Comparison of prediction ability of two extended Cox models in nonlinear survival data analysis / 南方医科大学学报

OBJECTIVE@#To compare the predictive ability of two extended Cox models in nonlinear survival data analysis.@*METHODS@#Through Monte Carlo simulation and empirical study and with the conventional Cox Proportional Hazards model and Random Survival Forests as the reference models, we compared restricted cubic spline Cox model (Cox_RCS) and DeepSurv neural network Cox model (Cox_DNN) for their prediction ability in nonlinear survival data analysis. Concordance index was used to evaluate the differentiation of the prediction results (a larger concordance index indicates a better prediction ability of the model). Integrated Brier Score was used to evaluate the calibration degree of the prediction (a smaller index indicates a better prediction ability).@*RESULTS@#For data that met requirement of the proportion risk, the Cox_RCS model had the best prediction ability regardless of the sample size or deletion rate. For data that failed to meet the proportion risk, the prediction ability of Cox_DNN was optimal for a large sample size (≥500) with a low deletion (< 40%); the prediction ability of Cox_RCS was superior to those of other models in all other scenarios. For example data, the Cox_RCS model showed the best performance.@*CONCLUSION@#In analysis of nonlinear low maintenance data, Cox_RCS and Cox_DNN have their respective advantages and disadvantages in prediction. The conventional survival analysis methods are not inferior to machine learning or deep learning methods under certain conditions.

Current status of diagnosis and treatment of chronic lymphocytic leukemia in China: A national multicenter survey research / 中华血液学杂志

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.

Factors influencing severe cytopenia in chronic phase chronic myeloid leukemia patients receiving initial second generation tyrosine kinase inhibitors and its impact on treatment responses and outcomes / 中华血液学杂志

Objective: To explore the influencing covariates of severe neutrophils and/or thrombocytopenia and their effect on treatment response and outcome in patients with chronic-phase chronic myeloid leukemia (CP-CML) receiving initial second-generation tyrosine kinase inhibitors (2G-TKI) . Methods: Data from consecutive patients aged ≥18 years with newly diagnosed CP-CML who received initial 2G-TKI at Peking University People's Hospital from September 2008 to November 2021 were interrogated. Binary logistic regression models and Fine-Gray and Cox regression models were applied. Results: Data from 267 patients who received initial 2G-TKI, including nilotinib (n=239, 89.5% ) and dasatinib (n=28, 10.5% ) , were interrogated. The median age was 36 (range, 18-73) years, and 156 (58.4% ) patients were male. At a median treatment period of 1.0 (0.1-3.0) month, 43 (16.1% ) patients developed grade ≥3 neutrophils and/or thrombocytopenia and recovered within 1.0 (0.1-24.6) month. Male (OR=2.9, 95% CI 1.2-6.8; P=0.018) , age of ≥36 years (OR=3.2, 95% CI 1.4-7.2, P=0.005) , a spleen below a costal margin of ≥7 cm (OR=2.8, 95% CI 1.2-6.6, P=0.020) , and a hemoglobin (HGB) level of <100 g/L (OR=2.9, 95% CI 1.3-6.8, P=0.012) at diagnosis were significantly associated with grade ≥ 3 neutrophils and/or thrombocytopenia. Based on their regression coefficients, male, age of ≥36 years, a spleen below a costal margin of ≥7 cm, and an HGB level of <100 g/L were given 1 point to form a predictive system. All patients were divided into three risk subgroups, and the incidence of severe cytopenia significantly differed among the three groups (P < 0.001) . Grade ≥3 neutrophils and/or thrombocytopenia for >2 weeks was significantly associated with lower cumulative incidences of complete cytogenetic response (CCyR, HR=0.5, 95% CI 0.3-0.7, P<0.001) and major molecular response (MMR, HR=0.4, 95% CI 0.3-0.8, P=0.004) and was not significantly associated with failure, progression, and survival. Conclusion: Male, advanced age, a large spleen, and a low HGB level were significantly associated with severe cytopenia. The four covariates were used to establish a prediction model, in which the incidence of severe cytopenia among different risk groups was significantly different. Severe cytopenia for >2 weeks was a negative factor for responses but not for outcomes.

