Sonogenetics and its application in military medicine / 解放军医学杂志

Sonogenetics is an emerging synthetic biology technique that uses sound waves to activate mechanosensitive ion channel proteins on the cell surface to regulate cell behavior and function.Due to the widespread presence of mechanically sensitive ion channel systems in cells and the advantages of non-invasion,strong penetrability,high safety and high accuracy of sonogenetics technology,it has great development potential in basic biomedical research and clinical applications,especially in neuronal regulation,tumor mechanism research,sonodynamic therapy and hearing impairment.This review discusses the basic principles of sonogenetics,the development status of sonogenetics and its application in the prevention and treatment of noise-induced hearing loss,summarizes and analyzes the current challenges and future development direction,thus providing a reference for further research and development of sonogenetics in the field of military medicine.

The quadrant method was used to assess the relationship between the type of cement distribution after vertebroplasty and new fractures of osteoporotic vertebral bodies / 临床外科杂志

Objective To evaluate the diffusion distribution of bone cement in the vertebral body by quadrant method,and to analyze and evaluate the correlation between the diffusion distribution type of bone cement and new vertebral fractures after vertebral augmentation.Methods A total of 170 subjects who met the conditions from January 2020 to December 2021 were collected.According to the anteroposterior and lateral view of the spine,the injured vertebra was divided into four quadrants,and divided into homogeneous diffusion group and uneven diffusion group according to the postoperative diffusion distribution of bone cement in the injured vertebra.The incidence and types of refracture were followed up,and the VAS score and Cobb angle were compared between the two groups.Results 170 patients were followed up for at least 12 months,including 90 patients in homogeneous diffusion group and 80 patients in heterogeneous diffusion group.There were 33 cases of refracture(19.41％),12 cases of refracture(13.33％)in the diffuse homogeneous group,and 21 cases of refracture(26.25％)in the diffuse heterogeneous group,and the difference between the groups was statistically significant(P＜0.05).The site of refracture in the diffuse homogeneous group was mainly the clinical vertebral fracture,while the probability of refracture in the diffuse heterogeneous clinical vertebra and the operated vertebra was similar.The incidence of postoperative bone cement leakage in the diffuse homogeneous group was significantly lower than that in diffuse heterogeneous group(P＜0.05).The VAS score and Cobb angle were significantly improved in both groups after surgery and at the last follow-up compared with those before surgery,but there was no significant difference between groups.Conclusion The incidence of new vertebral fractures after vertebroplasty is closely related to the type of cement diffusion,and the risk of refracture defined as uneven cement diffusion by quadrant method is high.

Clinical characteristics and prognosis of 28 cases of infant acute lymphoblastic leukemia / 中华儿科杂志

Objective: To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL). Methods: A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children's Hospital, Capital Medical University and Baoding Children's Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients. Results: Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) (χ2=1.88, 1.47, P=0.170, 0.224). Conclusions: Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

Fangji Fuling Decoction Alleviates Sepsis by Blocking MAPK14/FOXO3A Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To examine the therapeutic effect of Fangji Fuling Decoction (FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments.@*METHODS@#A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS). RAW264.7 cells were stimulated by 250 ng/mL LPS to establish an in vitro cell model. Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis. Through ectopic expression and depletion experiments, the effect of FFD on multiple organ damage in septic mice, as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A (MAPK14/FOXO3A) signaling pathway, was analyzed.@*RESULTS@#FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro (P<0.05). Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis. As confirmed by in vitro cell experiments, FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation (P<0.05). Furthermore, FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice (P<0.05).@*CONCLUSION@#FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.

Analysis of influencing factors for early tumor recurrence and efficacy of adjuvant chemotherapy in gallbladder carcinoma patients after curative-intent resection: a nationwide, multicenter clinical study / 中华消化外科杂志

