Analysis of clinicopathological characteristics, therapeutic strategy and prognosis of 501 patients with gastric neuroendocrine neoplasms attending a single center / 中华胃肠外科杂志

Objective: To explore the clinicopathological features, treatment strategy and to analysis of prognosis-related risk factors of gastric neuroendocrine neoplasms(G-NEN). Methods: In this study, a retrospective observational study method was used to collect the clinicopathological data of patients diagnosed with G-NEN by pathological examination in the First Medical Center of PLA General Hospital from January 2000 to December 2021. The basic information of the patients, tumor pathological characteristics, and treatment methods were entered, and the treatment information and survival data after discharge were followed up and recorded. The Kaplan-Meier method was used to construct survival curves, and the log-rank test to analyze the differences in survival between groups. Cox Regression model analysis of risk factors affecting the prognosis of G-NEN patients. Results: Among the 501 cases confirmed as G-NEN, 355 were male and 146 were female, and their median age was 59 years. The cohort comprised 130 patients (25.9%) of neuroendocrine tumor (NET) G1, 54 (10.8%) of NET G2, 225 (42.9%) of neuroendocrine carcinoma (NEC), and 102 cases (20.4%) of mixed neuroendocrine-non-neuroendocrine(MiNEN). Patients NET G1 and NET G2 were mainly treated by endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR). The main treatment for patients with NEC/MiNEN was the same as that for gastric malignancies, namely radical gastrectomy+lymph node dissection supplemented with postoperative chemotherapy. There were significant differences in sex, age, maximum tumor diameter, tumor morphology, tumor numbers, tumor location, depth of invasion, lymph node metastasis, distant metastasis, TNM staging and expression of immunohistological markers Syn and CgA among NET, NEC, and MiNEN patients (all P<0.05). Further for NET subgroup analysis, there were significant differences between NET G1 and NET G2 in the maximum tumor diameter, tumor shape and depth of invasion(all P<0.05). 490 patients (490/501, 97.8%) were followed up with a median of 31.2 months. 163 patients had a death during follow-up (NET G1 2, NET G2 1, NEC 114, MiNEN 46). For NET G1, NET G2, NEC and MiNEN patients,the 1-year overall survival rates were 100%, 100%, 80.1% and 86.2%, respectively; the 3-year survival rates were 98.9%, 100%, 43.5% and 55.1%, respectively. The differences were statistically significant (P<0.001). Univariate analysis showed that gender, age, smoking history, alcohol history, tumor pathological grade, tumor morphology, tumor location, tumor size, lymph node metastasis, distant metastasis, and TNM stage were associated with the prognosis of G-NEN patients (all P<0.05). Multivariate analysis showed that age ≥60 years, pathological grade of NEC and MiNEN, distant metastasis, and TNM stage III-IV were independent factors influencing the survival of G-NEN patients (all P<0.05). 63 cases were stage IV at initial diagnosis. 32 of these were treated with surgery and 31 with palliative chemotherapy. Stage IV subgroup analysis showed that the 1-year survival rates were 68.1% and 46.2% in the surgical treatment and palliative chemotherapy groups, respectively, and the 3-year survival rates were 20.9% and 10.3%, respectively; the differences were statistically significant (P=0.016). Conclusions: G-NEN is a heterogeneous group of tumors. Different pathological grades of G-NEN have different clinicopathological features and prognosis. Factors such as age ≥ 60 years old, pathological grade of NEC/MiNEN, distant metastasis, stage III, IV mostly indicate poor prognosis of patients. Therefore, we should improve the ability of early diagnosis and treatment, and pay more attention to patients with advanced age and NEC/MiNEN. Although this study concluded that surgery improves the prognosis of advanced patients more than palliative chemotherapy, the value of surgical treatment for patients with stage IV G-NEN remains controversial.

Melatonin Attenuates Mitochondrial Damage in Aristolochic AcidInduced Acute Kidney Injury

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN).AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

Multicenter epidemiological characteristics of Mycoplasma pneumoniae infection in children in Hainan Province, 2012-2020 / 中国热带医学

