Macrophages and kidney transplantation / 器官移植

Kidney transplantation is the optimal treatment for patients with end-stage renal disease, whereas long-term survival of renal allografts remains a challenging issue. Renal ischemia-reperfusion injury (IRI) and rejection of renal allografts are considered as important influencing factors of long-term survival of renal allografts, which are regulated by innate and adaptive immune cells. Macrophages are one type of innate immune cells that could assist initiating adaptive immunity and are divided into M1, M2 and regulatory macrophages. Previous studies have revealed that M1 macrophages may aggravate renal IRI and acute T cell-mediated rejection (TCMR). However, M2 macrophages may mitigate renal IRI and acute TCMR, whereas it is positively correlated with antibody-mediated rejection (AMR). Regulatory macrophages are a special subgroup of macrophages, which may induce immune tolerance in organ transplantation and have promising clinical application prospects and basic scientific research value. In this article, the relationship among macrophage typing, macrophages and renal IRI, rejection of renal allografts, regulatory macrophages and immune tolerance was reviewed, and the potential mechanism was analyzed, aiming to induce changes in macrophage subtypes or eliminate specific subtypes of macrophages, thereby improving clinical prognosis of the recipients and long-term survival of renal allografts.

The Mechanism of miR-1294 Targeting SOX15 to Regulate Wnt/β-catenin Signaling Pathway and Promote the Proliferation of Acute Lymphoblastic Leukemia Cells in Children / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of abnormal miRNA expression on the proliferation of pediatric acute lymphoblastic leukemia (ALL) cells and its related mechanism.@*METHODS@#15 children with ALL and 15 healthy subjects were collected from the Second Affiliated Hospital of Hainan Medical University from July 2018 to March 2021. MiRNA sequencing was performed on their bone marrow cells, and validated using qRT-PCR. MiR-1294 and miR-1294-inhibitory molecule (miR-1294-inhibitor) were transfected into Nalm-6 cells, and the proliferation of Nalm-6 cells was detected by CCK-8 and colony formation assays. Western blot and ELISA were used to detect apoptosis of Nalm-6 cells. Biological prediction of miR-1294 was performed to find the target gene, which was verified by luciferase reporter assay. Si-SOX15 was transfected into Nalm-6 cells, Western blot was used to detect the expression of Wnt signaling pathway-related proteins and to verify the effect of si-SOX15 on the proliferation and apoptosis of Nalm-6 cells.@*RESULTS@#Compared with healthy subjects, 22 miRNAs were significantly upregulated in bone marrow cells of ALL patients, of which miR-1294 was the most significantly upregulated. In addition, the expression level of SOX15 gene was significantly reduced in bone marrow cells of ALL patients. Compared with the NC group, the miR-1294 group showed increased protein expression levels of Wnt3a and β-catenin, faster cell proliferation, and more colony-forming units, while caspase-3 protein expression level and cell apoptosis were reduced. Compared with the NC group, the miR-1294-inhibitor group showed reduced protein expression levels of Wnt3a and β-catenin, slower cell proliferation, and fewer colony-forming units, while caspase-3 protein expression level was increased and apoptosis rate was elevated. miR-1294 had a complementary base-pair with the 3'UTR region of SOX15 , and miR-1294 directly targeted SOX15 . The expression of miR-1294 was negatively correlated with SOX15 in ALL cells. Compared with the si-NC group, the si-SOX15 group showed increased protein expression levels of Wnt3a and β-catenin, accelerated cell proliferation, and decreased caspase-3 protein expression level and cell apoptosis rate.@*CONCLUSION@#MiR-1294 can target and inhibit SOX15 expression, thus activating the Wnt/β-Catenin signaling pathway to promote the proliferation of ALL cells, inhibit cell apoptosis, and ultimately affect the disease progression.

Analysis of major adverse cardiac events and risk factors during perioperative period of cervical spine surgery / 中国综合临床

Objective:To understand the occurrence of major adverse cardiac events (MACE) during the perioperative period of cervical spine surgery and analyze its risk factors.Methods:A retrospective analysis of 426 cervical spine surgery patients admitted to the from March 2017 to March 2021. The basic information of the patients, including gender, age, body mass index (BMI), underlying diseases, and the Charlson comorbidity index (CCI) was calculated based on the underlying diseases.The preoperative serum cardiac troponin I(cTnI) level and the operation-related indicators were collected,including the type of cervical spine surgery, surgical procedure, approach, duration of surgery, duration of anesthesia, intraoperative bleeding, postoperative pain visual analogue scale (VAS), and electrolyte disturbances. Count data were expressed as cases (%), and comparisons between groups were made using the χ 2 test; logistic regression models were applied to perform a multifactorial analysis of the factors influencing the perioperative occurrence of MACE in patients undergoing cervical spine surgery. Results:Among the 426 patients, 54 (12.68%) experienced MACE during the perioperative period, including 4 cases of unstable angina (7.41%), 4 cases of acute myocardial infarction (7.41%), 33 cases of severe arrhythmia (61.11%), and 13 cases of acute heart failure (24.07%). The results of multivariate logistic regression analysis showed that the older the age group (50-59 years old: odds ratio=1.34, 95% confidence interval: 1.14-1.78; 60-69 years old: odds ratio=1.48, 95% confidence interval: 1.20-1.86; 70-79 years old: odds ratio=1.71, 95% confidence interval: 1.34-2.57; 80-89 years old: odds ratio=1.95, 95% confidence interval: 1.46-2.85), as well as females, CCI scores>3, and preoperative cTnI>0.04 μg/L, postoperative VAS score>5, and electrolyte disorders are all influencing factors for the occurrence of MACE in cervical spine surgery patients during the perioperative period (odds ratios of 1.84, 2.12, 2.34, 2.57, 2.20, 95% confidence intervals of 1.34-2.68, 1.50-3.41, 1.63-3.72, 1.53-4.01, 1.43-3.69, all P<0.05). Conclusions:The incidence of MACE in the perioperative period of cervical spine surgery is relatively high. Elderly age, female, high CCI score, high preoperative serum cTnI, postoperative pain and electrolyte disturbance are independent risk factors for the perioperative period of cervical spine surgery.