Objective:To investigate the influencing factors for early tumor recurrence and the efficacy of adjuvant chemotherapy in gallbladder carcinoma (GBC) patients after curative-intent resection.Methods:The retrospective case-control study was conducted. The clinicopathological data of 506 patients with GBC in 11 medical centers, including The First Affiliated Hospital of Xi'an Jiaotong University et al, from January 2016 to December 2020 were collected. There were 168 males and 338 females, aged (62±11)years. All patients underwent curative-intent resection of GBC, and they were divided into patients with and without early recurrence based on time to postoperative recurrence. Observation indicators: (1) treatment; (2) follow-up and survival of patients; (3) analysis of influencing factors for early tumor recurrence after curative-intent resection of GBC; (4) efficacy of postoperative adjuvant chemotherapy. 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, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Mann-Whitney U test. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was conducted using the Logistic regression model with forward method. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and Log-Rank test was used for survival analysis. Results:(1) Treatment. Of 506 patients, there were 112 cases with postoperative adjuvant chemotherapy, and 394 cases without postopera-tive adjuvant chemotherapy. They underwent 5(range, 3-9)cycles of postoperative adjuvant chemo-therapy. (2) Follow-up and survival of patients. All 506 patients underwent postoperative follow-up, with the follow-up time of 55(range, 34-93)months. During the follow-up, there were 248 patients with tumor recurrence, including 158 cases of early recurrence and 90 cases of late recurrence, and there were 258 patients without tumor recurrence. Of 506 patients, 275 cases survived, and 231 cases died of multiple organ failure caused by tumor recurrence and metastasis. The postoperative recurr-ence-free survival time, overall survival time were 52(range,1-93)months, 62(range, 2-93)months. The 1-, 3-, 5-year disease-free survival rates and 1-, 3-, 5-year overall survival rates of the 506 pati-ents were 68.8%, 53.8%, 47.9% and 78.3%, 58.7%, 51.6%, respectively. Results of survival analysis showed that the median overall survival time of 158 patients with postoperative early recurrence and 348 patients without postoperative early recurrence (including 90 cases of late recurrence and 258 cases of no tumor recurrence) were 9(range, 2-73)months and unreached, showing a significant difference between them ( χ2=456.15, P<0.05). (3) Analysis of influencing factors for early tumor recurrence after curative-intent resection of GBC. Results of multivariate analysis showed that carcinoembryonic antigen (CEA) >5.0 μg/L, poorly differentiated tumor, liver invasion, and tumor N staging as stage N1-N2 were independent risk factors influencing early tumor recurrence after cura-tive-intent resection of GBC ( odds ratio=2.74, 6.20, 1.81, 2.93, 4.82, 95% confidence interval as 1.62-4.64, 1.82-21.12, 1.15-3.08, 1.68-5.09, 1.91-12.18, P<0.05), while postoperative adjuvant chemo-therapy was an independent protect factor ( odds ratio=0.39, 95% confidence interval as 0.21-0.71, P<0.05). (4) Efficacy of postoperative adjuvant chemotherapy. The median overall survival time of 394 patients without postoperative adjuvant chemotherapy and 112 patients with postoperative adjuvant chemotherapy were 57(range, 2-93)months and unreached, showing a significant differ-ence between them ( χ2=9.38, P<0.05). Of the 158 patients with postoperative early recurrence after curative-intent resection of GBC, 135 cases didn't receive adjuvant chemotherapy and 23 cases received adjuvant chemotherapy, with the overall survival time of 8(range, 2-73)months and 17(range, 8-61)months, respectively, showing a significant difference between them ( χ2=7.68, P<0.05). Conclusions:CEA >5.0 μg/L, poorly differentiated tumor, liver invasion, and tumor N staging as stage N1-N2 are independent risk factors influencing early tumor recurrence after curative-intent resection of GBC, while postoperative adjuvant chemotherapy is an independent protect factor. Postoperative adjuvant chemotherapy can prolong the overall survival time of patients with post-operative tumor early recurrence.

Prevalence of non-alcoholic fatty liver disease and associated factors in overweight and obese children in Hohhot / 中国学校卫生

Objective@#To explore prevalence and associated factors of nonalcoholic fatty liver disease (NAFLD) in overweight and obese children in Hohhot City, so as to provide the oretical basis for developing health education plans and implementing prevention and treatment of NAFLD in children.@*Methods@#A total of 156 overweight and obese children was enrolled from 4 primary schools in Hohhot City using cluster sampling method during 28th Aug. 2022 to 5th Mar. 2023. Height and weight were measured and body mass index was calculated, and fasting blood was taken in the early morning for fasting blood glucose, alanine aminotransferase, aspartate aminotransferase. Single factor analysis was conducted using ttest, χ2 test and Fishers exact probability method, while multivariate analysis was conducted using Logistic regression analysis and subject characteristic curves.@*Results@#The differences in age, waist circumference, hip circumference, fasting glucose, alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, uric acid, and triglyceride were statistically significant between the nonNAFLD and the NAFLD group (U/t=1 070.0-2 164.0, P<0.05). Significant differences were observed in aspartate aminotransferase (AST) and uric acid levels (AST OR=1.16, 95%CI=1.04-1.28; uric OR=1.01, 95%CI=1.00-1.01, P<0.05). The area under a receiver operating characteristic were 0.737 for aspartate aminotransferase and 0.665 for uric acid, respectively.@*Conclusions@#The prevalence of NAFLD is high in overweight/obese children in Hohhot, and both elevated aspartate aminotransferase and hyperuricemia could increase the risk of NAFLD in overweight/obese children. Special attention should be paid to the NAFLD in overweight and obese children. It is recommended to reduce both BMI and uric level in the prevention and treatment of NAFLD to achieve better treatment outcomes.