Research Progress of Age Estimation in the Living by Knee Joint MRI / 法医学杂志

Bone development shows certain regularity with age. The regularity can be used to infer age and serve many fields such as justice, medicine, archaeology, etc. As a non-invasive evaluation method of the epiphyseal development stage, MRI is widely used in living age estimation. In recent years, the rapid development of machine learning has significantly improved the effectiveness and reliability of living age estimation, which is one of the main development directions of current research. This paper summarizes the analysis methods of age estimation by knee joint MRI, introduces the current research trends, and future application trend.

Antibacterial copper sulfide/graphene oxide nanosheets composite film promotes angiogenic and osteogenic differentiation in vitro / 中华创伤骨科杂志

Objective:To investigate whether the antibacterial copper sulfide (CuS)/graphene oxide (GO) nanosheets composite film can promote angiogenesis and osteogenesis in vitro. Methods:GO and CuS/GO nanosheets were synthesized and mixed into polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC) hydrogel films. The study was conducted in 4 groups: PVA/CMC/GO, PVA/CMC/CuS/GO, PVA/CMC (only PVA/CMC-based film) and blank control (no material). The PVA/CMC, PVA/CMC/GO and PVA/CMC/CuS/GO films were characterized by electron scanning microscopy and energy dispersive spectrometer. The biocompatibility of different films (PVA/CMC/CuS/GO films with concentrations of CuS/GO nanotablets of 0, 50, 100, 200, 400, and 800 μ g/mL) was evaluated by CCK-8, live/dead cell staining, and hemolysis test. The angiogenesis was evaluated by cell migration and tube forming test in vitro. Alkaline phosphatase and alizarin red staining were used to evaluate osteogenesis in vitro, and the expression of osteogenic genes was measured by immunofluorescence staining and RT-qPCR. In addition, the bacterial plate counting method and bacteriostatic circle method were used to evaluate the antibacterial activity of films. Results:In the PVA/CMC/GO and PVA/CMC/CuS/GO groups, the surface of the PVA/CMC-based film was smooth and flat whereas the nanosheets composite films were irregularly flaky and convex. The biosafety experiments showed that the PVA/CMC-based film composited with GO or CuS/GO nanosheets at the concentration of 100 μg/mL had good biocompatibility. The results of angiogenesis in vitro showed that the migration ratio of HUVEC cells in the PVA/CMC/CuS/GO group was significantly better than those in the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). In the experiment of tube forming area and length, the PVA/CMC/CuS/GO group was significantly better than the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). The osteogenic differentiation in vitro displayed that the alkaline phosphatase and alizarin red staining of MC3T3-E1 cells in the PVA/CMC/CuS/GO group were significantly better than those in the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). In addition, the fluorescence intensity of immunofluorescence staining in alkaline phosphatase and type Ⅰcollagen on MC3T3-E1 cells, and the mRNA expression levels of osteogenic related genes including alkaline phosphatase, bone morphogenetic protein 2, osteocalcin and osteopontin in the PVA/CMC/CuS/GO group were significantly higher than those in the PVA/CMC/GO, PVA/CMC and control groups ( P<0.001). The antibacterial assay showed that the PVA/CMC/CuS/GO group had a significantly greater antibacterial activity and a significantly larger inhibition zone against Gram-positive bacteria and Gram-negative bacteria than the PVA/CMC/GO, PVA/CMC and control groups ( P< 0.001). Conclusions:PVA/CMC films composited with GO or CuS/GO nanosheets demonstrate ideal biocompatibility and antibacterial properties which promote angiogenesis and osteogenic differentiation in vitro. In particular, antibacterial PVA/CMC/CuS/GO composite films with the coupling function of angiogenesis and osteogenesis are expected to provide a new strategy for infectious bone defects.

Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults (version 2023) / 中华创伤杂志

The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.