Short-term efficacy of laparoscopic surgery after short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy for locally advanced rectal cancer: a prospective study / 中华消化外科杂志

Objective:To investigate the short-term efficacy of laparoscopic surgery after short-course radiotherapy followed by sequential chemotherapy combined with anti-programmed death-1 (PD-1) antibody therapy for locally advanced rectal cancer.Methods:The prospective study was conducted. The clinicopathological data of 30 locally advanced rectal cancer patients who were admitted to the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology from November 2019 to September 2020 were selected. Patients underwent laparos-copic surgery after short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy. Observation indicators: (1) situations of the enrolled patients; (2) situations of short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy and adverse events; (3) preoperative evaluation and surgical situations; (4) postoperative situations and pathological examinations; (5) postoperative adjuvant chemo-therapy and follow-up. Follow-up was conducted using outpatient examination and telephone interview up to March 2022. Patients were followed up once every 3 weeks during the period of short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy to detect the adverse events and patients were followed up once every 3 months during the first postoperative 2 years and once every 6 months thereafter to detect tumor recurrence and survival of patients. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results:(1) Situations of the enrolled patients. A total of 30 patients were selected for eligibility. There were 17 males and 13 females, aged (57±16)years. Cases with preoperative primary tumor in stage cT3 and cT4 were 22 and 8, respectively. Cases with preoperative clinical lymph node metastasis in stage cN0, cN1, cN2 were 4, 16, 10, respectively. Cases in preoperative clinical stage Ⅱ and Ⅲ were 4 and 26, respectively. Of the 30 patients, there were 21 cases with positive circumferential margin and 12 cases with vascular invasion in extramural of rectum in the preoperative imaging evaluation. Distance from the distal margin of tumor to anal margin and tumor diameter of the 30 patients were 4.7(range, 1.9?9.0)cm and 5.4(range, 2.1?10.0)cm, respectively. There were 28 cases with mismatch repair proficient and 1 case with mismatch repair deficiency in tumor tissues. There was 1 case missing the data of mismatch repair in tumor tissues as failed in biopsy of pathological examination before the treatment. (2) Situations of short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy and adverse events. All the 30 patients completed preoperative short-course radiotherapy successfully. Of the 30 patients, there were 3 cases not undergoing the sequential chemotherapy combined with anti-PD-1 antibody therapy and there were 24 cases undergoing 2 courses of the sequential chemotherapy combined with anti-PD-1 antibody therapy and 3 cases undergoing 1 course of the sequential chemotherapy combined with anti-PD-1 antibody therapy. The time interval between ending of radiotherapy and starting of chemotherapy combined with anti-PD-1 antibody therapy of the 27 patients was 12(range, 4?18) days. Cases with leukopenia, cases with endothelial hyperplasia of skin capillaries, cases with radiation proctitis, cases with anemia, cases with peripheral neurotoxicity, cases with neutropenia, cases with thrombocytopenia, cases with fatigue, cases with anorexia, cases with abnormal liver function, cases with hypothyroidism were 24, 22, 21,20, 18, 16, 16, 13, 10, 9, 2 in the 30 patients during the preoperative short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy. Cases with the above adverse events were improved after symptomatic treatment. (3) Preoperative evaluation and surgical situations. Seven of the 30 patients were in clinical complete remission after preoperative multidisciplinary evaluation and the other 23 patients were not in clinical complete remission. Twenty-seven of the 30 patients underwent laparoscopic radical resection of rectal cancer and 3 patients not undergoing the sequential chemotherapy combined with anti-PD-1 antibody therapy did not undergo surgery. The time interval between ending of chemotherapy combined with anti-PD-1 antibody therapy and the surgery of the 27 patients were 14(range, 5?141)days. Of the 27 cases, there were 13 cases and 14 cases with 0 and 1 of the preoperative Eastern Cooperative Oncology Group score, respectively, and there were 24 cases undergoing low anterior proctectomy and 3 cases undergoing abdominoperineal excision. The operation time and volume of intra-operative blood loss of the 27 cases were (182±36)minutes and 30(range, 10?150)mL, respectively. Of the 27 cases, there were 16 cases with protective ileostomy and 24 cases with anal preservation. (4) Postoperative situations and pathological examinations. The time to postoperative first flatus, time to postoperative initial liquid food intake and duration of postoperative hospital stay of the 27 patients undergoing surgery were 2(range, 1?4)days, 3(range, 2?5)days and 8(range, 7?16)days, respectively. Five of the 27 patients had postoperative grade Ⅰ?Ⅱ complications, including 2 cases with incision infection, 1 case with abdominal infection, 1 case with incision hemorrhage and 1 case with venous thrombosis in left lower limb intermuscular. Cases with postoperative complica-tions were improved after symptomatic treatment. Results of postoperative pathological examina-tion showed that the rate of pathologic complete response in 27 patients was 48.1%(13/27). Of the 27 cases, cases in grade 0, grade 1, grade 2, grade 3 of the tumor regression grading were 13, 5, 7, 2, respectively, cases in stage T0, stage Tis, stage T2, stage T3 of the tumor T staging were 13, 1, 5, 8, respectively, cases in stage N0, stage N1, stage N2 of the tumor N staging were 19, 6, 2, respectively, cases in stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲ of the tumor TNM staging were 14, 0, 5, 8, respectively. The number of lymph node dissected of the 27 patients was 15(range, 3?29). Of the 27 patients, there was 1 case with positive circumferential margin and 26 cases achieving R 0 resection. None of the 27 patients underwent secondary operation or perioperative death. (5) Postoperative adjuvant chemotherapy and follow-up. Of the 27 patients undergoing surgery, 21 cases underwent post-operative adjuvant chemotherapy, with the cycles of 4(range, 1?6). All the 27 patients were followed up for 20(range, 20?29)months. During the follow-up, 3 cases not achieving pathological complete response had tumor recurrence and no patient died. The disease free survival rate of the 27 patients was 88.9%. Conclusion:Laparoscopic surgery after short-course radiotherapy followed by sequential chemotherapy combined with immunotherapy for locally advanced rectal cancer is safe and feasible, with satisfied short-term efficacy.