Effect and mechanism of PNU-282987 on cognitive function of temporal lobe epilepsy model rats / 中国药房

OBJECTIVE To investigate the effect and mechanism of α7 nicotinic acetylcholine receptor （α7nAChR） agonists PNU-282987 on cognitive function in temporal lobe epilepsy （TLE） model rats. METHODS Sixty rats were randomly divided into control group， model group， PNU-282987 group （3 mg/kg） and methyllycaconitine （MLA）+PNU-282987 group （6 mg/kg MLA+3 mg/kg PNU-282987）， with 15 rats in each group. Except for control group， the TLE model was established in the other groups. After the model was successfully established， each group was given relevant medicine or normal saline intraperitoneally， once a day， for two consecutive weeks. The epilepsy attack of rats was observed and scored， and the duration of seizures was recorded； the cognitive function of rats was detected； pathological morphology of neurons in CA1 region was observed； the levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in the hippocampus were detected； the positive expressions of ionized calcium-binding adapter molecule-1 （IBA-1）， α7nAChR， nuclear factor-κB （NF-κB） p65， p-NF-κB p65 in the hippocampus were detected. RESULTS Compared with model group， the score and duration of seizures， the number of IBA-1 positive cells， the levels of TNF- α， IL-6 and IL-1β， the expressions of NF- κB p65 and p-NF- κB p65 protein decreased significantly in the hippocampus （P＜0.05）； the escape latency time was shortened significantly （P＜0.05）， the time spent in the original platform quadrant and times of crossing the platform increased significantly （P＜0.05）； neuronal damage in the CA1 region of the hippocampus was significantly reduced； the expression of α7nAChR protein increased significantly in hippocampus （P＜0.05）. Compared with PNU-282987 group， the above indexes of rats in MLA+PNU-282987 group were reversed significantly （P＜0.05）. CONCLUSIONS PNU-282987 could improve cognitive dysfunction in TLE model rats， and its mechanism may be associated with inhibiting microglia-mediated inflammatory response through α7nAChR/NF- κB signaling pathway， thus reducing hippocampal neuronal damage.

Advances in the application of three-dimensional visualization technique in hepatic alveolar echinococcosis / 临床肝胆病杂志

Hepatic alveolar echinococcosis (HAE) is a parasitic disease caused by Echinococcus multilocularis infection and has wide distribution and great harm in China. At present, ultrasound, CT, and MRI are the main radiological examination methods for HAE, with certain limitations in preoperative diagnosis and evaluation. This article introduces the guiding effect of three-dimensional visualization technique and its derivative technologies in the accurate diagnosis and preoperative evaluation of HAE, so as to provide help for the clinical diagnosis and treatment of HAE in the future.

Gut microbiota as a target for traditional Chinese medicine in the treatment of cardiovascular disease: potential mechanisms and therapy strategies / 药学学报

Cardiovascular disease (CVD) is a major contributor to patient deaths worldwide, and its pathogenesis is complex and mortality rates are increasing every year. Numerous researches have shown that the gut microbiota and its metabolites were closely associated with the development of CVD, and gut microbiota was expected to be a potential new target for the treatment of CVD. Traditional Chinese medicine (TCM), characterized by its multi-component, multi-target and integrity, can play a therapeutic role in CVD by regulating the gut microbiota, which has obvious advantages in stabilizing the disease, improving heart function and enhancing quality of life, and is an ideal intestinal microecological regulator. Therefore, this review will mainly discuss the intimate association of gut microbiota and its metabolites with CVD, and the therapeutic strategies of TCM targeting gut microbiota to improve CVD, including regulating the composition of gut microbiota, protecting the intestinal mucosal barrier, influencing the intestinal immune function and modulating the metabolites of gut microbiota, in order to provide a reference for the research of TCM targeting gut microbiota for CVD.