Clinical guideline for diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture (version 2023) / 中华创伤杂志

Ankylosing spondylitis (AS) combined with spinal fractures with thoracic and lumbar fracture as the most common type shows characteristics of unstable fracture, high incidence of nerve injury, high mortality and high disability rate. The diagnosis may be missed because it is mostly caused by low-energy injury, when spinal rigidity and osteoporosis have a great impact on the accuracy of imaging examination. At the same time, the treatment choices are controversial, with no relevant specifications. Non-operative treatments can easily lead to bone nonunion, pseudoarthrosis and delayed nerve injury, while surgeries may be failed due to internal fixation failure. At present, there are no evidence-based guidelines for the diagnosis and treatment of AS combined with thoracic and lumbar fracture. In this context, the Spinal Trauma Academic Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate the Clinical guideline for the diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture ( version 2023) by following the principles of evidence-based medicine and systematically review related literatures. Ten recommendations on the diagnosis, imaging evaluation, classification and treatment of AS combined with thoracic and lumbar fracture were put forward, aiming to standardize the clinical diagnosis and treatment of such disorder.

Subclassification and clinical treatment options of refractory atlantoaxial dislocation / 中华骨科杂志

Objective:To subdivide clinical classification of refractory atlantoaxial dislocation, and evaluate the reliability of new subdivide clinical classification of refractory atlantoaxial dislocation.Methods:From January 2010 to December 2018, 48 patients with refractory atlantoaxial dislocation were treated, including 19 males and 29 females, aged 16 to 65 years, with an average of 39.2±13.3 years. According to the changes of relative anatomical position of C 1 and C 2 under general anesthesia with heavy traction of 1/6 body weight, subdivide clinical classification of refractory atlantoaxial dislocation were proposed, and refractory atlantoaxial dislocation was divided into traction loosening type (atlantoaxial angle≥5°) and traction stabilization type (atlantoaxial angle<5°). The traction loosening type was directly reduced by posterior atlantoaxial screw-rod fixation and fusion without anterior or posterior soft tissue release. For traction stabilization type, transoral soft tissue release was performed first, and then transoral anterior reduction plate fixation and fusion or posterior atlantoaxial screw-rod fixation and fusion were performed. Atlantodental interval (ADI) and atlantoaxial angle (AAA) were measured and collected before and after surgery to evaluate atlantoaxial reduction. The space available for the spinal cord (SAC) were measured to evaluate spinal cord compression. Visual analogue score (VAS) was used to evaluate the neck pain levels, and Japanese Orthopaedic Association (JOA) scores was used to evaluate the neurological function. American Spinal Cord Injury Association impairment scale (AIS) was used to evaluate the degree of spinal cord injury. One week, 3, 6, 12 months postoperatively and the annual review of the X-ray and CT scan were checked, in order to evaluate the reduction, internal fixation and bone graft fusion. Results:Among all 48 cases, 22 cases were traction loosening type, of which posterior atlantoaxial screw-rod fixation and fusion were performed in 16 cases and occipitocervical fixation and fusion in 6 cases. 26 cases were traction stabilization type, and they all underwent anterior transoral release, and then, anterior TARP fixation and fusion were performed in 24 cases and posterior screw-rod fixation and fusion in the other 2 cases. X-ray, CT and MRI images and of all patients 1 week after surgery showed good atlantoaxial reduction and decompression of spinal cord. In each of the two types, there was one case lost to follow-up. For 46 cases in follow-up, the follow-up time ranged from 6 to 72 months, with an average of 38.0±17.2 months. Among 46 cases, 21 cases of traction loosening type showed that, ADI reduced from preoperative 9.9±2.2 mm to 2.3±0.9 mm at 3 months after surgery and 2.3±1.0 mm at the last follow-up, AAA increased from preoperative 57.9°±12.3° to 91.0°±2.2° at 3 months after surgery and 90.9°±2.2° at the last follow-up, SAC increased from preoperative 9.8±1.3 mm to 15.1±0.7 mm at 3 months after surgery and 14.9±0.7 mm at the last follow-up, VAS score reduced from preoperative 1.5±2.1 to 0.7±1.0 at 3 months after surgery and 0.3±0.6 at the last follow-up, and JOA score increased from preoperative 10.2±1.7 to 13.3±1.3 at 3 months after surgery and 14.9±1.5 at the last follow-up. Twenty-five cases of traction stabilization type presented that, ADI reduced from preoperative 9.7±2.0 mm to 2.1±1.4 mm at 3 months after surgery and 2.1±1.3 mm at the last follow-up, AAA increased from preoperative 55.8°±9.2° to 90.9°±1.4° at 3 months after surgery and 90.9°±1.3° at the last follow-up, SAC increased from preoperative 10.5±1.0 mm to 15.4±0.5 mm at 3 months after surgery and 14.8±2.8 mm at the last follow-up, VAS score reduced from preoperative 1.7±2.1 to 0.7±0.9 at 3 months after surgery and 0.3±0.5 at the last follow-up, and JOA score increased from preoperative 10.1±1.3 to 12.9±1.5 at 3 months after surgery and 14.4±1.3 at the last follow-up. In the traction loosening type, all the 10 grade D patients were improved to grade E at the last follow-up. In the 2 grade C patients of traction stabilization type before surgery, 1 patient was improved to grade E, 1 patient was improved to grade D, and all 11 patients with grade D were improved to grade E at the last follow-up. Bony fusion was obtained in all patients from 3 to 6 months, with an average of 4.4±1.5 months. During follow-up period, no looseness of internal fixation or redislocation happened.Conclusion:Refractory atlantoaxial dislocation can be divided into traction loosening type and traction stabilization type. For traction loosening type, satisfactory reduction can be achieved by using posterior atlantoaxial screw-rod system without soft tissue release. For traction stabilization type, anterior release is preferable, and then anterior TARP or posterior screw-rod can be used to achieve satisfactory reduction.

