Genetic polymorphism of WNT9A is functionally associated with thumb osteoarthritis in the Chinese population

Abstract Background In a recent genome-wide association study, novel genetic variations of WNT9A were reported to be involved in the etiopathogenesis of thumb osteoarthritis (TOA) in Caucasians. Our purposes were to replicate the association of WNT9A with the development of TOA in the Chinese population and to further unveil the functional role of the risk variants. Methods SNP rs11588850 of WNT9A were genotyped in 953 TOA patients and 1124 healthy controls. The differences of genotype and allele distributions between the patients and healthy controls were evaluated using the Chi-square test. Luciferase Reporter Assay was performed to investigate the influence of variant on the gene expression. Results There was significantly lower frequency of genotype AA in TOA patients than in the controls 74.9% vs. 81.9%, p < 0.001). The frequency of allele A was remarkably lower in the patients than in the controls (86.3% vs. 90.5%, p < 0.001), with an odds ratio of 0.66 (95% CI = 0.54-0.80). Luciferase Reporter Assay showed that the construct containing mutant allele G of rs11588850 displayed 29.1% higher enhancer activity than the wild allele A construct (p < 0.05). Conclusions Allele G of rs11588850 was associated with the increased risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA. Key Points Genetic variants of WNT9A were associated with the incidence and severity of TOA. Allele G of rs11588850 was associated with an increased transcriptional activity of WNT9A promoter. Allele G of rs11588850 may add to the risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA.

Multi-slice CT imaging characteristics of distal tibiofibular syndesmosis in healthy adults / 中华创伤杂志

Objective:To measure the morphological parameters of distal tibiofibular syndesmosis in healthy adults using multi-slice CT (MSCT) so as to provide a reference for the diagnosis of distal tibiofibular syndesmosis injury.Methods:The ankle MSCT imaging data in 110 normal adults were retrieved from the image report database of Cangzhou People′s Hospital from May 2019 to May 2021, including 56 males and 54 females; aged 18-60 years [(38.2±11.0)years]. There were 51 patients with imaging on the right ankle and 59 on the left ankle. Picture archiving and communication system (PACS) was used to measure parameters at 10 mm above the articular surface of the distal tibia on MSCT, including the anterior tibiofibular space (L1), posterior tibiofibular space (L2), middle tibiofibular space (L3), depth of fibula in notch (L4), distance of anterior tibiofibular edge (L5), distance of posterior tibiofibular edge (L6), anterior tibiofibular syndesmosis angle (A1), and fibular rotation angle (A2), and the measurements were compared by sex, age and side. The positive rate of "tibiofibular line" was observed. The morphological classification of distal tibiofibular syndesmosis was performed.Results:There was no significant difference in L1-L6, A1 and A2 among different age and side (all P>0.05). No significant difference was found in L4, L5, A1 and A2 between males and females ( P>0.05), but L1, L2, L3 and L6 were larger in males than in females ( P<0.05 or 0.01). The positive rate of "tibiofibular line" was 80.4% (45/56) in males compared to 74.1% (40/54) in females ( P>0.05), 77.2% (44/57) in the youth compared to 77.4% (41/53) in the middle-aged, and 78.0% (46/59) in the left ankle compared to 76.5% (39/51) in the right ankle (all P>0.05). Morphological classification of distal tibiofibular syndesmosis was crescent in 61 patients (55.5%), trapezoid in 14 (12.7%), I-shaped in 3 (2.7%), M-shaped in 17 (15.5%), V-shaped in 10 (9.1%), Г-shaped in 5 (4.5%). Conclusions:When L1, L2, L3 and L6 are used as references in the diagnosis of adult distal tibiofibular syndesmosis injury, gender factors rather than age or side factors should be considered. Males have wider distal tibiofibular space than females, with the fibula more forward. The "tibiofibular line" has a high positive rate and is not affected by gender, age or sides, providing a new idea for the diagnosis of distal tibiofibular syndesmosis injury and anatomical reduction. There are many variations in the morphology of distal tibiofibular syndesmosis, so it is easy to be misdiagnosed as the separation of distal tibiofibular syndesmosis on X-ray, which should be noted.