Research hotspots and frontiers of childhood hypertension / 中国学校卫生

Objective@#To analyze the research status, hotspots and frontier progress of hypertension in children in English and Chinese literature, so as to provide reference for the early prevention of hypertension in children.@*Methods@#The Web of Science core collection database and CNKI database were searched to collect the literature related to the study of hypertension in children from 2000 to 2021, and the CiteSpace 5.8.R3 and VOSviewer 1.6.18 visualization tools were used to analyze the literature characteristics including publications, authors, regions, institutional cooperation, research hotspots and frontiers.@*Results@#A total of 22 687 English studies and 4 440 Chinese studies were finally included. According to the analysis results, the number of articles published on hypertension in children was on the rise. The published English articles were mainly University of Toronto and University of Colorado. The main publishing institution of Chinese articles was the First Affiliated Hospital of Peking University. The United States and China took the lead in the number of core journals published in the field of hypertension in children, the United States ranked first in terms of the influence of publications. Keyword co occurrence analysis showed that the high frequency keywords in the English literature included prevalence, risk, obesity, risk factor, body mass index, insulin resistance, overweight, metabolic syndrome, cardiovascular disease and mortality. Chinese high frequency keywords in the literature include obesity, risk factors, adiposis, influencing factors, overweight, prevalence, diabetes, treatment, health education and body mass index. The analysis of keywords showed that 25 burst terms were obtained separately in English and Chinese literature.@*Conclusion@#In recent years, the research interest on hypertension in children continues to grow and keeps updated, with the research scope expanding significantly, regarding obesity, diabetes and cardiovascular diseases.

Clinicopathologic features and prognosis of young renal tumors with tumor thrombus / 北京大学学报(医学版)

OBJECTIVE@#To retrospectively analyze clinical data of patients under 40 years old who underwent surgical treatment for renal tumors with tumor thrombus from January 2016 to December 2022 at Peking University Third Hospital, and to evaluate the surgical effect and investigate the relationship between clinicopathological characteristics and prognosis.@*METHODS@#The clinical data of 17 young patients with renal tumor thrombus were retrospectively analyzed, and the clinicopathological features and prognosis were summarized. The patients were grouped according to the presence or absence of symptoms, 2017 American Joint Committee on Cancer (AJCC) clinical stage, and postoperative combined adjuvant therapy. Kaplan-Meier method was used to plot the survival curve, and Log-rank test was used to compare the differences in postoperative survival time and progression-free survival time between the different groups. The relationship between clinicopathological features and prognosis was analyzed.@*RESULTS@#All the 17 patients received venous tumor thrombectomy, including 16 patients (94.1%) who underwent radical nephrectomy and 1 patient (5.9%) who underwent partial nephrectomy. Twelve patients (70.6%) had symptoms and 5 (29.4%) had no symptoms before operation. A total of 17 renal tumors were observed, with 2 patients (11.8%) identified as benign and 15 patients (88.2%) classified as malignant. Among the malignant tumors, 1 patient (6.7%) was diagnosed as clear cell carcinoma, while the remaining 14 patients (93.3%) were categorized as non-clear cell carcinoma. In terms of tumor stage, 8 patients (53.3%) were classified as stage Ⅲ according to the AJCC classification, while 7 patients (46.7%) were categorized as stage Ⅳ. Additionally, 6 patients (40%) received multiple adjuvant therapy, while 9 patients (60%) did not undergo such treatment. The follow-up period ranged from 2 to 78 months, with a median follow-up of 41 months. During this time, 3 patients (20%) died. The median survival time after surgery was 39.0 (2.3, 77.8) months, and the progression-free survival time was 16.4 (2.3, 77.8) months. There was no significant difference in postoperative survival time and progression-free survival time among young patients with renal tumor with tumor thrombus, based on the presence of symptoms before surgery (P=0.307, P=0.302), clinical stage of AJCC (P=0.340, P=0.492), and postoperative adjuvant therapy (P=0.459, P=0.253) group.@*CONCLUSION@#The pathological types of young patients with renal tumor with tumor thrombus are more complex and varied due to symptoms, and the proportion of non-clear cell carcinoma in malignant tumor with tumor thrombus is higher. Symptomatic and non-clear cell carcinoma may be potentially associated with poor prognosis. Surgical operation combined with adjuvant therapy is a relatively safe and effective treatment for young patients with renal tumor and tumor thrombus.

