INTRODUCTION: Obstructive sleep apnoea (OSA) is a serious but underdiagnosed condition. Demand for the gold standard diagnostic polysomnogram (PSG) far exceeds its availability. More efficient diagnostic methods are needed, even in tertiary settings. Machine learning (ML) models have strengths in disease prediction and early diagnosis. We explored the use of ML with oximetry, demographic and anthropometric data to diagnose OSA. METHODS: A total of 2,996 patients were included for modelling and divided into test and training sets. Seven commonly used supervised learning algorithms were trained with the data. Sensitivity (recall), specificity, positive predictive value (PPV) (precision), negative predictive value, area under the receiver operating characteristic curve (AUC) and F1 measure were reported for each model. RESULTS: In the best performing four-class model (neural network model predicting no, mild, moderate or severe OSA), a prediction of moderate and/or severe disease had a combined PPV of 94%; one out of 335 patients had no OSA and 19 had mild OSA. In the best performing two-class model (logistic regression model predicting no-mild vs. moderate-severe OSA), the PPV for moderate-severe OSA was 92%; two out of 350 patients had no OSA and 26 had mild OSA. CONCLUSION Our study showed that the prediction of moderate-severe OSA in a tertiary setting with an ML approach is a viable option to facilitate early identification of OSA. Prospective studies with home-based oximeters and analysis of other oximetry variables are the next steps towards formal implementation.
Humans ; Oximetry/methods* ; Sleep Apnea, Obstructive/diagnosis* ; Male ; Female ; Middle Aged ; Machine Learning ; Polysomnography ; Adult ; Anthropometry ; ROC Curve ; Aged ; Algorithms ; Predictive Value of Tests ; Sensitivity and Specificity ; Neural Networks, Computer ; Demography

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

[Purpose]To investigate the trends of incidence and age at onset of uterine corpus can-cer in Jiangsu cancer registration areas from 2009 to 2019.[Methods]The continuous monitoring data of uterine corpus cancer from 2009 to 2019 were collected from 16 cancer registries in Jiang-su Province.The crude incidence rate,the age-standardized incidence rate by Chinese standard population(ASIRC),crude and adjusted mean age,and standardized age-specific incidence composition were calculated.The average annual percentage change(AAPC)were analyzed by the Joinpoint regression model.The linear regression model was used to analyze the relationship be-tween mean age at onset and year.The standardized age-specific incidence composition in 2009 and 2019 were compared.[Results]The ASIRC of uterine corpus cancer in all registration areas and in rural areas of Jiangsu Province showed upward trends with AAPC of 1.78％and 2.38％,re-spectively(P＜0.05),but not showed in the urban areas(AAPC=1.30％,P＞0.05).The crude mean age at onset increased from 56.48 years old in 2009 to 58.26 years old in 2019 with an average annual growth of 0.173 years old(P=0.001).After the population structure standardized,the trends disappeared in all registration areas.[Conclusion]From 2009 to 2019,the standardized incidence rates of uterine corpus cancer were on rise in Jiangsu cancer registration areas,especially in the age group of 50 to 59 years old.

Humans ; Cardiovascular Diseases/chemically induced* ; East Asian People ; Risk Factors ; Heart Disease Risk Factors ; Lipids ; Anticholesteremic Agents/adverse effects* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Treatment Outcome

Humans ; Spinal Diseases/surgery* ; Spine/surgery*

[摘 要] 目的：探究炎症标志物对晚期非小细胞肺癌（NSCLC）患者抗PD-1治疗疗效及安全性的预测价值。方法：动态监测2018年1月至2020年12月在海军军医大学第一附属医院接受抗PD-1治疗的222例晚期NSCLC患者的血清炎症标志物，应用ROC曲线计算最佳截断值并将炎症指标分为高和低水平两组。以Log-Rank检验和Kaplan-Meier法分析患者临床病理特征及各炎症标志物水平与患者预后的关系，单因素和多因素Cox回归分析估算PFS和OS的风险比。Fisher精确检验分析各炎症标志物基线水平高和低两组与免疫相关不良反应（irAE）的相关性，Wilcoxon秩和检验比较治疗前（基线）与首次PR、PD时及发生irAE时各炎症标志物水平的差异。结果：血清炎症标志物NLR、MLR、PLR、LDH、CRP和IL-6基线水平升高与患者的PFS和OS显著缩短有关（圴P<0.01）。多因素分析结果显示，基线升高的PLR、MLR和LDH是PFS和OS的独立危险因素（P<0.05或P<0.01）。NLR、LDH、CRP和IL-6水平在患者首次获得PR时显著降低（P<0.05或P<0.01），LDH、CRP、IL-6和TNF-α水平在出现PD时显著升高（P<0.05或P<0.01）。发生irAE时，LDH、CRP、IL-6、IL-10和TNF-α水平与基线水平相比显著升高（P<0.05或P<0.01）。结论：晚期NSCLC抗PD-1治疗中炎症标志物水平的下降提示患者病情改善，其水平的上升则提示病情进展且与irAE的发生相关，动态监测炎症标志物可以预测抗PD-1治疗的疗效及安全性，有助于筛选抗PD-1治疗的最佳晚期NSCLC人群。