Study on deep brain magnetic stimulation method based on magnetic replicator / 生物医学工程学杂志

Existing neuroregulatory techniques can achieve precise stimulation of the whole brain or cortex, but high-focus deep brain stimulation has been a technical bottleneck in this field. In this paper, based on the theory of negative permeability emerged in recent years, a simulation model of magnetic replicator is established to study the distribution of the induced electric field in the deep brain and explore the possibility of deep focusing, which is compared with the traditional magnetic stimulation method. Simulation results show that a single magnetic replicator realized remote magnetic source. Under the condition of the same position and compared with the traditional method of stimulating, the former generated smaller induced electric field which sharply reduced with distance. By superposition of the magnetic field replicator, the induced electric field intensity could be increased and the focus could be improved, reducing the number of peripheral wires while guaranteeing good focus. The magnetic replicator model established in this paper provides a new idea for precise deep brain stimulation, which can be combined with neuroregulatory techniques in the future to lay a foundation for clinical application.

Analyzing the current status of newly diagnosed occupational pneumoconiosis patients in Zhangdian District of Zibo City / 中国职业医学

Objective To analyze the distribution, survival conditions, and medical support of newly diagnosed occupational pneumoconiosis (hereinafter referred to as pneumoconiosis) patients in Zhangdian District, Zibo City. Methods A total of 1 189 newly diagnosed pneumoconiosis patients in Zhangdian District from 1956 to 2019 were selected as the study subjects using retrospective method. Data of their age of onset, years of occupational exposure, category of working industry, type of pneumoconiosis, and status of medical support was collected and analyzed. Results The median and the 25th-75th percentiles ［M (P25, P75)］ of the age of onset were 51.8 (45.5, 56.1) years, and the mortality was 37.0%. The majority of pneumoconiosis cases were silicosis (45.2%) and coal workers' pneumoconiosis (39.8%). The highest prevalence of pneumoconiosis was in the coal mining and washing industry (42.4%), followed by manufacturing (33.4%). Pneumoconiosis patients in stage Ⅰ,Ⅱ, and Ⅲ accounted for 89.1%, 8.7%, and 2.2%, respectively. The M (P25, P75) of the length of work exposed to dust were 24.1 (16.5, 29.9) years.The higher stage of pneumoconiosis the shorter of the length of work exposed to dust among these pneumoconiosis patients(all P<0.05). The overall survival rate, the 5-year survival rate and the 10-year survival rate of these pneumoconiosis patients were 63.0%, 92.3% and 85.9%, respectively. Among the 749 surviving cases, 60.8% were aged 60.0 to <80.0 years. In terms of social security, 100.0% surviving cases enjoyed basic medical insurance, meanwhile, 96.1% and 81.8% patients were covered by major medical insurances and occupational injury insurances, respectively. The M (P25, P75) of age at death were 73.1 (64.0, 77.1) years. The main causes of death were respiratory diseases (59.3%) and malignant tumors (20.4%). Conclusion The prevalent types of pneumoconiosis in Zhangdian District, Zibo City, are coal workers' pneumoconiosis and silicosis. Medical support and assistance are relatively limited. The pneumoconiosis prevention and control focus should be on silicosis and coal workers' pneumoconiosis, particularly in the manufacturing industry.

Associations of TNF-RII rs1061622 With Post-Traumatic Stress Disorder and Their Interplays on Serum Lipids Levels in Adolescents

Objective@#To verify effects of rs1061622 at tumor necrosis factor-α receptor II (TNF-RII) gene (TNF-RII) on post-traumatic stress disorder (PTSD) and its interactive effects with PTSD on serum lipids levels in adolescents. @*Methods@#PTSD was measured by PTSD Checklist-Civilian Version (PCL-C) in 699 adolescent survivors at 6 months after Wenchuan earthquake in China. A polymerase chain reaction and restriction fragment length polymorphism assay were utilized for TNF-RII rs1061622 genotyping followed by verification using DNA sequencing. Serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol were tested using routine methods. @*Results@#G (deoxyguanine) allele carriers had higher PCL-C scores than TT (deoxythymidine) homozygotes in female subjects. Female adolescents had higher PCL-C scores than male subjects in TT homozygotes. Predictors of PTSD prevalence and severity were different between G allele carriers and TT homozygotes. Subjects with PTSD had lower TG, TG/HDL-C, TC/HDL-C, and higher HDL-C than adolescents without PTSD in male G allele carriers. G allele carriers had higher TG/HDL-C and TC/HDL-C than TT homozygotes in male adolescents without PTSD, and lower TG and TG/HDL-C in male PTSD patients. G allele carriers had higher TG than TT homozygotes only in female adolescents without PTSD. @*Conclusion@#These results suggest reciprocal actions of TNF-RII rs1061622 with other factors on PTSD severity, interplays of TNF-RII rs1061622 with PTSD on serum lipid levels, and novel treatment strategies for PTSD and comorbidities of PTSD with hyperlipidemia among adolescents with different genetic backgrounds of TNF-RII rs1061622 after experiencing traumatic events.