Predictive model of early urinary continence recovery based on prostate gland MRI parameters after laparoscopic radical prostatectomy / 北京大学学报(医学版)

OBJECTIVE@#Constructing a predictive model for urinary incontinence after laparoscopic radical prostatectomy (LRP) based on prostatic gland related MRI parameters.@*METHODS@#In this study, 202 cases were included. All the patients were diagnosed with prostate cancer by prostate biopsy and underwent LRP surgery in Peking University Third Hospital. The preoperative MRI examination of all the patients was completed within 1 week before the prostate biopsy. Prostatic gland related parameters included prostate length, width, height, prostatic volume, intravesical prostatic protrusion length (IPPL), prostate apex shape, etc. From the first month after the operation, the recovery of urinary continence was followed up every month, and the recovery of urinary continence was based on the need not to use the urine pad all day long. Logistic multivariate regression analysis was used to analyze the influence of early postoperative recovery of urinary continence. Risk factors were used to draw the receiver operator characteristic (ROC) curves of each model to predict the recovery of postoperative urinary continence, and the difference of the area under the curve (AUC) was compared by DeLong test, and the clinical net benefit of the model was evaluated by decision curve analysis (DCA).@*RESULTS@#The average age of 202 patients was 69.0 (64.0, 75.5) years, the average prostate specific antigen (PSA) before puncture was 12.12 (7.36, 20.06) μg/L, and the Gleason score < 7 points and ≥ 7 points were 73 cases (36.2%) and 129 cases (63.9%) respectively, with 100 cases (49.5%) at T1/T2 clinical stage, and 102 cases (50.5%) at T3 stage. The prostatic volume measured by preoperative MRI was 35.4 (26.2, 51.1) mL, the ratio of the height to the width was 0.91 (0.77, 1.07), the membranous urethral length (MUL) was 15 (11, 16) mm, and the IPPL was 2 (0, 6) mm. The prostatic apex A-D subtypes were 67 cases (33.2%), 80 cases (39.6%), 24 cases (11.9%) and 31 cases (15.3%), respectively. The training set and validation set were 141 cases and 61 cases, respectively. The operations of all the patients were successfully completed, and the urinary continence rate was 59.4% (120/202) in the 3 months follow-up. The results of multivariate analysis of the training set showed that the MUL (P < 0.001), IPPL (P=0.017) and clinical stage (P=0.022) were independent risk factors for urinary incontinence in the early postoperative period (3 months). The nomogram and clinical decision curve were made according to the results of multivariate analysis. The AUC value of the training set was 0.885 (0.826, 0.944), and the AUC value of the validation set was 0.854 (0.757, 0.950). In the verification set, the Hosmer-Lemeshow goodness-of-fit test was performed on the model, and the Chi-square value was 5.426 (P=0.711).@*CONCLUSION@#Preoperative MUL, IPPL, and clinical stage are indepen-dent risk factors for incontinence after LRP. The nomogram developed based on the relevant parameters of MRI glands can effectively predict the recovery of early urinary continence after LRP. The results of this study require further large-scale clinical research to confirm.

Risk factors for massive hemorrhage after radical nephrectomy and removal of venous tumor thrombus / 北京大学学报(医学版)

OBJECTIVE@#To investigate and analyze the risk factors of massive hemorrhage in patients with renal cell carcinoma and venous tumor thrombus undergoing radical nephrectomy and removal of venous tumor thrombus.@*METHODS@#From January 2014 to June 2020, 241 patients with renal cancer and tumor thrombus in a single center of urology at Peking University Third Hospital were retrospectively analyzed. All patients underwent radical nephrectomy and removal of venous tumor thrombus. The relevant preoperative indicators, intraoperative conditions, and postoperative data were statistically analyzed by using statistical software of SPSS 18.0. The main end point of the study was intraoperative bleeding volume greater than 2 000 mL. Logistic regression analysis was used to determine the relevant influencing factors. First, single factor Logistic regression was used for preliminary screening of influencing factors, and variables with single factor Logistic regression analysis P < 0.05 were included in multivariate Logistic regression. In all statistical analyses, P < 0.05 is considered statistically significant.@*RESULTS@#Among the 241 patients included, there were 60 cases of massive hemorrhage, 48 males and 12 females, with a median age of 62 years. The number of non-massive hemorrhage was 181. There were 136 males and 45 females, with a median age of 59 years. Univariate analysis showed that the clinical symptoms (both systemic and local symptoms, OR 2.794, 95%CI 1.087-7.181, P=0.033), surgical approach (open surgery, OR 9.365, 95%CI 4.447-19.72, P < 0.001), Mayo grade (Mayo 3-4, OR 5.257, 95%CI 2.806-10.886, P < 0.001), American Society of Anesthesiologists (ASA) score (ASA level 3, OR 2.842, 95%CI 1.338-6.036, P=0.007), preoperative hemoglobin (OR 0.978, 95%CI 0.965-0.991, P=0.001), preoperative platelet count (OR 0.996, 95%CI 0.992-1.000, P=0.037), maximum tumor thrombus width (OR 1.061, 95%CI 1.033-1.091, P < 0.001), Complicated with bland thrombus (OR 4.493, 95%CI 2.264-8.915, P < 0.001), adrenalectomy (OR 3.101, 95%CI 1.614-5.958, P=0.001), segmental resection of the inferior vena cava (OR 2.857, 95%CI 1.395-5.852, P=0.004). There was a statistically significant difference in these aspects(P < 0.05). Multivariate Logistic regression analysis showed that there was a statistically significant difference in surgical approach (open surgery, OR 6.730, 95%CI 2.947-15.368;P < 0.001), Mayo grade (Mayo 3-4, OR 2.294, 95%CI 1.064-4.948, P=0.034), Complicated with bland thrombus (OR 3.236, 95%CI 1.492-7.020, P=0.003).@*CONCLUSION@#Combining the results of univariate and multivariate Logistic regression analysis, the surgical approach, Mayo grade, and tumor thrombus combined with conventional thrombus were associated risk factors for massive hemorrhage during surgery for renal cell carcinoma with tumor thrombus. Patients who undergo open surgery, high Mayo grade, and tumor thrombus combined with conventional thrombus are at a relatively higher risk of massive hemorrhage.