Spatial-temporal distribution of pulmonary tuberculosis registered in Fuling District of Chongqing during the 13th Five-Year Plan period / 中国热带医学

@#Abstract: Objective To analyze the spatial-temporal characteristics of the active pulmonary tuberculosis (PTB) and the pathogenic positive PTB in Fuling District of Chongqing during the 13th Five-Year Plan period, so as to explore the clustering areas, and provide scientific basis for the precise prevention and control of tuberculosis in Fuling District. Methods The PTB registration data of 27 townships in Fuling District from 2016 to 2020 were collected. The descriptive analysis were used to describe the temporal and spatial distribution characteristics of patients, SaTScan9.0 and ArcGis10.6 was used for spatial-temporal scanning analysis and local auto-correlation analysis. The results were visualized by ArcGis10.6. Results A total of 4 038 case of active PTB patients were registered and a downward trend was observed in PTB during the 13th Five-Year Plan period in Fuling District. The average annual registration rate of PTB was 70.17/100 000, and the annual PTB registration rate declined by 8.21%. The peak of active PTB and etiological positive PTB were mainly concentrated in March and June respectively. The top five streets of cumulative active PTB patients registered were Lizhi street, Dunren street, Chongyi street, Ma 'an street and Jiangdong street, accounting for 60.18% of the total registered PTB patients during the 13th Five-Year Plan period. The top three average annual registration rates were Dunren street (101.35/100 000), Chongyi street (101.34/100 000) and Wulingshan Township (99.21/100 000). The registered PTB from 2016 to 2020 showed a global auto-correlation (Moran's I=0.64, P<0.0001). The "high-high" area of active PTB and the etiological positive PTB all covered Lizhi street, Jiangdong street and Longqiao street. By scanning analysis of spatial-temporal, the primary cluster of active PTB concentrated in the main urban area south of the Yangtze River in Fuling during January 2016 to December 2017, and the primary cluster of pathogenic positive PTB concentrated in the main urban area south of the Yangtze River in Fuling and Jiangdong street during January 2019 to December 2020. Conclusions During the 13th Five-Year Plan period, there was the spatial-temporal clustering of PTB in Fuling District, which mainly gathered in the main urban area south of the Yangtze River in Fuling district and surrounding streets centered on Lizhi street.

