Blue assay, fluorescein diacetate (FDA) staining and reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) test respectively. The results showed that the collagen scaffolds prepared by vacuum freeze-dry possess a high porosity close to 96%, and well-interconnected chambers around (120.7±17.8) μm. The andrographolide-releasing collagen scaffold continuously released andrographolide to the PBS solution within 15 d, and collagen scaffolds containing 2.22% andrographolide significantly inhibit the proliferation of chondrocytes. Compared with collagen scaffolds, 0.44% andrographolide-containing collagen scaffolds facilitate chondrocytes to keep specific normal morphologies following 7 d IL-1β induction. The results obtained by RT-qPCR confirmed this effect by enhancing the transcription of tissue inhibitor of metalloproteinase-1 ( ), collagen II ( ), aggrecan ( ) and the ratio of / collagen I( ), meanwhile, reversing the promoted transcription of matrix metalloproteinase-1 ( ) and matrix metalloproteinase-13 ( ). In conclusion, our research reveals that andrographolide-releasing (0.44%) collagen scaffolds enhance the ability of chondrocytes to maintain their specific morphologies by up-regulating the transcription of genes like , and , while down-regulating the transcription of genes like and which are bad for phenotypic maintenance under IL-1β simulated inflammatory environment. These results implied the potential use of andrographolide-releasing collagen scaffold in osteoarthritic cartilage repair.