Pooled analysis of the ophthalmic visual quality of life questionnaire scale / 国际眼科杂志(Guoji Yanke Zazhi)

With people's attention and in-depth research on visual quality, many distinctive survey scales have been developed. The use of visual quality questionnaires is a subjective way to evaluate patients' visual quality, an expression of patients' self feelings, and an important part of reflecting visual quality. With objective detection methods, the results are more convincing. Many scales have been introduced into China and have been revised through translation, back translation, and cultural adaptation, playing an indispensable role in the visual quality evaluation system. It is particularly important to assess visual quality through psychological and sociological content, and whether the content can be appropriately combined with the subjective feelings of patients. The core of the visual quality of life survey questionnaire lies in its high repeatability. This article summarizes commonly used visual quality questionnaires, which have been verified in terms of validity, reliability, and responsiveness. The validity of the measurement scale, the consistency of the measurement results, the ability to reflect the smallest meaningful clinical changes after effective medical intervention, and the design characteristics, main application directions, and trends of the scale are listed to provide reference for clinical workers to choose appropriate survey scales.

Clinical analysis of perioperative safety and short-term prognosis of non-small cell lung cancer patients with preoperative arrhythmia / 中国胸心血管外科临床杂志

@#Objective    To analyze the perioperative safety and the short-term prognosis of non-small cell lung cancer (NSCLC) patients with preoperative arrhythmia. Methods    The clinical data of NSCLC patients treated in the Department of Cardiothoracic Surgery, the First Affiliated Hospital of Chongqing Medical University from August 2020 to March 2021 were collected and observed. The patients were divided into an arrhythmia group and a control group according to whether there was arrhythmia in the 24 h ambulatory electrocardiogram examination report before operation. The incidence of intraoperative and postoperative cardiovascular events and short-term prognosis were compared between the two groups. Results     A total of 466 patients were included in this study, including 338 patients in the arrhythmia group, 176 males and 162 females, with a median age of 68.0 (63.0, 72.0) years, and 128 patients in the control group, 59 males and 69 females, with a median age of 66.5 (60.0, 72.0) years. A total of 26 patients (7.7%) in the arrhythmia group were placed with temporary pacemakers before operation. There was no significant difference in the incidence of cardiovascular related events between the two groups [100 (29.6%) vs. 28 (21.9%), P=0.096]. The incidence of postoperative arrhythmia events in the arrhythmia group was higher than that in the control group [112 (33.1%) vs. 11 (8.6%), P<0.001]. The average postoperative ICU stay in the arrhythmia group was longer than that in the control group (1.1±0.7 d vs. 1.0±0.6 d, P=0.039). Conclusion    Preoperative arrhythmia does not increase the risk of intraoperative cardiovascular events in NSCLC patients, but increases the incidence of postoperative arrhythmia events and prolongs ICU stay.

Clinical characteristics and risk factors of superior mesenteric artery ischemic disease / 中华普通外科杂志