@#Abstract: Objective　To analyze the epidemiological characteristics (season, age, gender, mixed infection and clinical manifestations, etc.) of Mycoplasma pneumoniae (MP) infection in children in Hainan Province, so as to provide epidemiological evidence-based medical basis for the prevention and control of MP infection in children in Hainan Province. Methods　The serum IgM antibodies of MP, Legionella pneumophila, Chlamydia pneumoniae, adenovirus, respiratory syncytial virus (RSV), Q fever Rickettsia, parainfluenza virus, influenza A virus and influenza B virus in children with respiratory tract infections (RTIs) who were hospitalized in pediatrics of many hospitals in Hainan Province from March 2012 to February 2020 were detected by indirect immunofluorescence method. The positive serum MP-IgM antibody was defined as MP infection. The epidemiological and clinical data of MP infected cases were analyzed retrospectively. Results　From March, 2012 to February, 2020, a total of 35 731 qualified pediatric inpatients with RTIs in many hospitals in Hainan Province were tested for serum MP-IgM with the total positive rate of 39.12% (13 978/35 731). The yearly positive rates of MP-IgM from 2012 to 2020 were 48.39%, 56.23%, 56.62%, 47.04%, 29.71%, 24.14%, 47.55%, 36.84% and 24.46% respectively. The positive rates of MP-IgM in 2013 and 2014 were significantly higher than those in other years (P<0.05). The positive rate of MP-IgM in summer in Hainan Province was the highest (41.34%) and the lowest in winter (35.77%) (P<0.05). MP infection occurred in all age groups, the positive rate of MP-IgM in children of preschool (51.80%) was significantly higher than that in other age groups (P<0.01), and the positive rate of MP IgM in children of infancy (15.36%) was lower than that in other age groups (P<0.01). The positive rate of MP-IgM in female was 44.77%, which was significantly higher than that in male (35.83%) (P<0.05). MP infection combined with positive IgM of another pathogen accounted for 32.63% (4 561 cases), positive IgM of another two pathogens accounted for 1.26% (176 cases). MP infection was mostly found in pneumonia (68.73%), and the main clinical symptoms were cough (84.72%), fever (51.01%) and wheezing (3.16%). Conclusions　MP is an important pathogen of respiratory tract infection in children in Hainan Province, and infection is more common in children in early school age and early childhood. Mp-specific tests should be performed to identify the pathogen in children suspected of MP infection. In the high incidence season, health education should be strengthened in kindergartens, schools and other places to prevent respiratory tract infection.

Research progress on cold ischemia injury of steatotic donor livers / 器官移植

Liver transplantation is a vital treatment for end-stage liver disease. However, the shortage of donor livers has limited the development of liver transplantation. How to expand the source of donor livers has become a challenge in the academic community. In recent years, the proportion of donors with non-alcoholic fatty liver disease (NAFLD) has been increased. Rational use of steatotic donor livers is a feasible approach to expand the donor pool. Cold ischemia injury during donor liver preservation before liver transplantation increases the risk of postoperative organ dysfunction. Therefore, it is of significance to unravel the mechanism and intervention measures of cold ischemia injury of steatotic donor livers. Cold ischemia injury of steatotic donor livers is characterized as the damage of mitochondria, lysosomes and endoplasmic reticulum at the organelle level, and up-regulated expression of adenosine monphosphate activated protein kinase (AMPK), aldehyde dehydrogenase 2 (ALDH2) and heme oxygenase (HO)-1 at the protein level. In this article, the research progresses on cold ischemia injury of steatotic donor livers and relevant intervention measures were reviewed.

Establishment and validation of a nomogram for predicting prognosis of gastric neuroendocrine neoplasms based on data from 490 cases in a single center / 南方医科大学学报

OBJECTIVE@#To develop and validate a nomogram for predicting outcomes of patients with gastric neuroendocrine neoplasms (G-NENs).@*METHODS@#We retrospectively collected the clinical data from 490 patients with the diagnosis of G-NEN at our medical center from 2000 to 2021. Log-rank test was used to analyze the overall survival (OS) of the patients. The independent risk factors affecting the prognosis of G-NEN were identified by Cox regression analysis to construct the prognostic nomogram, whose performance was evaluated using the C-index, receiver-operating characteristic (ROC) curve, area under the ROC curve (AUC), calibration curve, DCA, and AUDC.@*RESULTS@#Among the 490 G-NEN patients (mean age of 58.6±10.92 years, including 346 male and 144 female patients), 130 (26.5%) had NET G1, 54 (11.0%) had NET G2, 206 (42.0%) had NEC, and 100 (20.5%) had MiNEN. None of the patients had NET G3. The numbers of patients in stage Ⅰ-Ⅳ were 222 (45.3%), 75 (15.3%), 130 (26.5%), and 63 (12.9%), respectively. Univariate and multivariate analyses identified age, pathological grade, tumor location, depth of invasion, lymph node metastasis, distant metastasis, and F-NLR as independent risk factors affecting the survival of the patients (P < 0.05). The C-index of the prognostic nomogram was 0.829 (95% CI: 0.800-0.858), and its AUC for predicting 1-, 3- and 5-year OS were 0.883, 0.895 and 0.944, respectively. The calibration curve confirmed a good consistency between the model prediction results and the actual observations. For predicting 1-year, 3-year and 5-year OS, the TNM staging system and the nomogram had AUC of 0.033 vs 0.0218, 0.191 vs 0.148, and 0.248 vs 0.197, respectively, suggesting higher net benefit and better clinical utility of the nomogram.@*CONCLUSION@#The prognostic nomogram established in this study has good predictive performance and clinical value to facilitate prognostic evaluation of individual patients with G-NEN.