Deubiquitinating enzyme MINDY1 is an independent risk factor for the maintenance of stemness and poor prognosis in liver cancer cells / 中华肝脏病杂志

Objective: To explore the key deubiquitinating enzymes that maintain the stemness of liver cancer stem cells and provide new ideas for targeted liver cancer therapy. Methods: The high-throughput CRISPR screening technology was used to screen the deubiquitinating enzymes that maintain the stemness of liver cancer stem cells. RT-qPCR and Western blot were used to analyze gene expression levels. Stemness of liver cancer cells was detected by spheroid-formation and soft agar colony formation assays. Tumor growth in nude mice was detected by subcutaneous tumor-bearing experiments. Bioinformatics and clinical samples were examined for the clinical significance of target genes. Results: MINDY1 was highly expressed in liver cancer stem cells. The expression of stem markers, the self-renewal ability of cells, and the growth of transplanted tumors were significantly reduced and inhibited after knocking out MINDY1, and its mechanism of action may be related to the regulation of the Wnt signaling pathway. The expression level of MINDY1 was higher in liver cancer tissues than that in adjacent tumors, which was closely related to tumor progression, and its high expression was an independent risk factor for a poor prognosis of liver cancer. Conclusion: The deubiquitinating enzyme MINDY1 promotes stemness in liver cancer cells and is one of the independent predictors of poor prognosis in liver cancer.

Relationship between cadmium exposure and pulmonary function level and chronic obstructive pulmonary disease / 中华劳动卫生职业病杂志

Objective: To analyze the levels and distribution characteristics of blood cadmium and urinary cadmium in American adults, to analyze the relationship between blood cadmium and urinary cadmium and pulmonary function dose response, and to explore the effect of this index on the risk of chronic obstructive pulmonary disease. Methods: In March 2022, 3785 patients from 2007 to 2012 in NHANES database were selected as the subjects. Collect demography data such as gender and age, and test data such as lung function, blood cadmium concentration and Urine cadimium concentration. The relationship between blood and urine cadmium levels and lung function and pulmonary function and chronic obstructive pulmonary diease (COPD) was analyzed by Mann-Whitney U test or Kruskal-Wallis H test, multivariate linear regression and restricted cubic spline method. Results: The geometric mean of blood cadmium and urine cadmium in American adults was 0.37 g/L and 0.28 g/L, FEV(1) and FEV(1)/FVC among different cadmium exposure groups was statistically significant, and there was a negative linear dose-response relationship between serum Cd and urine Cd concentrations and FEV(1)/FVC levels (P(overall)<0.001, P(non-linear)=0.152; P(overall)<0.001, P(non-linear)=0.926). Compared with the lowest quartile concentration (Q1), the highest quartile blood cadmium concentration (Q4) (OR=1.934, P(trend)=0.000) and urinary cadmium concentration (OR=1.683, P(trend)=0.000) may increased the risk of chronic obstructive pulmonary disease. Conclusion: There is a negative correlation between blood cadmium, urinary cadmium levels and lung function in American adults, and cadmium may increase the risk of chronic obstructive pulmonary disease.

Efficacy of high-dose dual therapy for Helicobacter pylori infection eradication in servicemen: a randomized controlled trial / 中华内科杂志