Objective:To explore the clinical characteristics of superior mesenteric artery ischemic diseases.Methods:The clinical and followup data of 141 hospitalized patients with ischemic disease of superior mesenteric artery in the Affiliated Hospital of Southwest Medical University from 1999 to 2021 were reviewed.Results:There were 99 males (70.2%) and 42 females (29.8%). The average age of the patients was (63.75±13.16) years; 127 patients (90.1%) complained abdominal pain.The number of all-cause deaths in the perioperative period was 27 (19.1%). ROC curve analysis showed that the optimal cutoff value of the age with predictive value was 64.5 years. The results of multivariate COX regression analysis showed that age ≥65 years old ( HR=3.855, 95% CI: 1.739-8.545), neutrophil count ( HR=1.072, 95% CI: 1.018-1.130), heart failure ( HR=2.863, 95% CI: 1.332-6.154), creatinine ( HR=1.009, 95% CI: 1.003-1.015), D-Dimer ( HR=1.112, 95% CI: 1.025-1.205) was an independent risk factor for all-cause death from superior mesenteric artery ischemic disease. Long-term survival rate of SMAD group was significantly higher than that of other SMAID; By comparing the clinical characteristics of different SMAID, neutrophil count, neutrophil ratio, D-dimer of SMAE group and SMAT group were significantly higher than that of SMAD group and ASSMA group. Conclusions:SMAID usually occurs in elderly men over 65 years old, with abdominal pain as the main symptom and often accompanied by hypertension. Risk factors included age, increased WBC count and D-dimer; The neutrophil count, neutrophil ratio, D-dimer in SMAE and SMAT group were significantly higher than that of SMAD and ASSMA group.

Comparison of clinical efficacy between laparoscopic and open radical resection of hilar cholangiocarcinoma / 中华普通外科杂志

Objective:To evaluate the efficacy of total laparoscopic surgery vs. open surgery for hilar cholangiocarcinoma. Methods:The clinical data of 45 patients undergoing laparoscopic radical resection of hilar cholangiocarcinoma and 42 patients by open surgery from Mar 2017 to Mar 2021 were retrospectively analyzed.Results:There was no significant difference in demographics, Bismuth classification and excision extension between the two groups (all P>0.05). The laparoscopic surgery used longer time ( t=-1.366, P<0.05). The intraoperative blood loss, number of lymph node dissection and postoperative hospital stay favored laparoscopic method( t=0.043, t=0.026, t=-1.852, P<0.05). R 0 radical resection rate，postoperative complications were also in favor of laparoscopic surgery ( χ2=3.216, χ2=2.566, all P<0.05). There was no significant difference in postoperative pathology and in hospital expenses (all P>0.05). The 1- and 3-year survival rate of the laparoscopic group was superior (all P<0.05). Conclusions:In spite of longer operational time，patients in laparoscopic hilar cholangiocarcinoma radical resection group have shorter postoperative in hospital stay and longer postoperative survival time.

Transanal drainage tube for prevention of anastomotic leak after anterior resection for rectal cancer: a meta-analysis / 中华胃肠外科杂志

Objective: To assess the effectiveness of transanal drainage tube (TDT) in reducing the incidence of anastomotic leak following anterior resection in patients with rectal cancer. Methods: We conducted a systematic search for relevant studies published from inception to October 2022 across multiple databases, including PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP. Meta-analysis was performed using Review Manager 5.4 software. The primary outcomes included total incidence of anastomotic leak, grade B and C anastomotic leak rates, reoperation rate, anastomotic bleeding rate, and overall complication rate. Results: Three randomized controlled trials involving 1115 patients (559 patients in the TDT group and 556 in the non-TDT group) were included. Meta-analysis showed that the total incidences of anastomotic leak and of grade B anastomotic leak were 5.5% (31/559) and 4.5% (25/559), respectively, in the TDT group and 7.9% (44/556) and 3.8% (21/556), respectively, in the non-TDT group. These differences are not statistically significant (P=0.120, P=0.560, respectively). Compared with the non-TDT group, the TDT group had a lower incidence of grade C anastomotic leak (1.6% [7/559] vs. 4.5% [25/556]) and reoperation rate (0.9% [5/559] vs. 4.3% [24/556]), but a higher incidence of anastomotic bleeding (8.2% [23/279] vs. 3.6% [10/276]). These differences were statistically significant (P=0.003, P=0.001, P=0.030, respectively). The overall complication rate was 26.5%(74/279) in the TDT group and 27.2% (75/276) in the non-TDT group. These differences are not statistically significant (P=0.860). Conclusions: TDT did not significantly reduce the total incidence of anastomotic leak but may have potential clinical benefits in preventing grade C anastomotic leak. Notably, placement of TDT may increase the anastomotic bleeding rate.

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.