Effects of moderate dose rosuvastatin on carotid plaque in patients with diabetes mellitus evaluated by magnetic resonance imaging / 中华心血管病杂志

Objective: To observe the effect of lipid regulating therapy on carotid atherosclerotic plaque in diabetic patients. Methods: The REACH study, conducted between March 2009 and February 2012, enrolled asymptomatic patients with magnetic resonance imaging (MRI) confirmed carotid atherosclerotic plaque, who had never taken lipid-lowering drugs. Patients were treated with a moderate dose of rosuvastatin for 24 months. Blood lipid levels were measured and carotid MRI was performed at baseline, 3 and 24 months after treatment. The volume of carotid wall and lipid-rich necrotic core (LRNC) were measured by image analysis software. This study retrospectively analyzed patients in the REACH study. Patients were divided into diabetes group and non-diabetic group. The changes of blood lipid level and MRI parameters of carotid atherosclerotic plaque were compared between the two groups and their correlation was analyzed. Results: A total of 38 patients with carotid atherosclerotic plaque were included in this study, including 13 patients (34.2%) in the diabetic group and 25 patients (65.8%) in the non-diabetic group. Baseline parameters were comparable between the two groups, except higher HbA1c level in diabetes group (P<0.05). Compared with baseline, the total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels were significantly decreased at 3 and 24 months in both two groups (P<0.05). The change of high-density lipoprotein cholesterol (HDL-C) in diabetes group was not obvious, while it was significantly increased in non-diabetic group at 24 months ((1.38±0.33) mmol/l vs. (1.26±0.26) mmol/l, P<0.05). MRI results showed that the volume and percentage of LRNC remained unchanged at 3 months, slightly decreased at 24 months (64.86 (45.37, 134.56) mm3 vs. 75.76 (48.20, 115.64) mm3, P>0.05) and (15.84% (11.47%, 24.85%) vs. 16.95% (11.64%, 22.91%), P>0.05) in diabetic group. In non-diabetic group, the volume and percentage of LRNC were significantly decreased at 3 months (63.01 (44.25, 188.64) mm3 vs. 72.49 (51.91, 199.59) mm3, P<0.05) and (13.76% (8.81%, 27.64%) vs. 16.04% (11.18%, 27.05%), P<0.05) respectively. Both parameters further decreased to (55.63 (27.18, 179.40) mm3) and (12.71% (8.39%, 24.41%)) at 24 months (both P<0.05). Wall volume, lumen volume and percent wall volume (PWV) were not affected post therapy in both two groups(P>0.05). There were no correlations between the changes of plaque parameters including volume and percentage of LRNC, wall volume, lumen volume, PWV and the changes of blood lipid parameters (TC, LDL-C, HDL-C and TG) in 3 and 24 months (P>0.05). Conclusion: Lipid-lowering therapy possesses different effects on carotid atherosclerotic plaque in diabetic and non-diabetic patients, and the LRNC improvement is more significant in non-diabetic patients as compared to diabetic patients.

Analysis of cervical instability and clinical characteristics in treatment-naive rheumatoid arthritis patients / 北京大学学报(医学版)