Objective: To assess the efficacy and cost-effectiveness of high-dose dual therapy compared with bismuth-containing quadruple therapy for treating Helicobacter pylori(H.pylori) infection in servicemen patients. Methods: A total of 160 H. pylori-infected, treatment-naive servicemen, including 74 men and 86 women, aged from 20 years to 74 years, with a mean (SD) age of 43 (13) years, tested in the First Center of Chinese PLA General Hospital from March 2022 to May 2022 were enrolled in this open-label, randomized controlled clinical trial. Patients were randomly allocated into 2 groups: the 14-day high-dose dual therapy group and the bismuth-containing quadruple therapy group. Eradication rates, adverse events, patient compliance, and drug costs were compared between the two groups. The t-test was used for continuous variables, and the Chi-square test for categorical variables. Results: No significant difference in H. pylori eradication rates were found between high-dose dual therapy and bismuth-containing quadruple therapy by ITT, mITT and PP analysis[ITT:90.0% (95%CI 81.2%-95.6%) vs. 87.5% (95%CI 78.2%-93.8%), χ2=0.25, P=0.617;mITT:93.5% (95%CI 85.5%-97.9%) vs. 93.3% (95%CI 85.1%-97.8%), χ2<0.01, P=1.000; PP: 93.5% (95%CI 85.5%-97.9%) vs. 94.5% (95%CI 86.6%-98.5%), χ2<0.01, P=1.000 ]. The dual therapy group exhibited significantly less overall side effects compared with the quadruple therapy group [21.8% (17/78) vs. 38.5% (30/78), χ2=5.15,P=0.023]. There were no significant differences in the compliance rates between the two groups [98.7%(77/78) vs. 94.9%(74/78), χ2=0.83,P=0.363]. The cost of medications in the dual therapy was 32.0% lower compared with that in the quadruple therapy (472.10 RMB vs. 693.94 RMB). Conclusions: The dual regimen has a favorable effect on the eradication of H. pylori infection in servicemen patients. Based on the ITT analysis, the eradication rate of the dual regimen is grade B (90%, good). Additionally, it exhibited a lower incidence of adverse events, better compliance and significantly reduced cost. The dual regimen is expected to be a new choice for the first-line treatment of H. pylori infection in servicemen but needs further evaluation.

Value of ocular trauma score and ocular structural parameters in the assessment of healing visual acuity from ocular trauma / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the value of ocular trauma score(OTS), initial visual acuity, and ocular structural parameters in the assessment of healing visual acuity from ocular trauma.METHOD: A total of 302 cases(302 eyes)of ocular trauma were selected as subjects, which were accepted and issued clear appraisal opinions by the Academy of Forensic Science from June 2015 to June 2021. The subjects were grouped according to the healing best corrected visual acuity(BCVA)from ocular trauma. Group Ⅰ included 63 cases(63 eyes)with BCVA &#x0026;#x003C;3.7; Group Ⅱ included 70 cases(70 eyes)with 3.7≤ BCVA &#x0026;#x003C;4.5; Group Ⅲ included 78 cases(78 eyes)with 4.5≤ BCVA &#x0026;#x003C;4.9; Group Ⅳ included 91 cases(91 eyes)with BCVA≥4.9. In addition, 77 cases(77 healthy eyes)of ocular trauma were selected as the control group, namely Group Ⅴ. The healing BCVA and ocular structural parameters from ocular trauma and theirs correlation were analyzed, and the random forest(RF)and support vector machine(SVM)model of healing visual acuity was established by the IBM SPSS Modeler 18.0.RESULTS: The initial visual acuity, OTS, the grading of corneas, lenses, and fundus, and the thickness of the retinal never fiber layer of ocular trauma patients were correlated with the healing BCVA(P&#x0026;#x003C;0.01). There were significant differences in ocular structural parameters among groups, except the central subfield thickness(P&#x0026;#x003C;0.001). The SVM model had higher accuracy of predicting healing visual acuity than the RF model, and the accuracy rate was over 80% when the error was within 0.15.CONCLUSION:OTS and ocular structural examination can provide effective information for the clinical forensic medicine appraisal of visual dysfunction after ocular trauma, and they are valuable in discriminating camouflage of visual dysfunction.

Factors associated with readmission within three months of surgery for gastric cancer and their long-term effects on patients' nutritional status and quality of life / 中华胃肠外科杂志

