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Additional file 1: Materials and Methods. Fig. S1. Identification of EpiSCs from human prepuce. Fig. S2. EpiSCs (P4) were stained with CM-Dil. Fig. S3. The mRNA sequencing results of EpiSCs. (A) Relationship between up-regulated and down-regulated genes of DEGs in different groups. (B) KEGG functional classification of the DEGs. Fig. S4. The organs of the NaCl group and the EpiSC group. Table S1. The proliferation curve of EpiSCs. Quality control data (Fig. S5. Statistical results of cell viability before and after cryopreservation. Fig. S6. Effect of high temperature on epidermal cells. Fig. S7. Effect of low temperature on epidermal cells. Fig. S8. Effect of long-term experiment on epidermal cells. Fig. S9. Detection of CD73, CD90, and CD105 expression in EpiSCs (P8) by flow cytometry. Table S2. Items and standards for testing the quality of EpiSCs.

BackgroundPersistent critical illness (PerCI) is an immunosuppressive status. The underlying pathophysiology driving PerCI remains incompletely understood. The objectives of the study were to identify the biological signature of PerCI development, and to construct a reliable prediction model for patients who had suffered orthopedic trauma using machine learning techniques.MethodsThis study enrolled 1257 patients from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Lymphocytes were tracked from ICU admission to more than 20 days following admission to examine the dynamic changes over time. Over 40 possible variables were gathered for investigation. Patients were split 80:20 at random into a training cohort (n=1035) and an internal validation cohort (n=222). Four machine learning algorithms, including random forest, gradient boosting machine, decision tree, and support vector machine, and a logistic regression technique were utilized to train and optimize models using data from the training cohort. Patients in the internal validation cohort were used to validate models, and the optimal one was chosen. Patients from two large teaching hospitals were used for external validation (n=113). The key metrics that used to assess the prediction performance of models mainly included discrimination, calibration, and clinical usefulness. To encourage clinical application based on the optimal machine learning-based model, a web-based calculator was developed.Results16.0% (201/1257) of all patients had PerCI in the MIMIC-III database. The means of lymphocytes (%) were consistently below the normal reference range across the time among PerCI patients (around 10.0%), whereas in patients without PerCI, the number of lymphocytes continued to increase and began to be in normal range on day 10 following ICU admission. Subgroup analysis demonstrated that patients with PerCI were in a more serious health condition at admission since those patients had worse nutritional status, more electrolyte imbalance and infection-related comorbidities, and more severe illness scores. Eight variables, including albumin, serum calcium, red cell volume distributing width (RDW), blood pH, heart rate, respiratory failure, pneumonia, and the Sepsis-related Organ Failure Assessment (SOFA) score, were significantly associated with PerCI, according to the least absolute shrinkage and selection operator (LASSO) logistic regression model combined with the 10-fold cross-validation. These variables were all included in the modelling. In comparison to other algorithms, the random forest had the optimal prediction ability with the highest area under receiver operating characteristic (AUROC) (0.823, 95% CI: 0.757-0.889), highest Youden index (1.571), and lowest Brier score (0.107). The AUROC in the external validation cohort was also up to 0.800 (95% CI: 0.688-0.912). Based on the risk stratification system, patients in the high-risk group had a 10.0-time greater chance of developing PerCI than those in the low-risk group. A web-based calculator was available at https://starxueshu-perci-prediction-main-9k8eof.streamlitapp.com/.ConclusionsPatients with PerCI typically remain in an immunosuppressive status, but those without PerCI gradually regain normal immunity. The dynamic changes of lymphocytes can be a reliable biomarker for PerCI. This work developed a reliable model that may be helpful in improving early diagnosis and targeted intervention of PerCI. Beneficial interventions, such as improving nutritional status and immunity, maintaining electrolyte and acid-base balance, curbing infection, and promoting respiratory recovery, are early warranted to prevent the onset of PerCI, especially among patients in the high-risk group and those with a continuously low level of lymphocytes.

Xuedong Shi,1,* Yaosheng Liu,2,* Yunpeng Cui,1 Haifeng Qin,3 Shaoxing Yang,3 Mingxing Lei4 1Department of Orthopedic Surgery, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Orthopedic Surgery, The Fourth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Pulmonary Neoplasms Internal Medicine, The Fifth Medical Center of the Chinese PLA General Hospital, Beijing, People’s Republic of China; 4Department of Orthopedic Surgery, Hainan Hospital of Chinese PLA General Hospital, Sanya, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yaosheng LiuDepartment of Orthopedic Surgery, The Fourth Medical Center of Chinese PLA General Hospital, No. 8, Fengtaidongda Road, Beijing 100071, People’s Republic of ChinaTel/Fax +86-10-66947017Email 632763246@qq.comPurpose: The study aims to investigate and compare the efficacy and safety of intraoperative 125I implantation and postoperative irradiation after surgical decompression and stabilization in the treatment of patients with metastatic epidural spinal cord compression (MESCC).Methods: The study retrospectively enrolled 122 MESCC patients treated with surgical decompression and pedicle stabilization combined with 125I brachytherapy (the brachytherapy group) or postoperative radiotherapy (the irradiation group). Operation time, intraoperative blood loss, pain relief, postoperative ambulatory status, postoperative survival outcome, complications, and length of hospitalization were collected and compared between the two groups. Ten potential risk factors were analyzed for postoperative survival outcome.Results: No significant difference was found in baseline characteristics between the two groups (P> 0.05). Postoperative VAS score was significantly decreased, as compared with preoperative scores in both groups (P˂0.001). The VAS in the brachytherapy group was significantly lower than that in the irradiation group at postoperative 1 month, 3 months, and 6 months (P˂0.05). The postoperative ambulatory rates were 90.0% (54/60) in the brachytherapy group and 83.9% (52/62) in the irradiation group (P=0.32). The median overall survival time was similar between the two groups (7.43 months vs 7.27 months, P=0.37). Of all patients in the brachytherapy group, 25.0% (15/60) of patients suffered from complications, while 46.8% (29/62) of patients had complications in the irradiation group (P=0.0086). According to the multiple Cox regression, primary sites (P=0.038), ECOG performance status (P=0.014), and visceral metastases (P=0.0016) showed significance for postoperative survival outcome.Conclusion: Surgical decompression and spine stabilization combined with 125I brachytherapy is a relatively safe and useful method in MESCC patients.Keywords: metastatic epidural spinal cord compression, 125I brachytherapy, radiotherapy, surgical decompression and spine stabilization, prognosis