OBJECTIVE@#To study the proportion of cervical spine instability in treatment-naive rheumatoid arthritis (RA) patients, to investigate the associated neck symptoms, and to analyze the clinical characteristics in treatment-naive RA patients and treated RA patients.@*METHODS@#RA patients who underwent cervical spine X-ray imaging from the Department of Rheumatology and Immunology of Peking University Third Hospital and Peking University Shenzhen Hospital from August 2015 to October 2019 and had clinical records of medication administration were included. Clinical and laboratory data including cervical symptoms and X-ray imaging data of cervical spine were collected. The constituent ratio of cervical spine instability in treatment-naive RA patients was statistically analyzed. The clinical data and laboratory data were analyzed by t-test, u-test and chi square to explore the clinical characteristics of the treatment-naive RA patients with cervical instability.@*RESULTS@#Of the 408 RA patients, 105 patients were treatment-naive. Of the 105 treatment-naive patients, 82.9% (87/105) were female, with an average age of (52±14) years, the median duration of the disease was 24 months, the shortest history was 2 weeks, and the longest history was 30 years. 28.6% (30/105) of the treatment-naive RA patients showed cervical spine instability. The prevalence of cervical instability was 13.6% in the treatment-naive RA patients with disease duration less than 24 months. Among them, there were no significant differences in neck symptoms between cervical spine instability group and none cervical spine instability group. The patients with cervical spine instability had a longer duration of disease [60 (18, 180) months vs.16 (8, 51) months], a higher proportion of peripheral joint deformity (63.3%vs.21.3%), and a lower hemoglobin [(106.90±21.61) g/L vs. (115.77±14.69) g/L]. There was no significant difference in the occurrence of cervical instability in the treatment-naive RA patients compared with treated RA patients. Among the RA patients with cervical instability, there was no statistically significant difference in the composition of each type between the patients with treatment-naive RA and patients with treated RA, except for a shorter duration of disease [120.0 (72.0, 240.0) months vs. 60.0 (27.0, 167.5) months].@*CONCLUSION@#28.6% of treatment-naive RA patients showed cervical spine instability. Cervical instability was also common in RA patients with a duration less than 24 months. There was no significant correlation between cervical instability and neck symptoms. Patients with cervical spine instability had a long-term disease, a higher proportion of peripheral joint deformity and a lower hemoglobin. Controlling the condition of RA early may help to control the progression of cervical involvement in patients with RA.

Application of tension-reducing distraction of external fixators for limb wound closure / 中华创伤杂志

Objective:To explore the effect of tension-reducing distraction of external fixators for limb wound closure.Methods:A retrospective case series study was made on data of 21 patients with refractory limb wounds admitted to 920th Hospital of Joint Logistics Support Force of PLA from January 2016 to July 2019. There were 15 males and 6 females，aged 11 to 56 years ［ （37.8 ± 11.2）years］. The lower-limb wounds were found in 15 patients and the upper-limb wound in 6 patients. The area of wound defect ranged from 1.2 cm × 1.0 cm to 22.0 cm × 17.1 cm. After debridement of the limb wound，the tension-reducing distraction of Ilizarov external fixators was used according to the shape and location of the wound. Distraction was applied at a rate of 1 mm/d starting at postoperative day 1 and the direction of distraction was adjusted according to the angle of skin closure of the trauma. The wound reduction distraction time and wound healing time were recorded. The wound healing score was used to evaluate wound healing at postoperative 5 days and 30 days. Complications were recorded according to the Paley classification. The wound survival curve was plotted to observe the time of wound tension reduction and traction and wound healing. The final wound healing was detected as well.Results:All patients were followed up for 3 to 9 months ［（4.5 ± 1.7）months］. The wounds were significantly reduced after reduction and distraction，with the reduction time of 6-23 days ［（7.8 ± 2.3）days］ and the wound healing time of 15-47 days ［（23.0 ± 3.3）days］. The wound healing score was （3.2 ± 0.9）points at postoperative 5 days and （0.7 ± 0.2）points at postoperative 30 days （ P < 0.05）. There were 15 problems，0 disorder，and 0 sequelae according to the Paley classification of complications. The wound survival curve showed the median time of reduction and distraction and wound healing was 16 days and 34 days，respectively. All patients showed wound healing without recurrence，of which 10 were healed directly，8 by implants and 3 by sutures. Conclusion:For patients with limb wounds difficult to be treated by flap coverage，the tension-reducing distraction of external fixators can effectively close the wound，fasten wound healing，shorten treatment period，and has fewer complications and a low recurrence rate.

Research advances on high-intensity interval training and cognitive function / 生理学报

High-intensity interval training (HIIT) has proven to be a time-saving and efficient exercise strategy. Compared with traditional aerobic exercise, it can provide similar or even better health benefits. In recent years, a number of studies have suggested that HIIT could be used as a potential exercise rehabilitation therapy to improve cognitive impairment caused by obesity, diabetes, stroke, dementia and other diseases. HIIT may be superior to regular aerobic exercise. This article reviews the recent research progress on HIIT with a focus on its beneficial effect on brain cognitive function and the underlying mechanisms. HIIT may become an effective exercise for the prevention and/or improvement of brain cognitive disorder.

Population distribution and clinical characteristics in rheumatoid arthritis patients with cervical spine instability / 北京大学学报(医学版)

