AIM: To investigate the potential of human induced pluripotent stem cells(hiPSCs)differentiating into corneal epithelial cells in the simulated limbal stem cells(LSCs)microenvironment.METHODS: The hiPSC cell lines were established in vitro, and hiPSCs were co-cultured with corneal stromal cells in transwell system, which simulated the LSC microenvironment. Bone morphogenetic protein 4(BMP4)and a specific transforming growth factor β inhibitor(SB431542)were added to improve the differentiation efficacy. The expression of corneal epithelial cell-specific markers CK3 and CK12, corneal epithelial cell precursor CK15, and the limbal stem cell markers ABCG5 were determined by immunofluorescence staining and flow cytometry.RESULTS: The hiPSCs were actively proliferated in vitro, and immunofluorescence staining showed positive stem cell-specific markers OCT4, SOX2, TRA-1-60 and NANOG. Furthermore, hiPSCs co-cultured with corneal stromal cells exhibited LSCs markers ABCG5 and corneal epithelial cell precursor markers CK15 were positive; however, corneal epithelial cell markers CK3 and CK12 were negative. With the addition of BMP4 and SB431542, hiPSCs showed positive expression of CK3, and the CK3 expression increased over the time.CONCLUSION: With the addition of SB431542 and BMP4, hiPSCs cultured in simulated LSCs microenvironment could differentiate into corneal epithelial cells.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Multiple sclerosis is a severe autoimmune inflammatory disease mainly involving the central nervous system. In recent years, the exploration of the mechanism of nerve injury in multiple sclerosis has made great progress. At the same time, disease-modifying therapeutic drugs with different targets are also emerging. Understanding of the mechanisms of nerve injury in multiple sclerosis can help clinicians comprehensively understand the evolution of disease-modifying therapeutic targets of this disorder. Here, the mechanisms of nerve injury in multiple sclerosis and the relationship with the evolution of disease-modifying therapeutic targets are reviewed.

Resection is one of the most important treatments for esophageal squamous cell carcinoma, and routine postoperative follow-up is an effective method for early detection and treatment of recurrent metastases, which can improve patients' quality of life and prognosis. This consensus aims to provide a reference for colleagues responsible for postoperative follow-up of esophageal squamous cell carcinoma patients in China, and further improve the standardization of the diagnosis and treatment of esophageal squamous cell carcinoma.

Objective:To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection.Methods:This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes.Results:This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%, P>0.05) between cinepazide maleate group and control group. Conclusion:Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.

Objective:To investigate the clinical significance and the diagnostic value of detecting kidney injury biomarkers in urine and serum of children with Henoch-Sch?nlein purpura nephritis (HSPN).Methods:A total of 216 children with untreated HSPN, who were admitted in Beijing Children′s Hospital of Capital Medical University from January 2018 to December 2019, were recruited in this retrospective study. Two hundred and sixteen healthy children were selected as the healthy control group. We determined the levels of six biomarkers of kidney injury, including transferrin (TRF), immunoglobulin (IgG), microalbumin (mAlb), alpha-1 microglobulin (α1-MG), N-acetyl-β-D-glucosaminidase (NAG) in urine and cystatin C (CysC) in serum. The data from the two groups were analyzed, the diagnostic value of each biomarker was evaluated and a logistic regression model for the diagnosis of HSPN was established. In addition, 60 children with HSPN, who were admitted to our hospital from November 2021 to February 2022 and 60 healthy children, who underwent healthy check up in the same period were included to validate the diagnostic performance of the established logistic model. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of each biomarker.Results:The urine levels of TRF, IgG, mAlb, α1-MG and NAG and the serum level of CysC were significantly higher in the HSPN group than those in healthy control group (all P<0.05). The area under the ROC curve (AUC) of TRF, IgG, mAlb, α1-MG, NAG and the serum levels of CysC was 0.749, 0.719, 0.810, 0.648, 0.828 and 0.790 (all P<0.05). Logistics regression analysis showed that IgG, mAlb and TRF were the three diagnostic determinants of HSPN ( OR=1.083, 1.105, 1.704,all P<0.001), and the AUC was 0.916 of the established logistic model based on these three biomarkers. The sensitivity was 87.4% and the specificity reached 96.2%. The logistic model was validated by independent cohorts, and the AUC was 0.973, the sensitivity was 95.0% and the specificity was 98.3%. Conclusions:The levels of urine TRF, IgG, mAlb, α1-MG, NAG and serum CysC were higher in children with HSPN. The established logistic regression model based on three biomarkers including IgG, mAlb and TRF in this study has satisfactory clinical value in diagnosing HSPN in children.