Yunpeng Cui,1,* Yuanxing Pan,1,* Mingxing Lei,2 Chuan Mi,1 Bing Wang,1 Xuedong Shi1 1Department of Orthopedic Surgery, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Orthopedic Surgery, Hainan Hospital of Chinese PLA General Hospital, Sanya, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xuedong ShiDepartment of Orthopedic Surgery, The Peking University First Hospital No. 8 Xishiku Street, Xicheng District Beijing 100032 People’s Republic of ChinaTel +86-010-83572211Email 172998774@qq.comPurpose: This study aims to develop an algorithm to predict cement injection volumes in patients with spine metastases treated with percutaneous vertebroplasty (PVP). Risk factors were also analyzed for intra-spinal canal cement leakages.Patients and Methods: A retrospective analysis of 584 vertebrae in 251 patients. Patients and vertebrae were divided into three groups based on grades of tumor invasion to the spinal cord. Patients with the complete posterior wall of vertebrae were classified into group A, patients without the complete posterior wall of vertebrae but with normal Dural sac were classified into group B, and patients with deformation of the Dural sac but without neurological symptom were classified into group C. We systematically reviewed demographic data, clinical parameters, radiology features, and cement leakages among the three groups. The multiple linear regressions were used to screen potential risk factors and develop the algorithm to predict injected cement volumes in vertebrae. Significant factors were included in the algorithm. Potential risk factors for intra-spinal canal cement leakage were analyzed using the multiple logistic regressions.Results: In the study, 17.1% (100/584) of vertebrae occurred cement leakages. Vertebrae in group C (28.6%, 8/28) had the highest cement leakage rate than patients in group A (14.4%, 61/424) and B (23.5%, 31/132) (P=0.014). Vertebrae in group C (14.3%, 4/28) were also more prone to intra-spinal canal leakages (P=0.003). The multiple logistic analysis showed that the Bilsky scale was significantly associated with intra-spinal canal cement leakages (P< 0.001). The multiple linear regression analysis showed that intercept (P< 0.001), treated vertebrae level (P< 0.001), cortical osteolytic destruction in posterior wall (P< 0.001), and Bilsky scale (P=0.014) were significant and those variables were included in the algorithm. The algorithm was Y=3.1627－0.8677×treated vertebrae level－0.6182×cortical osteolytic destruction in the posterior wall－0.2819×Bilsky scale.Conclusion: An algorithm is proposed and can be used to calculate cement injection volumes in spine metastases treated with PVP. This algorithm can facilitate surgical planning and guide cement injections. Bilsky scale is an independent risk factor for intra-spinal canal cement leakages. We do not recommend PVP treated in patients with a Bilsky scale of 2 and 3 mainly due to a high rate of intra-spinal canal cement leakages.Keywords: spinal metastases, percutaneous vertebroplasty, algorithm, intra-spinal canal leakages, risk factors

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Additional file 1. Table S1 Characteristic comparison between the training and validation group. Table S2 COX regression analysis of total patients.

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Abutment pressure distribution is different when a longwall panel is passing through the abandoned gate roads in a damaged coal seam. According to the geological condition of panel E13103 in Cuijiazhai Coal Mine in China, theoretical analysis and finite element numerical simulation were used to determine the front pressure distribution characteristics when the longwall face is 70, 50, 30, 20, 10, and 5 m from the abandoned roadways. The research results show that the influence range of abutment pressure is 40 to 45 m outby the face, and the peak value of front abutment pressure is related to the distance between the face and abandoned roadways. When the distance between the longwall face and abandoned roadways is reduced from 50 to 10 m, the front abutment pressure peak value kept increasing. When the distance is 10 m, it has reached the maximum. The peak value is located in 5 to 6 m outby the faceline. When the distance between the longwall face and abandoned roadways is reduced from10 to5 m, the front abutment pressure sharply decreases, the intact coal yields and is even in plastic state. The peak value transfers to the other side of the abandoned roadways. The research results provide a theoretical basis for determining the advance support distance of two roadways in the panel and the reinforcement for face stability when the longwall face is passing through the abandoned roadways. Keywords: Abandoned roadways, Abutment pressure, Theoretical calculation, Numerical simulation

Additional file 1. Questionnaire on mental distress among medical graduate students of China.