Preliminary experience with double-tract reconstruction combined with π-shaped esophagojejunal anastomosis after total laparoscopic proximal gastrectomy for the treatment of adenocarcinoma of esophagogastric junction / 中华胃肠外科杂志

Objective: To explore the feasibility and preliminary technical experience of the double-tract reconstruction combined with π-shaped esophagojejunal anastomosis after total laparoscopic proximal gastrectomy (TLPG) in the treatment of adenocarcinoma of esophagogastric junction (AEG). Methods: A descriptive case series study method was used. Clinical data of 12 AEG patients who underwent the double-tract reconstruction combined with π-shaped esophagojejunal anastomosis after TLPG from January 2021 to June 2021 at the Department of General Surgery, First Medical Center, PLA General Hospital were retrospectively analyzed. Among the 12 patients, the median tumor diameter was 2.0 (1.5-2.9) cm, and the pathological stage was T1-3N0-3aM0. All the patients routinely underwent TLPG and D2 lymph node dissection with double-tract reconstruction combined with π-shaped esophagojejunal anastomosis: (1) Double-tract reconstruction combined with π-shaped esophagojejunal anastomosis: mesentery 25 cm away from the Trevor ligament was treated, and an incision of about 1 cm was made on the mesenteric border of the intestinal wall and the right wall of the esophagus, two arms of the linear cutting closure were inserted, and esophagojejunal side-to-side anastomosis was performed. A linear stapler was used to cut off the lower edge of the anastomosis and close the common opening to complete the esophagojejunal π-shaped anastomosis. (2) Side-to-side gastrojejunostomy anastomosis: an incision of about 1 cm was made at the jejunum to mesenteric border and at the greater curvature of the remnant stomach 15 cm from the esophagojejunostomy, and a linear stapler was inserted to complete the gastrojejunostomy side-to-side anastomosis. (3) Side-to-side jejunojejunal anastomosis: an incision of about 1 cm was made at the proximal and distal jejunum to the mesangial border 40 cm from the esophagojejunostomy, and two arms of the linear stapler were inserted respectively to complete the side-to-side jejunojejunal anastomosis. A midline incision about 4-6 cm in the upper abdomen was conducted to take out the specimen, and an abdominal drainage tube was placed, then layer-by-layer abdominal closure was performed.@*INDICATIONS@#(1) adenocarcinoma of esophagogastric junction (Seiwert type II-III) was diagnosed by endoscopy and pathological examination; (2) ability to preserve at least 1/2 of the distal stomach after R0 resection of proximal stomach was evaluated preoperatively.@*CONTRAINDICATIONS@#(1) evaluation indicated distant metastasis of tumor or invasion of other organs; (2) short abdominal esophagus or existence of diaphragmatic hiatal hernia was assessed during the operation; (3) mesentery was too short or the tension was too high; (4) existence of severe comorbidities before surgery; (5) only palliative surgery was required in preoperative evaluation; (6) poor nutritional status.@*MAIN OUTCOME MEASURES@#operation time, intraoperative blood loss, postoperative complications, time to first flatus and time to start liquid diet, postoperative hospital stay, operation cost, etc. Continuous variables that conformed to normal distribution were presented as mean ± standard deviation, and those that did not conform to normal distribution were presented as median (Q1,Q3). Results: All the patients successfully completed TLPG with double-tract reconstruction combined with π-shaped esophagojejunal anastomosis, and postoperative pathology showed that no cancer cells were found on the upper incision margin. The operation time was (247.9±62.4) minutes, the median intraoperative blood loss was 100.0 (62.5, 100.0) ml, no intraoperative blood transfusion was required, the incision length was (4.9±1.0) cm, and the operation cost was (55.5±0.7) thousand yuan. The median time to start liquid diet was 1.0 (1.0, 2.0) days, and the mean time to flatus was (3.1±0.9) days. All the patients were discharged uneventfully. Only 1 patient developed postoperative paralytic ileus and infectious pneumonia with Clavien-Dindo classification of grade II. The patient recovered after conservative treatment. There was no surgery-related death. The postoperative hospital stay was (8.3±2.1) days. Conclusion: The double-tract reconstruction combined with π-shaped esophagojejunal anastomosis after TLPG is safe and feasible, which can minimize surgical trauma and accelerate postoperative recovery.