Near-infrared targeted probe designed for intraoperative imaging of prostatic neurovascular bundles / 北京大学学报(医学版)

OBJECTIVE@#To investigate the imaging effect of a near-infrared fluorescent targeted probe ICG-NP41 on the neurovascular bundles (NVB) around the prostate in rats.@*METHODS@#A near-infrared fluorescent targeted probe ICG-NP41 was synthesized. An animal model for NVB imaging was established using Sprague-Dawley rats (250-400 g). Experiments were conducted using a custom-built near-infrared windowⅡ(NIR-Ⅱ) small animal in vivo imaging system, and images collected were processed using ImageJ and Origin. The fluorescence signal data were statistically analyzed using GraphPad Prism. The signal-to-background ratio (SBR) for NVB was quantitatively calculated to explore the effective dosage and imaging time points. Finally, paraffin pathology sections and HE staining were performed on the imaging structures.@*RESULTS@#Except for rats in the control group (n=2), right-sided NVB of the rats injected with ICG-NP41 (n=2 per group) were all observed in NIR-Ⅱ fluorescence mode 2 h and 4 h after administration. At 2 h and 4 h, average SBR of cavernous nerve in 2 mg/kg group in fluorescence mode was 1.651±0.142 and 1.619±0.110, respectively, both higher than that in white light mode (1.111±0.036), with no significant difference (P>0.05); average SBR of 4 mg/kg group in fluorescence mode were 1.168±0.066 and 1.219±0.118, respectively, both higher than that in white light mode (1.081±0.040), with no significant difference (P>0.05). At 2 h and 4 h, the average SBR of 2 mg/kg and 4 mg/kg groups in fluorescence mode were higher than that of the control group (SBR=1), the average SBR of the 2 mg/kg group was higher than that of the 4 mg/kg group, and all the above with no significant difference (P>0.05). The average diameter of the nerve measured by full width at half maxima method was about (178±15) μm. HE staining of paraffin sections showed the right major pelvic ganglion.@*CONCLUSION@#The near-infrared fluorescent targeted probe ICG-NP41 can be used for real-time imaging of the NVB around the prostate in rats, providing a potential feasible solution for localizing NVB in real time during nerve-sparing radical prostatectomy.

Effects of low centrifugal force on sperm morphology of normal and non-liquefied semen samples / 临床检验杂志