OBJECTIVE@#To investigate the population distribution of cervical spine instability in rheumatoid arthritis (RA) patients, and to analyze the clinical characteristics in RA patients with cervical spine instability.@*METHODS@#A total of 439 RA patients who had completed cervical spine X-ray examination from Department of Rheumatology and Immunology of Peking University Shenzhen Hospital and Peking University Third Hospital from August 2015 to March 2019 were enrolled. The clinical data, laboratory data and cervical radiographic data were collected and analyzed by t-test, rank sum test and Chi-square test to clarify the clinical characteristics in the RA patients with cervical spine instability.@*RESULTS@#Of the 439 RA patients, 80.9% (355/439) were female, with an average age of (52.9±13.9) years, a median duration of the disease was 60 months, the shortest history was 2 weeks, and the longest history was up to 46 years. 29.6% (130/439) of the RA patients showed cervical spine instability. Among them, 20 RA patients were complicated with two different types of cervical instability, the atlantoaxial subluxation (AAS) accounted for 24.6% (108/439), the vertical subluxation (VS) accounted for 7.3% (32/439) and the subluxial subluxations (SAS) accounted for 2.3% (10/439). The patients with cervical spine instability had a longer duration of disease [120 (36, 240) months vs. 48 (12, 120) months], a higher proportion of peripheral joint deformity (56.9% vs. 29.9%), and a higher visual analog scale (VAS) measuring general health score (4.89±2.49 vs. 3.93±2.38), a lower hemoglobin [(111.31±19.44) g/L vs. (115.56±16.60) g/L] and a higher positive rate of anti-cyclic citrullina-ted peptide (CCP) antibody (90.8% vs. 76.6%). There were no significant differences in gender, age, number of swollen joints, number of tenderness joints, erythrocyte sedimentation rate, rheumatoid factor level, 28-joint disease activity score, positive rate of anti keratin antibody, duration of glucocorticoid use and duration of disease modifying anti-rheumatic drugs use between the two groups.@*CONCLUSION@#In the study, 29.6% of the RA patients showed cervical spine instability. RA patients with cervical spine instability had a long-term disease, a higher proportion of peripheral joint deformity, a higher VAS measuring general health score, a lower hemoglobin and a higher positive rate of anti-CCP antibody.

Embryo-fetal developmental toxicity and toxicokinetics of carenoprazan hydrochloride in rabbits / 中国药理学与毒理学杂志

OBJECTIVE To investigate the embryo-fetal developmental toxicity (EFDT) of careno?prazan hydrochloride (KFP-H008) in rabbits. METHODS Pregnant rabbits were given by gavage KFP-H008 at 5, 15 and 50 mg·kg-1 during the organogenetic period (gestation days 6-18, GD 6-18). Rabbits in positive control group were treated with cyclophosphamide (CP) 10 mg·kg-1 by iv. Maternal body mass and food consumption during gestation were recorded. Pregnant dams were euthanized on GD 29. The numbers of live/dead fetuses, resorptions, implantations, corpora lutea, and gravid uterus mass, placenta mass, fetal gender ratios, body mass, and skeletal development were evaluated. Moreover, the toxicokinetic parameters including AUC and C0-t, and tissue distributions were determined. RESULTS From GD 13, the maternal body mass and the food consumption in KFP-H00815 and 50 mg · kg-1 groups were lower than in the normal control group (P<0.05). Also, the reduced fetal crown rump length and mass, skeletal malformations/variations were observed in KFP-H00815 and 50 mg · kg-1 groups (P<0.05). KFP-H008 was rapidly eliminated, and became undetectable in the maternal plasma after a single administration. Following multiple KFP-H00850 mg · kg-1 treatment, both KFP-H008 and its metabolites were detectable in various tissues of the maternal and fetus, which might be the evidence for carenoprazan-induced developmental toxicity. In KFP-H00815 mg · kg-1 group, KFP-H008 and its metabolites were undetectable in most of maternal and fetal tissues. CONCLUSION The no observed adverse effect level (NOAEL) of KFP-H008 for maternal and fetal rabbits is about 5 mg·kg-1.

Advances in molecular pathogenesis and treatment of intrahepatic cholangiocarcinoma / 中华消化外科杂志

Intrahepatic cholangiocarcinoma (ICC) is a group of adenocarcinoma that derives from epithelium of the subbranches of intrahepatic bile ducts, which is characterized by difficulty in early diagnosis, high malignancy and poor prognosis. ICC is relatively rare, but it is the second most common in primary liver cancer, and its incidence has gradually increased worldwide. Radical resection is recognized as the only treatment that can bring better long-term survival currently. However, many surgery-related problems, such as lymph node dissection and major vascular resection and reconstruction, are still controversial. Adjuvant therapy, including chemotherapy, regional therapy, targeted therapy and immunotherapy, has received increasing attention in recent years. Although there is no uniform standard, a large number of related studies have supported its efficacy. In this article, the authors have reviewed the molecular pathogenesis of ICC and advances in treatment.

Development of Axial Resolution Testing Device for Optical Coherence Tomograph for the Posterior Segment of the Human Eye and Measurement Uncertainty Analysis / 中国医疗器械杂志

Based on the analysis of the theoretical calculation model of axial resolution of optical coherence tomograph for the posterior segment of the human eye, a set of testing device for measuring its axial resolution is designed and developed. In view of a commercial ophthalmic optical coherence tomograph in clinical use, its axial resolution is calculated to be 5.07 μm theoretically, and the actual measurement value is 5.45 μm. The uncertainty of the detection device is evaluated and the result is (5.45±0.10) μm. The measurement error introduced by the testing device is very small. Meanwhile, the axial resolution measured by the testing device meets the requirements of the instrument(≤ 6 μm).