The beginnings and evolution of a pancreatic surgeon: a technical morphological analysis in first 5 years / 中华外科杂志

Objective: To explore the development of the pancreatic surgeon technique in a high-volume center. Methods: A total of 284 cases receiving pancreatic surgery by a single surgeon from June 2015 to December 2020 were retrospectively included in this study. The clinical characteristics and perioperative medical history were extracted from the medical record system of Zhongshan Hospital,Fudan University. Among these patients,there were 140 males and 144 females with an age (M (IQR)) of 61.0 (16.8) years(range: 15 to 85 years). The "back-to-back" pancreatic- jejunal anastomosis procedure was used to anastomose the end of the pancreas stump and the jejunal wall. Thirty days after discharge,the patients were followed by outpatient follow-up or telephone interviews. The difference between categorical variables was analyzed by the Chi-square test or the CMH chi-square test. The statistical differences for the quantitative data were analyzed using one-way analysis of variance or Kruskal-Wallis H test and further analyzed using the LSD test or the Nemenyi test,respectively. Results: Intraoperative blood loss in pancreaticoduodenectomy between 2015 and 2020 were 300,100(100),100(100),100(0),100(200) and 150 (200) ml,respectively. Intraoperative blood loss in distal pancreatectomy was 250 (375),100 (50),50 (65), 50 (80),50 (50),and 50 (100) ml,respectively. Intraoperative blood loss did not show statistical differences in the same operative procedure between each year. The operative time for pancreaticoduodenectomy was respectively 4.5,5.0(2.0),5.5(0.8),5.0(1.3),5.0(3.3) and 5.0(1.0) hours in each year from 2015 to 2020,no statistical differences were found between each group. The operating time of the distal pancreatectomy was 3.8 (0.9),3.0 (1.5),3.0 (1.8),2.0 (1.1),2.0 (1.5) and 3.0(2.0) hours in each year,the operating time was obviously shorter in 2018 compared to 2015 (P=0.026) and 2020 (P=0.041). The median hospital stay in 2020 for distal pancreatectomy was 3 days shorter than that in 2019. The overall incidence of postoperative pancreatic fistula gradually decreased,with a incident rate of 50.0%,36.8%,31.0%,25.9%,21.1% and 14.8% in each year. During this period,in a total of 3,6,4,2,0 and 20 cases received laparoscopic operations in each year. The incidence of clinically relevant pancreatic fistula (grade B and C) gradually decreased,the incident rates were 0,4.8%,7.1%,3.4%,4.3% and 1.4%,respectively. Two cases had postoperative abdominal bleeding and received unscheduled reoperation. The overall rate of unscheduled reoperation was 0.7%. A patient died within 30 days after the operation and the overall perioperative mortality was 0.4%. Conclusion: The surgical training of a high-volume center can ensure a high starting point in the initial stage and steady progress of pancreatic surgeons,to ensure the safety of pancreatic surgery.

Overview and reflection on the development of the first batch of the inheritance studios of acupuncture and moxibustion academic schools / 中国针灸

The development status of the first 11 inheritance studios of acupuncture and moxibustion academic schools is summarized. Aiming at the current problems, it is suggested to establish qualitative and quantitative evaluation standards and establish a fair and reasonable evaluation system, build a systematic scientific theory and excavate the inherent laws of the schools, implement standardized management of the schools and protect the personalized characteristics of the schools, open outpatient clinic of acupuncture and moxibustion schools and promote the characteristic diagnosis and treatment technology, to promote the inheritance and development of acupuncture and moxibustion academic schools.

Brief introduction of Qilu modern acupuncture methods / 中国针灸

Qilu acupuncture and moxibustion has promoted the formation and development of traditional Chinese medicine, which has a special historical position. By systematically collecting, sorting out and summarizing the characteristic acupuncture methods and academic ideas of several Qilu acupuncturists since the founding of the People's Republic of China, the understanding of the advantages and characteristics of Qilu modern acupuncture methods is deepened, aiming to exploring the inheritance and development pattern of Qilu acupuncture methods in the new era.