A comparative study on short-term outcomes and quality of life for gastric cancer patients between totally laparoscopic total gastrectomy using an endoscopic linear stapler and laparoscopic-assisted total gastrectomy using a circular stapler / 中华胃肠外科杂志

Objective: To explore the differences of short-term outcomes and quality of life (QoL) for gastric cancer patients between totally laparoscopic total gastrectomy using an endoscopic linear stapler and laparoscopic-assisted total gastrectomy using a circular stapler. Methods: A retrospective cohort study was conducted. Clinicopathological data of patients with stage I to III gastric adenocarcinoma who underwent laparoscopic total gastrectomy from January 2017 to January 2020 were retrospectively collected. Those who were ≥80 years old, had serious complications that could affect the quality of life, underwent multi-organ resections, palliative surgery, emergency surgery due to gastrointestinal perforation, obstruction, bleeding, died or lost to follow-up within 1 year after surgery were excluded. A total of 130 patients were enrolled and divided into circular stapler group (CS group, 77 cases) and linear stapler group (LS group, 53 cases) according to the surgical method. The differences of age, gender, body mass index, number of comorbidities, history of abdominal surgery, ASA, tumor location, degree of differentiation, tumor length, tumor T stage, tumor N stage, tumor pathological stage and preoperative quality of life between the two groups were not statistically significant (all P>0.05). The observation indicators: (1) Surgery and postoperative conditions. (2) Postoperative complications: Any adverse conditions that require conservative treatment or surgical intervention after surgery were defined as postoperative complications, of which, complications occurring within 30 days after surgery were defined as early complications; complications occurring within 30 days to 1 year after surgery were defined as late complications. (3) Postoperative quality of life was assessed by the quality of life core scale (QLQ-C30) and gastric cancer specific module scale (QLQ-STO22). The higher the scores of functional scales and global health status, the better the corresponding quality of life. The higher the scores of symptoms scales, the worse the corresponding quality of life. Results: (1) Surgery and postoperative conditions: Compared with the CS group, the LS group presented less intraoperative blood loss [50.0 (50.0-100.0) ml vs. 100.0 (100.0-100.0) ml, Z=-3.111, P=0.002] and earlier time to flatus [(3.1±0.8) days vs. (3.5±1.1) days, t=-2.490, P=0.014]. However, there were no statistically significant differences between two groups of patients in terms of operation time, time to start a liquid diet and postoperative hospital stay (all P>0.05). (2) Postoperative complications: The early complication rates of the CS group and the LS group were 22.1% (17/77) and 18.9% (10/53), respectively, while the late complication rate were 18.2% (14/77) and 15.1% (8/53), respectively, whose differences were not statistically significant (all P>0.05). (3) Postoperative quality of life: After 1-year follow-up, 7 (5.4%) patients were lost, including 5 in CS group and 2 in LS group. One year after operation, the QLQ-C30 scale showed that the score of financial difficulty of the LS group was significantly higher than that of the CS group [33.3 (0 to 33.3) vs.0 (0 to 33.3), Z=-1.972, P=0.049] with statistically significant difference, and there were no statistically significant differences in the scores of other functional fields and symptom fields between the two groups (all P>0.05). The QLQ-STO22 scale showed that the scores of dysphagia [0 (0 to 5.6) vs. 0 (0 to 11.1), Z=-2.094, P=0.036] and eating restriction were significantly lower [0 (0 to 4.2) vs. 0 (0 to 8.3), Z=-2.011, P=0.044] in patients of the LS group than those of the CS group. There were no significant differences in scores of other symptoms between two groups (all P>0.05). Conclusions: Compared with the circular stapler, the esophagojejunostomy with linear stapler for gastric cancer patients can reduce intraoperative blood loss, shorten the time to flatus after operation, alleviate the symptoms of dysphagia and eating restriction but increase the economic burden to a certain degree.

Risk factors of postoperative complication after total gastrectomy in advanced gastric cancer patients receiving neoadjuvant chemotherapy / 中华胃肠外科杂志

Objective: At present, there are few studies focusing on the factors short-term complications after total gastrectomy in patients with advanced gastric cancer receiving neoadjuvant chemotherapy (NACT). The purpose of this study is to provide a reference for clinical prevention of complications in these patients. Methods: A retrospective case-control study was conducted. Case inclusion criteria: (1) clinical stage II-III gastric cancer diagnosed by preoperative gastroscopy, pathology, abdominal CT, EUS or PET-CT; (2) evaluated suitable for NACT by MDT discussion; (3) no previous history of other malignant tumors and no concurrent tumor; (4) undergoing total gastrectomy+ D2 lymphadenectomy after NACT. Exclusion criteria: (1) age <18 or >80 years old; (2) severe concurrent diseases, and ASA classification>grade III; (3) stump gastric cancer or history of gastric surgery; (4) incomplete clinicopathological data. According to the above criteria, clinicopathological data of 140 advanced gastric cancer patients who underwent total gastrectomy after NACT in Chinese PLA General Hospital between June 2012 and June 2019 were collected, including 109 males and 31 females with mean age of (56.9±11.4) years and body mass indey (BMI) of (23.3±3.1) kg/m(2). Logistic analysis was used to analyze the relationship between postoperative complication and clinicopathological data. Factors in univariate analysis with P<0.05 were included in the multivariate analysis. Results: Postoperative complications (Clavien-Dindo classification ≥ II) occurred in 35 cases (25.0%) and severe complications (Clavien-Dindo classification ≥ IIIa) occurred in 4 cases (2.9%), including 1 case of esophago-jejunal anastomotic leakage, 1 case of vena cava thrombosis, 1 case of pleural effusion, 1 case of septic shock during perioperative days resulting in death. Univariate analysis showed that BMI (P=0.011), cycle of NACT (P=0.027), tumor diameter (P=0.021), and vascular invasion (P=0.033) were associated with postoperative complication within 30 days, while open/laparoscopic total gastrectomy were not associated with postoperative complication (P=0.926). Multivariate analysis revealed that BMI ≥ 25 kg/m(2) (OR=3.294, 95% CI: 1.343-8.079, P=0.009) and < 4 cycles of NACT (OR=2.922, 95% CI: 1.217-7.016, P=0.016) were independent risk factors for postoperative complication. The 3-year overall survival rates of patients with or without complication were 54.4% and 64.0%, respectively (P=0.395), and 3-year disease-free survival rates were 47.4% and 52.9%, respectively (P=0.587). Conclusions: Higher BMI and fewer cycles of NACT are independent risk factors of postoperative complication in advanced gastric cancer patients undergoing total gastrectomy after NACT. No obvious association is found between postoperative complication and surgical approaches.