Objective:To evaluate the safety and effectiveness of Kangduo endoscopic surgical robot system for partial nephrectomy.Methods:Consecutive patients with stage T 1 renal tumor meeting the inclusion criteria from the Department of Urology, Peking University First Hospital from December 2020 to February 2021 were prospectively enrolled. All patients underwent partial nephrectomy with the Kangduo endoscopic surgical robot system after signing the informed consent. Clinical data including preoperative, perioperative and postoperative pathology and follow-up were collected. Results:Among the 26 patients, there were 16 males and 10 females, with a median age of 53(33-74) years, and a median body mass index of 25.99(20.90-32.91) kg/m 2. There were 12 cases of left kidney tumor and 14 cases of right kidney tumor. The median tumor diameter was 2.2(1.0-3.5) cm. The median time of warm ischemia was 17.7(7.1-29.2) minutes, and all of them were less than 30 minutes. The median docking time was 4.7(2.3-9.9) minutes, and the median time of robotic arm operation was 65.0 (37.0-155.0) minutes. The median National Aeronautics and Space Administration Task Load Index (NASA-TLX) score was 5.3 (2.0-28.0), and no instrument-related adverse events occurred intraoperatively. The median postoperative hospital stay was 4 (4-5) days. All tumor margins were negative on pathologic reports. No Clavien Ⅱ stage operative complications occurred in all patients during perioperative period and 1 month after the surgery. Conclusions:The partial nephrectomy using the kangduo endoscopic surgical robot system were completed successfully, and no instrument-related adverse events and complications occurred, showing that this surgical system used for partial nephrectomy is safe and effective.

Objective:To study the clinical outcome of lamellar keratoplasty combined with autogenous corneal stromal padding for treatment of corneal perforation.Methods:An observational case series study was conducted.A total of 14 patients (14 eyes) with corneal perforation underwent lamellar keratoplasty in Henan Provincial People's Hospital from January 2017 to August 2018 were collected.During the operation, the corneal stromal autograft was taken to pad the corneal perforation.Visual acuity, intraocular pressure, corneal epithelial healing time, infection recurrence, and the status of corneal graft and anterior chamber were recorded on the 1st, 7th, 14th day, 1st, 3rd, 6th, 9th and 12th month after operation.OCT examination of anterior segment was performed at 1 month, 6 and 12 months postoperatively to observe the interlamellar structure of corneal implantation bed and stromal graft, anterior chamber and iris.The safety and effectiveness of the operation were evaluated according to the 1-year follow-up.The study protocol adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[18]). Written informed consent was obtained from each patient prior to entering the study cohort.Results:The healing time of corneal epithelium was 2-4 days after operation, (3.01±0.59) days on average.At one day after surgery, all patients had normal anterior chamber depth without aqueous leak and no double chamber was observed.The corneal grafts attached to the implantation bed well and showed mild to moderate edema.There was no recurrence of corneal infection ulcer two weeks after operation, and the corneal ulcer was healed and anterior chamber was well formed in 14 patients.The corneal graft was transparent, and the anterior segment OCT image showed corneal implant bed and graft were well attached, and the anterior chamber depth was normal three months after operation.The best corrected visual acuity of 9 eyes was more than 0.3 one year after operation, and the vision acuity of the 14 patients improved obviously, and no refractory glaucoma occurred after operation.Conclusions:Lamellar keratoplasty combined with autogenous corneal stromal padding is a safe and effective surgical procedure for treating corneal perforation.

Purpose: Bone destruction and pain caused by cancer is one of the most devastating complications of cancer patients with bone metastases, and it seriously affects the quality of patients’ life. Extracellular matrix metalloproteinase inducer (EMMPRIN) is a cell adhesion molecule with increased expression in a variety of tumors. This study focused to clarify the specific function of EMMPRIN in bone metastasis of breast cancer. Materials and Methods: Adenovirus with shRNA-EMMPRIN was transfected into MRMT-1 rat breast carcinoma cells, and the MRMT-1 cells with different expression levels of EMMPRIN were implanted into the bone marrow cavity of rat tibia. Next, the effect of down-regulation of EMMPRIN was evaluated as follows: bone damage was detected by X-ray radiological and tartrate-resistant acid phosphatase staining; the tumor burden was evaluated by hematoxylin and eosin staining; the test of pain-related behaviors was assessed used the bilateral paw withdrawal mechanical threshold; and the levels of secretory factors in tumor conditioned medium were determined by using enzyme-linked immunosorbent assay. Results: We found that down-regulation of EMMPRIN in tumor cells can simultaneously reduce tumor burden, relieve cancer-induced bone destruction and pain. Conclusion: Materials and Methods EMMPRIN is expected to be a therapeutic target for relieving bone metastasis of breast cancer and alleviating cancerinduced bone destruction and pain. The method of targeting EMMPRIN may be a promising strategy for the treatment of cancer in the future.