Objective To explore the effects of low centrifugal force on sperm morphology analysis of normal and non-liquefied semen samples.Methods A total of 169 patients who underwent semen routine examination and sperm morphology analysis at the Reproduc-tive Center of the 904th Hospital of the Joint Logistics Support Force of PLA from January 2021 to December 2021 were collected as the study subjects.Among them,126 were the patients with normal semen routine parameters,and 43 with non-liquefied semen.The mor-phological analysis results of 126 normal semen samples treated by the direct smear method and centrifugation methods under two differ-ent of low centrifugal force were compared.The results of morphological analysis for the 43 non-liquefied semen samples treated by the direct smear method after promoting liquefaction and centrifugation were compared.Results The percentage of normal morphological sperm[(9.39±0.50)％]obtained by centrifugation of 340xg centrifugal force for 10 min was significantly lower than that[(11.08± 0.41)％]obtained by the direct smear method,and the abnormal rate of sperm in the middle segment[(62.05±1.44)％]obtained by centrifugation of 340xg centrifugal force was significantly higher than that[(57.17±0.82)％]obtained by the direct smear method.The percentage of normal morphological sperm[(9.41±0.57)％]obtained by centrifugation at 151×g centrifugal force was significantly lower than that obtained by the direct smear method,and the abnormal rate of sperm in the middle segment[(60.95±1.17)％]ob-tained by centrifugation at 151×g centrifugal force was significantly higher than that obtained by the direct smear method.For non-lique-fied semen samples,the percentage of normal morphological sperm obtained by centrifugation at 340xg centrifugal force for 10 min was[(9.61±0.60)％],while that obtained by the direct smear method after promoting liquefaction was[(11.10±0.73)％].The difference was not statistically significant between the two methods.The abnormal rate of sperm in the middle segment[(60.21±1.51)％]ob-tained by the centrifugation method was also not significantly different from that[(57.36±1.34)％]obtained by the direct smear meth-od after promoting liquefaction.Conclusion Both kinds of low centrifugal force affected the sperm morphology.However,the low cen-trifugal force has no significant effect on the non-liquefied semen.In the clinical application of sperm morphology analysis,the nature of male semen should be referred to determine whether the centrifugation is need or not and the magnitude of centrifugal force.

Influencing factors of textbook outcomes in liver surgery after radical resection of gallbladder carcinoma: a national multicenter study / 中华消化外科杂志

Objective:To investigate the influencing factors of textbook outcomes in liver surgery (TOLS) after radical resection of gallbladder carcinoma.Methods:The retrospective case-control study was conducted. The clinicopathological data of 530 patients who underwent radical resection of gallbladder carcinoma in 15 medical centers, including the First Affiliated Hospital of Army Medical University et al, from January 2014 to January 2020 were collected. There were 209 males and 321 females, aged (61±10)years. Patients underwent radical resection of gallbladder carcinoma, including cholecystectomy, hepatectomy, invasive bile duct resection, and lymph node dissection. Observation indicators: (1) situations of TOLS; (2) influencing factors of TOLS. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. The univariate analysis was conducted using the corresponding statistical methods based on data type, and variables with P<0.10 were included in multivariate analysis. Multivariate analysis was conducted using the Logistic stepwise regression model. Results:(1) Situations of TOLS. All 530 patients underwent radical resection of gallbladder carcinoma, and there were 498 cases achieving R 0 resection, 508 cases without ≥grade 2 intra-operative adverse events, 456 cases without postoperative grade B and grade C biliary leakage, 513 cases without postoperative grade B and grade C liver failure, 395 cases without severe com-plications within postoperative 90 days, 501 cases did not being re-admission caused by severe com-plications within postoperative 90 days. Of the 530 patients, 54.53%(289/530) of patients achieved postoperative TOLS, while 45.47%(241/530) of patients did not achieve postoperative TOLS. (2) Influencing factors of TOLS. Results of multivariate analysis showed that American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy were independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma ( odds ratio=2.65, 1.87, 5.67, 5.65, 2.55, 3.34, 95% confidence interval as 1.22?5.72, 1.18?2.95, 2.51?12.82, 2.83?11.27, 1.41?4.63, 1.88?5.92, P<0.05). Conclusion:American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy are independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma.

Research progress of perineural invasion in gallbladder cancer / 中华消化外科杂志

As a special mode of tumor metastasis, perineural invasion has been paid more and more attention. It is closely related to prognosis, recurrence and metastasis of tumor after surgery. As the most common malignancy of the biliary tract, perineural invasion is also an inde-pendent prognostic risk factor for gallbladder cancer due to its anatomical location, lymphatic reflux, blood perfusion and innervation. However, there are few studies on perineural invasion in gallbla-dder cancer, especially on its mechanism. By analyzing the general situation and recent progress of perineural invasion in gallbladder cancer, the authors mainly introduce the perineural invasion mechanism, perineural invasion rate of gallbladder cancer, relationship between perineural invasion and the clinical pathologic characteristic, the correlation with the prognosis, relationship with surgi-cal procedures and postoperative adjuvant therapy.