Effect of heavy metal lead on anticoagulant activity of leech based on label-free quantitative proteomics / 中国中药杂志

Whitmania pigra is the most widely distributed species of leeches in the market. In this study, the effect of heavy metal lead pollution on the anticoagulant activity of Wh. pigra was studied and the potential mechanism was explored. Pb(NO_3)_2 was used to contaminate the breeding soil which was then used to rear Wh. pigra for 50 days(lead-contaminated group, LC group), and meanwhile the blank control group(CG group) was set. Proteins were extracted from the obtained leech samples, and the differentially expressed proteins between LC and CG groups were analyzed by label-free proteomics technology. In this study, a total of 152 differentially expressed proteins were screened out, of which 93 proteins were up-regulated and 59 proteins were down-regulated in LC group. Bioinformatics analysis showed that the biological processes enriched with the differentially expressed proteins were mainly vesicle-mediated transport and transport positive regulation; the enriched cell components were mainly endocytosis vesicles and apical plasma membrane; the enriched molecular functions mainly included carbohydrate binding. The differentially expressed proteins were enriched in 76 KEGG pathways, which mainly involved metabolic pathways, biosynthesis of secondary metabolites, and bacterial invasion of epithelial cells. In this study, two differentially expressed proteins with Antistasin domain were presumed, which provides reference for further exploring the regulatory mechanism and signal transduction underlying the effect of lead pollution on the anticoagulant activity of leech.

Determination of caffeine content in Ginkgo Folium by ultra high performance liquid chromatography-triple quadrupole mass spectrometry / 中国中药杂志

In this experiment, an ultra-high performance liquid chromatographytandem triple quadrupole mass spectrometry was established for the determination of caffeine in commercially available Ginkgo Folium. The samples were extracted by ultrasonic method with methanol, and separated on Waters CORTECS T3 column(2.1 mm×100 mm, 2.7 μm), with mobile phase of 0.1% formic acid solution-0.1% formic acid acetonitrile solution for gradient elution, at flow rate of 0.3 mL·min~(-1); column temperature of 30 ℃, and injection volume of 2 μL. Mass spectrometry was conducted at ESI~+ multiple reaction monitoring(MRM) mode; quantitative analysis was conducted with external standard method. The results showed that in the range of 0.099 6-9.96 ng·mL~(-1), there was a good linear relationship between the mass concentration of caffeine and the peak area, R~2=0.999; the average recovery was 84.51%, with RSD of 6.2%. The results of precision, repeatability and stability showed that the RSD was 5.1%, 5.9%, 7.2%, respectively. The content range of caffeine in 10 batches of Ginkgo Folium was 1.52-60.86 μg·kg~(-1). In conclusion, this method is accurate, reliable and reproducible, which provides a reference for the safety study of Ginkgo Folium.

Advance in Flexible Variable Stiffness Actuator of Rehabilitation Robot (review) / 中国康复理论与实践

Flexible variable stiffness actuator is divided into four categories including elastic element, pneumatic element, electric-magnetic element and intelligent material. It is gradually applied in rehabilitation robot. It could adapt the change of patient's impedance in the upper and lower limb rehabilitation robots, ensure the safety of the wearer in the exoskeleton, and improve the biomimetics in the prosthesis. Variable stiffness driving mechanism for rehabilitation robot still has some disadvantages. It is proposed to have compact structure, low power consumption, good stiffness characteristics, high response rate and progressive output torque curve, etc.