Effect of sustained intensive therapy with disease modifying anti-rheumatic drugs in rheumatoid arthritis: a 5-year real-world consecutive study / 中华医学杂志(英文版)

BACKGROUND@#Intensive therapy with disease modifying anti-rheumatic drugs (DMARDs) has been reported to improve the outcomes of rheumatoid arthritis (RA). However, real-world study on the effect of intensive therapy on RA sustained remission is still lacking. This study aimed to investigate the outcome of sustained intensive DMARD therapy (SUIT) for RA in a real-world 5-year consecutive cohort.@*METHODS@#Based on a consecutive cohort of 610 out-patients with RA, remission of RA was assessed in 541 patients from 2012 to 2017, by dividing into SUIT, non-SUIT, and intermittent SUIT (Int-SUIT) groups. Changes in the disease activity scores were evaluated by 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR), 28-joint disease activity score based on C-reactive protein (DAS28-CRP), and clinical deep remission criteria (CliDR). Cumulative remission rates between different groups were compared using Kaplan-Meier curves and predictive factors of sustained remission were identified by univariate and multivariate logistic regression analysis.@*RESULTS@#The remission rates of the SUIT group decreased from 12.0% (65/541) to 5.6% (20/359) based on DAS28-ESR, from 14.0% (76/541) to 7.2% (26/359) based on DAS28-CRP, and from 8.5% (46/541) to 3.1% (11/359) based on CliDR, respectively, with a gradually decreasing trend during the 5 years. The SUIT regimen led to a significantly higher cumulative remission rate than non-SUIT regimen based on DAS28-ESR (39.7% vs. 19.5%, P = 0.001), DAS28-CRP (42.0% vs. 19.6%, P = 0.001), and CliDR (24.5% vs. 8.7%, P = 0.001). The cumulative remission rates of patients treated with SUIT regimen were significantly higher than those treated with Int-SUIT regimen based on DAS28-ESR (39.7% vs. 25.7%, P = 0.043) and CliDR (24.5% vs. 14.2%, P = 0.047), but there was no significant difference between the two groups based on DAS28-CRP (42.0% vs. 27.4%, P = 0.066). Multivariate logistic regression analysis showed that the use of SUIT regimen was an independent favorable predictor according to different remission definitions (for DAS28-ESR: odds ratio [OR], 2.215, 95% confidence interval [CI]: 1.271-3.861, P = 0.005; for DAS28-CRP: OR, 1.520, 95% CI: 1.345-1.783, P = 0.002; for CliDR: OR, 1.525, 95% CI: 1.314-1.875, P = 0.013).@*CONCLUSION@#Sustained intensive treatment of RA is an optimal strategy in daily practice and will lead to an increased remission rate.

Mechanism of effect of IL-17C on survival of kidney graft in mice / 器官移植

Objective To investigate the effect and mechanism of interleukin (IL)-17C in mice undergoing kidney transplantation. Methods The life-supporting kidney transplantation mice models were established using Balb/c (H-2Kd) mice as the donors, IL-17C gene knock out (IL-17CKO) mice (knockout group) and C57BL/6J(H-2Kb) mice (wild group) were chosen as the recipients. The postoperative body mass and survival time of mice were statistically compared between two groups. Pathological examination of the kidney graft was performed by using hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining. The expression levels of granzyme B, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-6 and IL-1β messenger ribonucleic acid (mRNA) in the kidney graft tissue were quantitatively measured by reverse transcription polymerase chain reaction (RT-PCR). The proportion of inflammatory cell infiltration in the kidney graft tissue was detected by flow cytometry. Results In the knockout group, the survival time of mice after kidney transplantation was significantly shorter than that of the wild mice (P=0.031). The body mass was more evidently decreased in the knockout group with no statistical significance from that in the wild group. Pathological examination demonstrated that the kidney graft injury in the knockout group was significantly worse than that in the wild group. The mRNA expression levels of granzyme B, IFN-γ, TNF-α, IL-6 mRNA in the knockout group were significantly up-regulated compared with those in the wild group (all P < 0.01). The mRNA expression level of IL-1β showed a decreasing trend with no statistical significance (P=0.16). Flow cytometry analysis revealed that the infiltration of CD45+CD11b+Ly6G+ neutrophil and CD45+CD11b+Ly6Chi monocyte in the kidney graft of knockout mice was significantly higher compared with that of the wild mice (P < 0.05, P < 0.01), whereas the infiltration of CD45+Ly6ChiF4/80+ macrophage did not significantly differ between two groups (P > 0.05). Conclusions IL-17C participates in the regulation of inflammatory response after kidney transplantation. It can alleviate acute rejection and improve the survival of kidney graft by down-regulating the expression of pro-inflammatory cytokines and infiltration of inflammatory cells.

Preliminary application of three dimensional printing surgical guide plate in orthognathic surgery for partial mandibular deformities / 中华医学美学美容杂志

Objective To evaluate the effectiveness of computer aided design (CAD) and three bit printing in the management of orthognathic surgery.Methods A total of 5 cases of patients with jaw deformity were involved in this study;jaw teeth and CT scanning laser scanning hefore surgery,virtual surgery design of 3D reconstruction and fusion data were analyzed,according to the design scheme of double jaw surgery combined with genioplasty;design and 3D printing of maxillary Le Fort Ⅰ osteotomy,genioplasty titanium alloy resin osteotomy and positioning guide,sagittal split ramus osteotomy by 3D printing and plate technology were used in this approach.The postoperative results were compared with the surgical planning by three-dimensional measurement and statistical analysis.Results When the operation guide plate was applied smoothly,the maximum error for maxilla was 1.2 mm (0.3-1.2 mm),and the maximum error for genioplasty was 1.7 mm,(0.5-1.7 mm),and the mean error was less than 1 mm.Follow-up for 12 months showed no adverse reaction.Conclusions Three dimensional printing surgical guide plate can accurately provide the osteotomy information,effectively control the jaw movement,and improve the orthognathic surgery accuracy of patients with partial jaw deformity.