Objective: To analyze the factors associated with readmission within three months of surgery for gastric cancer and the impact of readmission on patients' long-term nutritional status and quality of life. Methods: This was a prospective cohort study comprising patients who underwent radical gastrectomy in the Department of Pancreatic and Gastric Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences from October 2018 to August 2019. Patients who failed to complete postoperative follow-up, whose body mass index (BMI) could not be accurately estimated, or who were unable to complete a quality-of-life questionnaire were excluded. The patients were followed up for 12 months. Time to, cause(s) of, and outcomes of readmission were followed up 1, 2 and 3 months postoperatively. BMI was followed up 1, 3, 6 and 12 months postoperatively. Results of blood tests were collected and patients' nutritional status and quality of life were assessed 12 months postoperatively. Nutritional status was evaluated by BMI, hemoglobin, albumin, and total lymphocyte count. Quality of life was evaluated using the European Organization for Research in the Treatment of Cancer (EORTC) Quality of Life scale. The higher the scores for global health and functional domains, the better the quality of life, whereas the higher the score in the symptom domain, the worse the quality of life. Results: The study cohort comprised 259 patients with gastric cancer, all of whom were followed up for 3 months and 236 of whom were followed up for 12 months. Forty-four (17.0%) patients were readmitted within 3 months. The commonest reasons for readmission were gastrointestinal dysfunction (16 cases, 36.3%), intestinal obstruction (8 cases, 18.2%), and anastomotic stenosis (8 cases, 18.2%). Logistic regression analysis showed that preoperative Patient-Generated Subjective Global Assessment score ≥ 4 points (OR=1.481, 95% CI: 1.028‒2.132), postoperative complications (OR=3.298, 95%CI:1.416‒7.684) and resection range (OR=1.582, 95% CI:1.057‒2.369) were risk factors for readmission within 3 months of surgery. Compared with patients who had not been readmitted 12 months after surgery, patients who were readmitted within 3 months of surgery tended to have greater decreases in their BMI [-2.36 (-5.13,-0.42) kg/m2 vs. -1.73 (-3.33,-0.33) kg/m2, Z=1.850, P=0.065), significantly lower hemoglobin and albumin concentrations [(122.1±16.6) g/L vs. (129.8±18.4) g/L, t=2.400, P=0.017]; [(40.9±5.0) g/L vs. (43.4±3.3) g/L, t=3.950, P<0.001], and significantly decreased global health scores in the quality of life assessment [83 (67, 100) vs. 100 (83, 100), Z=2.890,P=0.004]. Conclusion: Preoperative nutritional risk, total or proximal radical gastrectomy, and complications during hospitalization are risk factors for readmission within 3 months of surgery for gastric cancer. Perioperative management and postoperative follow-up should be more rigorous. Readmission within 3 months after surgery may be associated with a decline in long-term nutritional status and quality of life. Achieving improvement in long-term nutritional status and quality of life requires tracking of nutritional status, timely evaluation, and appropriate interventions in patients who need readmission.

Contamination status and exposure risk of mycotoxins in Coicis Semen / 中国中药杂志

By investigating the contamination status and predicting the exposure risk of mycotoxin in Coicis Semen, we aim to provide guidance for the safety supervision of Chinese medicinal materials and the formulation(revision) of mycotoxin limit standards. The content of 14 mycotoxins in the 100 Coicis Semen samples collected from five major markets of Chinese medicinal materials in China was determined by UPLC-MS/MS. The probability evaluation model based on Monte Carlo simulation method was established after Chi-square test and One-way ANOVA of the sample contamination data. Health risk assessment was performed on the basis of margin of exposure(MOE) and margin of safety(MOS). The results showed that zearalenone(ZEN), aflatoxin B_1(AFB_1), deoxynivalenol(DON), sterigmatocystin(ST), and aflatoxin B_2(AFB_2) in the Coicis Semen samples had the detection rates of 84%, 75%, 36%, 19%, and 18%, and the mean contamination levels of 117.42, 4.78, 61.16, 6.61, and 2.13 μg·kg~(-1), respectively. According to the limit standards in the Chinese Pharmacopoeia(2020 edition), AFB_1, AFs and ZEN exceeded the standards to certain extents, with the over-standard rates of 12.0%, 9.0%, and 6.0%, respectively. The exposure risks of Coicis Semen to AFB_1, AFB2, ST, DON, and ZEN were low, while 86% of the samples were contaminated with two or more toxins, which needs more attention. It is suggested that the research on the combined toxicity of different mycotoxins should be strengthened to accelerate the cumulative exposure assessment of mixed contaminations and the formulation(revision) of toxin limit standards.