Progress on biomarkers of EB virus-related posttransplant lymphoproliferative disease / 器官移植

Posttransplant lymphoproliferative disease (PTLD) is a series of heterogeneous lymphoproliferative diseases and a severe complication after solid organ transplantation in children. Over 70% of PTLD is associated with Epstein-Barr virus (EBV). EBV-related B-cell lymphoma is also the main malignant tumor after pediatric organ transplantation. EBV-related PTLD is still a challenge in pediatric solid organ transplantation, which is mainly caused by immune function damage induced by immune suppression after transplantation. However, the specific mechanism remains elusive. In recent years, biomarkers have been developed to guide the diagnosis and individualized treatment of EBV-related PTLD, which possesses excellent application prospect. In this article, research progresses on the incidence of EBV-related PTLD in solid organ transplantation and its biomarkers were reviewed, aiming to explore novel ideas for clinical diagnosis and treatment.

A pyrene-based ratiometric fluorescent probe with a large Stokes shift for selective detection of hydrogen peroxide in living cells / 药物分析学报

Hydrogen peroxide (H2O2) plays a significant role in regulating a variety of biological processes. Dys-regulation of H2O2 can lead to various diseases. Although numerous fluorescent imaging probes for H2O2 have been reported, the development of H2O2 ratiometric fluorescent probe with large Stokes shift re-mains rather limited. Such probes have shown distinct advantages, such as minimized interference from environment and improved signal-to noise ratio. In this work, we reported a new pyrene-based com-pound Py-VPB as H2O2 fluorescent probe in vitro. The probe demonstrated ratiometric detection behavior, large Stokes shift and large emission shift. In addition, the probe showed high sensitivity and selectivity towards H2O2 in vitro. Based on these excellent properties, we successfully applied Py-VPB to the visualization of exogenous and endogenous H2O2 in living cells. Cell imaging study also showed that our probe was localized in the mitochondria. We envision that the probe can provide a useful tool for unmasking the biological roles of mitochondrial H2O2 in living systems.

Analysis on Gene Set Enrichment of Related Signaling Pathways and Immune Infiltration in Intracranial Aneurysm / 中国实验方剂学杂志

Objective::Based on gene array technology, gene set enrichment analysis (GSEA) and immune infiltration analysis were performed on chip data of intracranial aneurysm (IA) mRNA expression profile, in order to provide theoretical basis for understanding the formation mechanism of IA. Method::The GSE75436 raw data were obtained from the gene expression omnibus (GEO). GSEA of biological process (BP) in gene ontology (GO) and Kyoto gene and genome encyclopedia (KEGG) signaling pathways were analyzed for gene expression profile by R software. The CIBERSORT deconvolution method was used to analyze the infiltration ratio of 22 types of immune cells in the expression profile. And COREMINE database was used to predict traditional Chinese medicines (TCMs), which were significant correlation with the enrichment result. Result::The GSEA results showed that the changes in gene expression of IA samples mainly involved in the regulation of cytokines, activation and differentiation of leukocyte, inflammatory immune response and other processes. The infiltration matrix analysis of immune cells showed that mast cells resting and neutrophils were significantly reduced in IA samples. The comparison of paired samples showed that mast cells and natural killer cells (NK cells) were significantly activated in the IA samples of the same individual, while neutrophils and T cells CD4 naive were significantly reduced. Through COREMINE prediction, it was found that Stephaniae Tetrandrae Radix was correlated with the activation of granulocytes, Sapindi Mukorossi Semen and Pistaciae Chinensis Cortex were correlated with the activation of neutrophils, Trichosanthis Semen, Paeoniae Radix Alba and Ligustri Lucidi Fructus were correlated with the cytotoxicity mediated by NK cells. Conclusion::Activation of mast cells and NK cells are closely associated with the occurrence and development of IA. The inflammatory immune processes and pathways such as nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) signaling pathway and cytotoxicity mediated by NK cells may be important factors in the pathogenesis of IA, and TCMs such as Stephaniae Tetrandrae Radix may be the potential molecular drug sources.

CO Laser Moxibustion for Knee Osteoarthritis: Study Protocol for A Multicenter, Double-blind, Randomized Controlled Trial / 中国结合医学杂志