Preliminary results of multicenter studies on ABO-incompatible kidney transplantation / 中华器官移植杂志

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.

Primary hepatic adenosquamous carcinoma: report of 5 cases / 中华普通外科杂志

Objective:To explore the clinicopathological characteristics of the primary hepatic adenosquamous carcinoma(ASC).Methods:A retrospective analysis was performed on the clinical data of 5 ASC patients admitted to the First Affiliated Hospital of Anhui Medical University from 2006 to 2019 who underwent surgical resection and were pathologically confirmed.Results:Among the 5 ASC cases, there were 4 males and 1 female. The age ranged from 48 to 73 years. As for the initial symptoms, there were 5 cases complaining upper abdominal pain, 2 cases presenting fever, 1 case presenting weight loss and 1 case presenting jaundice. CA19-9 was significantly higher than normal in 4 cases, while AFP was normal in all. None had definite preoperative diagnosis.All the 5 patients underwent surgical resection with pathology proved primary hepatic ASC. Lymph node metastasis was found in 4 cases and nerve invasion in 2 cases. There were 4 cases at TNM stage ⅣA, one at stage ⅠB. The median disease-free survival (DFS) was 5 months and the overall survival (OS) was 9 months.Conclusions:Primary hepatic adenosquamous carcinoma is a rare type of liver malignant tumor with an extremely poor prognosis. Surgical resection helps little in improving the prognosis.

Auxo action and mechanism of tgf-β1 up-regulating smad3 phosphorylation on the expression of thymic stromal lymphopoietin in human bronchial Epithelia / 解放军医学杂志

[Abstract] Objective To discuss the effect and the corresponding mechanism of transforming growth factor β1 (TGF-β1) in promoting the bronchial epithelia synthesis and the expression of thymic stromal lymphopoietin (TSLP), so seek out a potential therapeutic target for asthma. Methods Human bronchial epithelia cells (HBEc) were cultured in vitro, and then divided into 0h group, 3h group, 6h group, 12h group, 24h group and 48h group to evaluate the effect of TGF-β1 stimulation in different time points; and divided into 0ng/ml group, 0.1ng/ml group, 1ng/ml group and 10ng/ml group to evaluate the effect of TGF-β1 stimulation in different concentrations. SB431542, a TGF-β1 antagonist, was used to block the effect of TGF-β1, HBEc were divided into negative control group, TGF-β1 group (1ng/ml TGF-β1) and TGF-β1+SB431542 group (1ng/ml TGF-β1+10μmol/L SB431542). Western blotting was performed to detect the protein expression level of TSLP, p-Smad3 and Smad3, while qRT-PCR was performed to determine the mRNA transcription level of TSLP. Concentrations of TSLP in HBEc culture supernatants were measured by ELISA. Results As the co-culture time with TGF-β1 prolonged, the expression of TSLP in HBEc increased. The relative expression of TSLP protein was significantly higher in 24h group (0.803±0.022) than in 0h group (0.350±0.032, P<0.05), and the relative expression of TSLP mRNA also increased (4.957±0.391 vs. 1.002±0.086, P<0.05). The levels of TSLP mRNA transcription and protein expression were significantly higher in 1ng/ml TGF-β1 group (7.954±2.004; 1.522±0.003) than in 0ng/ml TGF-β1 group (1.008±0.152; 0.758±0.014, P<0.05). The concentrations of TSLP in HBEc culture supernatants were markedly higher in 1ng/ml TGF-β1 group than in 0ng/ml TGF-β1 group (160.157±7.050 vs. 138.817±1.940, P<0.05). The ratio of p-Smad3/Smad3 declined obviously in TGF-β1+SB431542 group than in TGF-β1 group (0.808±0.063 vs. 1.116±0.049, P<0.05). Meanwhile, the relative expression of TSLP protein was significantly lower in TGF-β1+SB431542 group than in TGF-β1 group (1.016±0.030 vs. 1.186±0.045, P<0.05). Conclusion TGF-β1 may induce the expression of TSLP in HBEc by up-regulating Smad3 phosphorylation, which may be a novel method in curing asthma.

Clinical deep remission and related factors in a large cohort of patients with rheumatoid arthritis / 中华医学杂志(英文版)