Predictive value of anticardiolipin antibody and D-dimer combined with risk assessment profile for thromboembolism for deep vein thrombosis in elderly postoperative patients with intertrochanteric fracture of femur / 中国医师进修杂志

Objective:To investigate the predictive value of anticardiolipin antibody (ACA) and D-dimer (D-D) combined with risk assessment profile for thromboembolism (RAPT) for deep vein thrombosis (DVT) in elderly postoperative patients with intertrochanteric fracture of femur (IFF).Methods:The clinical data of 123 elderly patients with IFF in Suzhou Hospital Affiliated to Anhui Medical University from January 2019 to March 2022 were retrospectively analyzed. All patients underwent closed reduction intramedullary nail fixation. The patients were divided into DVT group (27 cases) and non-DVT group (96 cases) according to the presence or absence of DVT 7 d after surgery. Before surgery and 3, 5 d after operation, the ACA was detected by enzyme-linked immunosorbent assay, the D-D was detected by automatic coagulation analyzer, and RAPT was performed. The correlation among ACA, D-D and RAPT was analyzed by Spearman method. Multivariate Logistic regression was used to analyze the independent risk factors of DVT in elderly postoperative patients with IFF. Receiver operating characteristic (ROC) curve was used to analyze the efficacy of ACA, D-D and RAPT in predicting DVT in elderly postoperative patients with IFF. The incidences of postoperative DVT in patients with different ACA, D-D and RAPT patients were compared.Results:There were no statistical difference in ACA, D-D and RAPT before operation between the two groups ( P>0.05); the ACA, D-D and RAPT 3 and 5 d after operation in DVT group were significantly higher than those in the non-DVT group, 3 d after operation: (12.44 ± 3.25) × 10 3 RU/L vs. (8.67 ± 2.81) × 10 3 RU/L, (7.29 ± 1.49) mg/L vs. (4.70 ± 1.23) mg/L and (9.79 ± 1.15) scores vs. (9.21 ± 1.32) scores; 5 d after operation: (10.28 ± 2.16) × 10 3 RU/L vs. (6.45 ± 2.04) × 10 3 RU/L, (5.49 ± 1.26) mg/L vs. (3.63 ± 1.05) mg/L and (9.57 ± 1.08) scores vs. (9.12 ± 0.70) scores, and there were statistical differences ( P<0.01 or <0.05). Since ACA, D-D and RAPT in the two groups all reached their peak 3 d after operation, this time point was selected for analysis. Three days after operation, Pearson correlation analysis result showed that ACA and D-D were positively correlated with RAPT ( r = 0.635 and 0.630, P<0.01), and ACA was positively correlated with D-D ( r = 0.657, P<0.01). ROC curve analysis result showed that the area under the curve (AUC) of ACA and D-D combined RAPT 3 d after operation in predicting DVT in elderly postoperative patients with IFF was greater than that predicted by the 3 indexes alone (0.982 vs. 0.894, 0.870 and 0.868), the optimal cut-off values were 11.48 × 10 3 RU/L, 6.75 mg/L and 9 scores. According to the optimal cut-off value of ROC curve analysis at 3 d after operation, the patients were divided into ACA low expression (≤11.48 × 10 3 RU/L, 92 cases) and ACA high expression (>11.48 × 10 3 RU/L, 31 cases), D-D low expression (≤6.75 mg/L, 99 cases) and D-D high expression (>6.75 mg/L, 24 cases), low RAPT (≤9 scores, 93 cases) and high RAPT (>9 scores, 30 cases). The incidences of postoperative DVT in patients with ACA high expression, D-D high expression and high RAPT were significantly higher than those in patients with ACA low expression, D-D low expression and low RAPT: 43.39% (15/31) vs. 13.04% (12/92), 54.17% (13/24) vs. 14.14% (14/99) and 53.33% (16/30) vs. 11.83% (11/93), and there were statistical differences ( χ2 = 16.91, 18.06 and 22.81; P<0.01). After controlling for diabetes and other factors, multivariate Logistic regression analysis result showed that ACA, D-D and RAPT 3 d after operation were independent risk factors for DVT in elderly postoperative patients with IFF ( OR = 2.156, 2.276 and 6.106; 95% CI 1.356 to 3.429, 1.240 to 4.177 and 1.564 to 23.840; P<0.01). Conclusions:The ACA, D-D combined with RAPT can improve the predictive value of DVT in elderly postoperative patients with IFF, which has important reference significance for taking timely and effective intervention measures in early clinical stage.

Structure-based drug discovery of novel fused-pyrazolone carboxamide derivatives as potent and selective AXL inhibitors

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC50: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC50: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.

Analysis of prognostic factors of extranodal NK/T-cell lymphoma treated with pegaspargase/L-asparaginase: a multicenter retrospective study / 中华血液学杂志

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.