BACKGROUND@#Knee osteoarthritis (OA) is a major cause of disability among the older adults. Few treatments are safe and effective. Moxibustion is commonly used in treating knee OA in Chinese medicine (CM). CO Laser moxibustion device is a substitute for traditional moxibustion, which mimics the effects of traditional moxibustion. More data are needed to support its application in knee OA.@*OBJECTIVE@#ObjectiveThe trial aims to assess the effect and safety of CO laser moxibustion in patients with knee osteoarthritis compared with a sham control.@*METHODS@#This is a protocol for a multicenter, randomized, double-blind, placebo-controlled trial. A total of 392 participants were recruited and assigned to the CO laser moxibustion group and sham laser moxibustion group with a 1:1 ratio at 6 outpatient clinics in Shanghai, China. Participants in both groups received treatment at the affected knee(s) at the acupuncture point Dubi (ST 35) and an Ashi point. There were 3 sessions per week for 4 weeks, and an additional 20-week follow-up. Primary outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores at week 4. Secondary outcomes were WOMAC function score, stiffness score and overall score, VAS pain, Short-Form heath survey (SF-36), and patients' global assessment. The serum levels of cytokines involved in progress of knee OA were explored. Safety was assessed during the whole trial. Masking effectiveness was assessed by both participants and treatment providers.This is a protocol for a multicenter, randomized, double-blind, placebo-controlled trial. A total of 392 participants were recruited and assigned to the CO laser moxibustion group and sham laser moxibustion group with a 1:1 ratio at 6 outpatient clinics in Shanghai, China. Participants in both groups received treatment at the affected knee(s) at the acupuncture point Dubi (ST 35) and an Ashi point. There were 3 sessions per week for 4 weeks, and an additional 20-week follow-up. Primary outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores at week 4. Secondary outcomes were WOMAC function score, stiffness score and overall score, VAS pain, Short-Form heath survey (SF-36), and patients' global assessment. The serum levels of cytokines involved in progress of knee OA were explored. Safety was assessed during the whole trial. Masking effectiveness was assessed by both participants and treatment providers.@*DISCUSSION@#CO laser moxibustion device, designed as a substitute for CM moxibustion, is easy to use and control with no choking smoke and smell, and is a plausible method for double-blind research. This study would provide rigorous evidence for the effect and safety of CO laser moxibustion in treating knee OA (Trial registration No.: ISRCTN15030019).

Diagnostic value of lymphocyte subset classification for active pulmonary tuberculosis in renal transplant recipients / 器官移植

Objective To evaluate the clinical value of lymphocyte subset classification in the diagnosis of active pulmonary tuberculosis in renal transplant recipients. Methods Clinical data of 52 recipients undergoing renal transplantation were retrospectively analyzed. According to the results of imaging and etiological examination, 52 recipients were divided into the stable group(n=19), tuberculosis group (n=9), bacteria group (n=12) and fungi group (n=12), respectively. The renal function of recipients was compared, and the proportion and absolute value of lymphocyte subset were analyzed and compared among four groups. The diagnostic value of lymphocyte subset classification for active pulmonary tuberculosis after renal transplantation was evaluated. Results Compared with the stable group, the levels of blood urea nitrogen and serum creatinine in the tuberculosis group, bacteria group and fungi group were significantly increased (all P < 0.05). The proportion of CD3+, CD8+, CD4+, natural killer (NK) cells and CD19+ lymphocyte subsets were not significantly different (all P>0.05). And the absolute values of CD3+, CD8+, CD4+, NK cells and CD19+ lymphocyte subsets were significantly decreased (all P < 0.05). The proportion of CD8+ lymphocyte subset in the tuberculosis group and fungi group was significantly higher than that in the bacteria group (both P < 0.05). The optimal cut-off value of CD8+ lymphocyte subset ratio in the differential diagnosis of active pulmonary tuberculosis and bacterial pneumonia was 33.27%, and the sensitivity and specificity were 0.889 and 0.833, respectively. The area under the curve (AUC) was 0.880. Conclusions The classification of lymphocyte subset can provide auxiliary diagnostic basis for differential diagnosis and individualized treatment of active pulmonary tuberculosis and bacterial pneumonia in renal transplant recipients.

Remote monitoring of neonatal jaundice in newborns with ABO hemolytic disease / 浙江大学学报·医学版

OBJECTIVE@#To explore the feasibility of remote monitoring of neonatal jaundice in newborns with ABO hemolytic disease.@*METHODS@#Forty six neonates of gestational age >35 weeks with ABO hemolytic disease admitted to Women's Hospital, Zhejiang University School of Medicine from January 20th, 2020 to February 29th, 2020 were enrolled in the study (study group). The newborns were followed up at home after discharge, the transcutaneous bilirubin (TCB) levels were measured by parents using the provided device and the results were sent to the doctor by smart phone using the installed APP. Fifty six newborns with ABO hemolytic disease admitted in 2018 who received conventional outpatient follow-up after discharge served as the control group. The demographic characteristics, total serum bilirubin (TSB) level during hospitalization, number of outpatient visit and rate of re-admission due to rebound hyperbilirubinemia were compared between the two groups.@*RESULTS@#There were no significant differences between the two groups in gestational age, birth weight, delivery mode, gender, length of the first hospitalization, TSB level before phototherapy and before discharge, and the managements during the first hospitalization (all @*CONCLUSIONS@#The remote follow-up for neonatal jaundice at home can effectively reduce the number of outpatient visits without increasing the risk of readmission and severe neonatal hyperbilirubinemia for newborns with ABO hemolytic disease.