Background:@#Clinical remission is the treatment target in rheumatoid arthritis (RA). This study aimed to investigate clinical remission and related factors in a large cohort of patients with RA.@*Methods:@#This study composed of 342 patients with RA. Data were collected by face-to-face interview of 1049 patients with RA who visited the Department of Rheumatology of three teaching hospitals from September 2015 to May 2016. The patients with RA were clinically assessed by rheumatologists and a four-page questionnaire was completed on site. Subsequently, patients fulfilled remission criteria were further analyzed. The practicability of different definitions of remission of RA was rated by a panel of rheumatologists. Sustained intensive disease modifying anti-rheumatic drug (DMARD) treatment was defined as a combination treatment with two or more DMARDs for at least 6 months.@*Results:@#In this cohort of 342 patients with RA, the proportions of patients achieving remission were 38.0%, 29.5%, 24.9%, 21.1%, 19.0%, 18.1%, and 17.0%, based on criteria of disease activity score in 28 joints (DAS28) using CRP (DAS28-CRP), DAS28 using ESR (DAS28-ESR), routine assessment of patient index data 3 (RAPID-3), Boolean, simplified disease activity index (SDAI), clinical disease activity index, and the newly described clinical deep remission (CliDR), respectively. Boolean and CliDR are the best in practicability scored by rheumatologists (7.5 and 8.0, respectively). Compared with the non-sustained intensive group, sustained intensive treatment with DMARDs yielded higher remission rates of 25.6%, 23.8%, and 21.3% in patients with RA based on Boolean (χ2=3.937, P=0.047), SDAI (χ2=4.666, P=0.031), and CliDR criteria (χ2=4.297, P=0.038). The most commonly prescribed conventional synthesized DMARDs (csDMARDs) in patients with RA was leflunomide, followed by methotrexate, and hydroxychloroquine. Compared with the non-remission group, patients achieving remission had a longer median duration of DMARDs (45.0 [22.8–72.3] months, Z=-2.295, P=0.022).@*Conclusions:@#The findings in this study indicated that clinical deep remission is achievable in patients with RA. Sustained intensive DMARD treatment is needed to achieve a better outcome in RA.

Early postoperative complications and risk factors in laparoscopic D2 radical gastrectomy for gastric cancer / 中华胃肠外科杂志

Objective@#To investigate the morbidity and treatment of early postoperative complications after laparoscopic D2 radical gastrectomy for gastric cancer, and to explore the risk factors.@*Methods@#A case-control study was performed to retrospectively collect clinicopathological data of 764 patients undergoing laparoscopic D2 radical gastrectomy for gastric cancer at our department between January 2015 and December 2017. Patient inclusion criteria: (1) gastric cancer diagnosed by preoperative electronic gastroscopy and biopsy, and confirmed by postoperative pathology; (2) without invasion into adjacent organs by preoperative evaluation of tumors; (3) tumors without definite liver and distant metastasis; (4) R0 resection of gastric cancer and standard D2 lymph node dissection; (5) patients with informed consent. Exclusion criteria: (1) unperformed laparoscopic D2 radical resection; (2) other types of gastric tumor confirmed by pathology; (3) cases with incomplete clinical data. Complication occurring within two weeks after laparoscopic D2 gastrectomy was defined as early postoperative complication. Patients were divided into two groups: non-complication group (693 cases) and complication group (71 cases) according to the occurrence of complications after operation. The clinicopathological data of two groups were analyzed and compared with t test and χ2 test, and the factors of P < 0.2 were included in the multivariate logistic regression model to analyze the risk factors of postoperative complications.@*Results@#Of 764 patients, 71 (9.3%) developed early postoperative complications, with median onset time of 3 (1 to 11) days. Surgical complications accounted for 7.9% (60/764), including 13 cases (1.7%) of abdominal hemorrhage, 12 cases (1.6%) of anastomotic leakage, 10 cases (1.3%) of incision infection, 8 cases (1.0%) of anastomotic bleeding, 7 cases (0.9%) of gastric stump weakness, 4 cases (0.5%) of abdominal infection, 4 cases (0.5%) of duodenal stump leakage and 2 cases (0.3%) of small intestinal obstruction. Non-surgical complications accounted for 1.4% (11/764), including 6 cases (0.8%) of pulmonary infection and 5 cases (0.7%) of cardiovascular disease. Two cases (0.3%) died of sepsis caused by severe abdominal infection; 9 cases (1.2%) recovered after receiving the second operation, among whom 5 cases were abdominal hemorrhage, 2 cases were anastomotic leakage and 2 cases were duodenal stump leakage; the remaining patients were healed with conservative treatment. Compared with patients without complications, patients with complications had higher proportions of BMI ≥24 kg/m2 [42.3% (30/71) vs. 24.2%(168/693), χ2=10.881, P=0.001], comorbity [64.8% (46/71) vs. 33.5% (232/693), χ2=27.277, P<0.001], combined organ resection [70.4% (50/71) vs. 20.5% (142/693), χ2=85.338, P<0.001], and pTNM stage of III [70.4% (50/71) vs. 40.1% (278/693), χ2=24.196, P<0.001], meanwhile had longer time to postoperative flatus [(4.2±2.1) days vs. (2.9±1.2) days, t=4.621, P=0.023], longer hospital stay [(34.6±12.6) days vs. (14.2±6.2) days, t=9.862, P<0.001] and higher hospitalization cost [(126.8±64.5) thousand yuan vs. (85.2±35.8) thousand yuan, t=11.235, P<0.001]. Multivariate analysis showed that BMI ≥24 kg/m2 (OR=3.762, 95% CI: 1.960-8.783, P=0.035), accompanying disease (OR=8.620, 95% CI: 1.862-29.752, P<0.001), combined organ resection (OR=6.210, 95% CI: 1.357-21.568, P=0.026), and pTNM stage (OR=4.752, 95% CI: 1.214-12.658, P<0.001) were the independent risk factors of postoperative complications.@*Conclusions@#Laparoscopic D2 radical gastrectomy is a safe and effective approach for gastric cancer. Most early postoperative complications can obtain satisfactory efficacy after conservative treatment. Perioperative management should be strengthened for those patients with high BMI, accompanying diseases, combined organ resection, and advanced pTNM stage.