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

Objective To explore the application of UW solution in the replantation of the rat limb,and to explore a simple method for the ideal preservation of the amputated limbs.Methods From September,2017 to Janurary,2018,one hundred and twenty healthy adult male SD rats,weight 320-350 g,were randomly divided into 8 groups:A,B,C,D,E,F,G,H group.The isolated limbs of the control group A,C,E,G were cryopreserved in refrigerator at 4 ℃,while those of the experiment group B,D,F,H were preserved under the same condition after being perfused with UW solution.All the severed limbs were replanted back to the rats after different time length of cry opreservation:A,B 12 hours,C,D 20 hours,E,F 28 hours and G,H 36 hours.During the operations the femoral artery and venous patency were detected immediately after anastomosis.And after the operations the survival rates of limb replantation were observed.On the third day after the limb replantation,the tibial posterior muscle tissue was examined for pathology.The cell areas in pathological photographs were compared with Image analysis software Image-pro Plus 6.0 and the ultra structural changes of skeletal muscle tissue were observed.Results The femoral artery and venous patency in experiment group A,C,E and control group B,D,F were all 100 percent.However,in the group G,H the severed limb vessels changed obviously,the patency dropped markedly and the survival rates of limb replantation turned out to be 0.The experiment groups perfused with UW solutions,had relatively higher survival rates compared with the control groups (12 h:93.33％ vs.53.33％,20 h:80.00％ vs.40.00％,28 h:53.33％ vs.13.33％) and the skeletal muscles edema was lighter than that of the control group,with a larger proportion of cell areas(12 h:69.49±8.57 vs.44.75±6.34,20 h:56.34±7.73 vs.36.69±5.74,28 h:45.76±8.23 vs.31.49±7.72).There was a significantly difference (P＜0.05).Electron microscope observation showed that the experiment group bore a lighter damage of myofibril,interstitial tissue and mitochondria compared with the control group.Conclusion The combination of UW solution and cryopreservation of organs is an ideal and proper way to preserve the amputation limb,to extend the time limit for replantation,and to achieve a better recovery effect of postoperative limb function.Besides,UW solution is easy to be promoted in the treatment of isolated limb in clinical work.

Phytochemical investigation on Ilex asprella stems by using various chromatographic techniques led to the isolation of 18 phenolic constituents. Based on spectroscopic data analyses and/or comparison of the spectroscopic data with those in literature, these constituents were identified, including two lignans (1, 2), five phenylpropanes (3-7), six chlorogenic analogues (8-13), and five benzoic analogues (14-18). Among them, compounds 3-7, 9, 11, 13, 14, 17, and 18 were isolated from genus Ilex for the first time, and 2, 8, 10, 15, and 16 were isolated from this species for the first time. The in vitro anti-inflammatory assay results showed that compounds 8, 9, 11, 13, and 15 possessed moderate inhibition on the NO production in RAW264.7 cells with IC₅₀ values of 51.1-85.8 μmol·L⁻¹. The present study brought preliminary reference for the clarification of therapeutic ingredients of I. asprella with anti-inflammatory efficacy and its quality evaluation.
Animals ; Anti-Inflammatory Agents ; isolation & purification ; pharmacology ; Ilex ; chemistry ; Mice ; Nitric Oxide ; metabolism ; Phenols ; chemistry ; Phytochemicals ; isolation & purification ; pharmacology ; Plant Stems ; chemistry ; RAW 264.7 Cells

Phytochemical investigation on the stems of Ilex asprella by using various chromatographic techniques led to the isolation of 13 compounds. By spectroscopic analyses and comparisons the spectral data with those in literatures, these compounds were identified as salicifoneoliganol(1), rel-(7R,8S)-3,3',5-trimethoxy-4',7-epoxy-8,5'-neolignan-4,9,9'-triol 9-β-D-glucopyranoside(2),(+)-cycloolivil(3),(+)-syringaresinol-4'-O-β-D-monoglucoside(4), liriodendrin(5), caffeic acid (6), 3,4-dihydroxy-5-methoxybenzaldehyde(7), benzene-1,2,4-triol(8), 3,4,5-trimethoxyphenyl-1-O-β-D-apiofuranosyl(1″→6')-glucopyranoside(9), aeculetin(10), cryptochlorogenic acid ethyl ester(11), chlorogenic acid ethyl ester(12), and rel-5-(3S,8S-dihydroxy-1R,5S-dimethyl-7-oxa-6-oxobicyclo [3,2,1]oct-8-yl)-3-methyl-2Z,4E-pentadienoic acid(13). Among them, compounds 7, 8, 11, and 13 were isolated from genus Ilex for the first time, and 1-3, 9, 10, and 12 were isolated from this speciesfor the first time. The anti-inflammatory assay results of these compounds showed that compounds 1 and 9 showed moderate inhibitory effect against NO production in RAW 267. 4 cells with IC₅₀ values of 35.7 and 50.6 μmol•L⁻¹, in vitro respectively, whereas compound 10 showed weak inhibition(IC₅₀ value 98.7 μmol•L⁻¹).