Analysis on the temperature-time curve in warm needling manipulation with acupuncture needles of different materials / 中国针灸

OBJECTIVE@#To analyze the characteristics of the temperature-time curve in warm needling manipulation with the acupuncture needles made of copper, silver, gold and stainless steel and explore the applicable temperature range and most suitable needle materials of warm needling manipulation in clinical practice.@*METHODS@#A total of 10 healthy subjects were included. Using the digital thermometer, with different moxibustion dose (1.2 g or 1.5 g, moxa), the temperature was measured at the site where the skin contacts with the needle body during the warm needling manipulation with stainless steel needle, copper needle, gold needle and sliver needle separately. The initial heat pain threshold (the temperature when hot feeling started) and the burning pain threshold (feeling very hot but tolerable) were recorded when using the different needles mentioned above. Through the subject questionnaire, the comfort degree, the heat sensation, the adverse reaction and the acceptability to warm needling manipulation with the different needles were investigated.@*RESULTS@#During the warm needling manipulation, the initial heat pain threshold was (42.8±2.7) ℃ and the burning pain threshold was (46.7±2.9) ℃. The strongest warm stimulation was presented in the warm needling manipulation with 1.5 g moxa and silver needle and the highest temperature was (55.5±6.3) ℃, followed by (52.9±4.2) ℃ with 1.2 g moxa and silver needle, (46.6±3.7) ℃ with 1.5 g moxa and gold needle, (46.6±1.9) ℃ with 1.5 g moxa and copper needle, (43.1±1.5) ℃ with 1.2 g moxa and copper needle and (41.7±0.9) ℃ with 1.5 g moxa and stainless steel needle. The sequence of the maintaining time of the initial heat pain threshold over 43℃ was 480 s with silver needle and 1.5 moxa, 325 s with silver needle and 1.2 g moxa, 270 s with gold needle and 1.5 g moxa, 185 s with copper needle and 1.5 g moxa, 42 s with copper needle and 1.2 g moxa and 0 s with stainless steel needle and 1.5 g moxa successively. The heat score graded by the subjects to the warm needling manipulation with different needles, from high to low, was presented in the manipulation with 1.5 g moxa and silver needle, 1.2 g moxa and silver needle, 1.5 g moxa and copper needle, 1.5 g moxa and gold needle, 1.2 g moxa and copper needle and 1.5 g moxa and stainless steel needle. The VAS score was different significantly in comparison among the six needles in warm needling manipulation (<0.001). The comfort degree of the subjects in the warm needling manipulation with silver needle and 1.5 g moxa was significantly lower than the warm needling manipulation with the other 5 materials (<0.05). Three subjects complained that the warm needling manipulation with silver needle and 1.5 g moxa was too hot to be tolerable and the most of subjects were willing to accept warm needling manipulation with these 6 materials (acceptability 70.0% to 100.0%). Except blisters presented in 9 subjects after warm needling manipulation with silver needle and 1.5 g moxa, no severe adverse reaction occurred in warm needling manipulation with 6 materials.@*CONCLUSION@#In the warm needling manipulation in the human body, the initial heat pain and the burning pain threshold were 43 ℃ and 47 ℃ respectively, which is the applicable temperature range of moxibustion in clinical practice. The warm needling manipulation with silver needle induces a quite strong heat stimulation and the discomfort may be caused when the temperature is exceeded to some threshold. The warm needling manipulation with copper needle generates the onset temperature, without inducing adverse reactions, e.g. discomfort and burning in the subjects.

Clinical application of piggyback liver transplantation and modified surgery / 中华消化外科杂志

Orthotopic liver transplantation (OLT) was first implemented by Starzl in 1963.With the development of liver transplantation,Tzaris was the first to report piggyback liver transplantation (PBLT) in 1989.The fundamental difference between OLT and PBLT:end to end vascular anastomosis between the donor and recipient is performed after diseased liver resection with the posthepatic inferior vena cava in OLT,while PBLT is to preserve the recipient's hepatic vein and end to end vascular anastomosis between interior vena cava of donor and shaped hepatic vein is performed.However in the clinical practice,the above two techniques cannot meet the needs of clinical liver transplantation technology.Since 1993 the author has implemented a series of improvements in liver transplantation technology based on PBLT and performed ameliorated piggyback liver transplantation (APBLT).This article focuses on the technical characteristics and clinical application of APBLT.

A case of nephrectomy with strong positive HLA antibody undergoing the third renal transplantation / 中南大学学报(医学版)

The positive human leukocyte antigen (HLA) antibody present in kidney transplant recipients affects both surgery and rejection, and also affects the long-term survival of the transplanted kidney. During the third kidney transplant, bilateral axillary fossa and iliac vessel were destroyed. It was very difficult for selection or separation of surgical vessels because the adhesions and scar formation was easy to damage blood vessels and intestinal tubes. A case with strong positive HLA antibody undergoing the third kidney transplant in our hospital was successfully solved the problems, such as less transplant space and vascular scar adhesion. Rituximab, rabbit anti-human thymocyte immunoglobulin, and methylprednisolone treated-antibodies were used in the operation. The immune function test was used to develop individualized treatment after the operation. The postoperative creatinine and urine volume tended to be stable, and the 16-month follow-up renal function was good.