Metabonomic Analysis of Wenfei Huaxian Granules Against Idiopathic Pulmonary Fibrosis in Mice / 中国实验方剂学杂志

ObjectiveTo investigate the changes of differential metabolites in the serum of mice at different stages of bleomycin sulfate（BLM）-induced pulmonary fibrosis modeling and administration， and the mechanism of Wenfei Huaxian granules（WHG）against idiopathic pulmonary fibrosis. MethodMice were randomly divided into control group， control group of 14 days， model group， model group of 14 days， low-dose WHG group and high-dose WHG group. BLM（0.04 U per mouse）was injected into the trachea of mice in the model group， model group of 14 days， low-dose WHG group and high-dose WHG group， and sterile normal saline was injected into the trachea of mice in the control group and control group of 14 days. Mice of low-dose WHG group and high-dose WHG group were given different doses of WHG by gavage every day after injection of BLM， and mice of control group， control group of 14 days， model group and model group of 14 days were given sterile water by gavage every day. The peripheral blood of mice in the control group of 14 days and model group of 14 days were taken to prepare serum after injection of BLM for 14 days， and the peripheral blood and other materials of mice in the other groups were taken after continuous administration for 28 days. The bronchoalveolar lavage fluid（BALF）was collected for leucocyte differential count， the pathological examination and hydroxyproline（HYP）content determination of lung tissues of mice were performed， and the small molecule metabolites in serum samples of mice in each group were determined by ultra-high performance liquid chromatography-mass spectrometry（UHPLC-MS）. Principal component analysis（PCA）and orthogonal partial least squares-discriminant analysis（OPLS-DA）were conducted to screen differential metabolites and their biological functions were analyzed. ResultCompared with the control group， a large number of continuous fibrotic foci appeared in the lung tissue of mice in the model group， the alveolitis score， fibrosis degree score and HYP content increased significantly（P<0.01）， and the total number of leukocytes， macrophages and lymphocytes in BALF increased significantly（P<0.05）. A total of 33 differential metabolites were screened between the control group of 14 days and model group of 14 days， mainly lipid metabolites， which were mainly involved in oxidative damage and inflammatory process. A total of 34 differential metabolites， mainly amino acid metabolites， were screened between the control group and model group， mainly involving nucleic acid damage and inflammatory process. Compared with the model group， the HYP content， fibrosis score and alveolitis score in the lung tissue of mice from high-dose WHG group decreased significantly（P<0.05， P<0.01）， and the total number of lymphocytes in BALF decreased significantly（P<0.05）. Compared with the model group， 27， 40 differential metabolites were identified in the serum of mice from the low-dose WHG group and high-dose WHG group separately. There were totally 9 common differential metabolites between the model group and low-dose WHG group/high-dose WHG group， which mainly involved in the metabolic pathways of inflammation related lipids metabolism， arginine and tryptophan metabolism， and the change trends in low-dose WHG group and high-dose WHG group were significantly back-regulated compared with the model group. ConclusionWHG can alleviate BLM-induced pulmonary fibrosis， collagen deposition and inflammatory reaction in mice， and its anti-fibrotic effect may be related to the adjusting of inflammatory factors， nitric oxide and oxidative stress related metabolic pathways.

The influence of tissue conductivity on the calculation of electric field in the transcranial magnetic stimulation head model / 生物医学工程学杂志

In transcranial magnetic stimulation (TMS), the conductivity of brain tissue is obtained by using diffusion tensor imaging (DTI) data processing. However, the specific impact of different processing methods on the induced electric field in the tissue has not been thoroughly studied. In this paper, we first used magnetic resonance image (MRI) data to create a three-dimensional head model, and then estimated the conductivity of gray matter (GM) and white matter (WM) using four conductivity models, namely scalar (SC), direct mapping (DM), volume normalization (VN) and average conductivity (MC), respectively. Isotropic empirical conductivity values were used for the conductivity of other tissues such as the scalp, skull, and cerebrospinal fluid (CSF), and then the TMS simulations were performed when the coil was parallel and perpendicular to the gyrus of the target. When the coil was perpendicular to the gyrus where the target was located, it was easy to get the maximum electric field in the head model. The maximum electric field in the DM model was 45.66% higher than that in the SC model. The results showed that the conductivity component along the electric field direction of which conductivity model was smaller in TMS, the induced electric field in the corresponding domain corresponding to the conductivity model was larger. This study has guiding significance for TMS precise stimulation.

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.

Effect of advanced paternal age on reproductive outcomes in IVF cycles of non-male-factor infertility: a retrospective cohort study / 亚洲男科学杂志(英文版)

Advanced paternal age has been overlooked, and its effect on fertility remains controversial. Previous studies have focused mainly on intracytoplasmic sperm injection (ICSI) cycles in men with oligozoospermia. However, few studies have reported on men with semen parameters within reference ranges. Therefore, we conducted a retrospective cohort study analyzing the reproductive outcomes of couples with non-male-factor infertility undergoing in vitro fertilization (IVF) cycles. In total, 381 cycles included were subgrouped according to paternal age (<35-year-old, 35-39-year-old, or ≥40-year-old), and maternal age was limited to under 35 years. Data on embryo quality and clinical outcomes were analyzed. The results showed that fertilization and high-quality embryo rates were not significantly different (all P > 0.05). The pregnancy rate was not significantly different in the 35-39-year-old group (42.0%; P > 0.05), but was significantly lower in the ≥40-year-old group (26.1%; P < 0.05) than that in the <35-year-old group (40.3%). Similarly, the implantation rate significantly decreased in the ≥40-year-old group (18.8%) compared with that in the <35-year-old group (31.1%) and 35-39-year-old group (30.0%) (both P < 0.05). The live birth rate (30.6%, 21.7%, and 19.6%) was not significantly different across the paternal age subgroups (<35-year-old, 35-39-year-old, and ≥40-year-old, respectively; all P > 0.05), but showed a declining trend. The miscarriage rate significantly increased in the 35-39-year-old group (44.8%) compared with that in the <35-year-old group (21.0%; P < 0.05). No abnormality in newborn birth weight was found. The results indicated that paternal age over 40 years is a key risk factor that influences the assisted reproductive technology success rate even with good semen parameters, although it has no impact on embryo development.

Guidelines for management of pediatric acute hyperextension spinal cord injury / 中华创伤杂志(英文版)

Pediatric acute hyperextension spinal cord injury (SCI) named as PAHSCI by us, is a special type of thoracolumbar SCI without radiographic abnormality and highly related to back-bend in dance training, which has been increasingly reported. At present, it has become the leading cause of SCI in children, and brings a heavy social and economic burden. Both domestic and foreign academic institutions and dance education organizations lack a correct understanding of PAHSCI and relevant standards, specifications or guidelines. In order to provide standardized guidance, the expert team formulated this guideline based on the principles of science and practicability, starting from the diagnosis, differential diagnosis, etiology, admission evaluation, treatment, complications and prevention. This guideline puts forward 23 recommendations for 14 related issues.

Pancreatic melatonin enhances anti-tumor immunity in pancreatic adenocarcinoma through regulating tumor-associated neutrophils infiltration and NETosis

Tumor microenvironment contributes to poor prognosis of pancreatic adenocarcinoma (PAAD) patients. Proper regulation could improve survival. Melatonin is an endogenous hormone that delivers multiple bioactivities. Here we showed that pancreatic melatonin level is associated with patients' survival. In PAAD mice models, melatonin supplementation suppressed tumor growth, while blockade of melatonin pathway exacerbated tumor progression. This anti-tumor effect was independent of cytotoxicity but associated with tumor-associated neutrophils (TANs), and TANs depletion reversed effects of melatonin. Melatonin induced TANs infiltration and activation, therefore induced cell apoptosis of PAAD cells. Cytokine arrays revealed that melatonin had minimal impact on neutrophils but induced secretion of Cxcl2 from tumor cells. Knockdown of Cxcl2 in tumor cells abolished neutrophil migration and activation. Melatonin-induced neutrophils presented an N1-like anti-tumor phenotype, with increased neutrophil extracellular traps (NETs) causing tumor cell apoptosis through cell-to-cell contact. Proteomics analysis revealed that this reactive oxygen species (ROS)-mediated inhibition was fueled by fatty acid oxidation (FAO) in neutrophils, while FAO inhibitor abolished the anti-tumor effect. Analysis of PAAD patient specimens revealed that CXCL2 expression was associated with neutrophil infiltration. CXCL2, or TANs, combined with NET marker, can better predict patients' prognosis. Collectively, we discovered an anti-tumor mechanism of melatonin through recruiting N1-neutrophils and beneficial NET formation.