Associations of genetic variations in pyroptosis related genes with acute adverse events in postoperative rectal cancer patients receiving concurrent chemoradiotherapy / 中华肿瘤杂志

Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 (OR=0.41, 95% CI: 0.21-0.79, P=0.008), rs579408(OR=1.54, 95% CI: 1.03-2.29, P=0.034) and rs543923 (OR=0.63, 95% CI: 0.41-0.98, P=0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 (OR=0.55, 95% CI: 0.33-0.91, P=0.020) and GSDME rs2954558 (OR=1.52, 95% CI: 1.01-2.31, P=0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 (OR=0.36, 95% CI: 0.16-0.83, P=0.017), GSDME rs12540919 (OR=0.52, 95% CI: 0.27-0.99, P=0.045) and NLRP3 rs3806268 (OR=1.51, 95% CI: 1.03-2.22, P=0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P>0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P<0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.

Phytochemical interventions for post-traumatic stress disorder: A cluster co-occurrence network analysis using CiteSpace / 中西医结合学报

OBJECTIVE@#This study investigated trends in the study of phytochemical treatment of post-traumatic stress disorder (PTSD).@*METHODS@#The Web of Science database (2007-2022) was searched using the search terms "phytochemicals" and "PTSD," and relevant literature was compiled. Network clustering co-occurrence analysis and qualitative narrative review were conducted.@*RESULTS@#Three hundred and one articles were included in the analysis of published research, which has surged since 2015 with nearly half of all relevant articles coming from North America. The category is dominated by neuroscience and neurology, with two journals, Addictive Behaviors and Drug and Alcohol Dependence, publishing the greatest number of papers on these topics. Most studies focused on psychedelic intervention for PTSD. Three timelines show an "ebb and flow" phenomenon between "substance use/marijuana abuse" and "psychedelic medicine/medicinal cannabis." Other phytochemicals account for a small proportion of the research and focus on topics like neurosteroid turnover, serotonin levels, and brain-derived neurotrophic factor expression.@*CONCLUSION@#Research on phytochemicals and PTSD is unevenly distributed across countries/regions, disciplines, and journals. Since 2015, the research paradigm shifted to constitute the mainstream of psychedelic research thus far, leading to the exploration of botanical active ingredients and molecular mechanisms. Other studies focus on anti-oxidative stress and anti-inflammation. Please cite this article as: Gao B, Qu YC, Cai MY, Zhang YY, Lu HT, Li HX, Tang YX, Shen H. Phytochemical interventions for post-traumatic stress disorder: A cluster co-occurrence network analysis using CiteSpace. J Integr Med. 2023; 21(4):385-396.

Expression and Clinical Significance of Serum sFas/sFasL in Patients with Secondary Hemophagocytic Lymphohistiocytosis / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression and clinical significance of soluble Fas (sFas) and sFasL in patients with secondary hemophagocytic lymphohistiocytosis (sHLH).@*METHODS@#From September 2015 to December 2020, 86 sHLH patients who met the HLH2004 diagnostic criteria were collected. They were divided into 55 cases in the MAHLH group and 31 cases in the NonMAHLH group according to the etiology. Thirty healthy persons were chosen as the normal control group, and 20 patients with systemic lupus erythematosus (SLE) were chosen as the disease control group. The expression levels of sFas and sFasL in the serum of patients with each group were detected by ELISA, and the clinical data were collected for statistical analysis. The significance of sFas and sFasL in sHLH was analyzed by ROC curve.@*RESULTS@#Serum levels of sFas and sFasL in patients with newly diagnosed sHLH were significantly higher than those in disease control group and normal control group (P<0.01). The levels of sFas and sFasL in MAHLH group were significantly higher than those in nonMAHLH (infection related HLH and autoimmune disease related HLH) group (P<0.01). The serum levels of sFas and sFasL in 17 newly treated patients with sHLH (17/86) after treatment were significantly lower than those before treatment (P<0.01). The serum sFas level in newly diagnosed sHLH patients was positively correlated with SF(r=0.35), sCD25(r=0.79) and sFasL(r=0.73). The serum sFasL level was positively correlated with SF(r=0.39), sCD25(r=0.64) and sFas(r=0.73). Compared with the NonMAHLH group, the area under the ROC curve was 0.707 (95% CI: 0.593-0.821) (P=0.0015). The optimal critical value for diagnosing MAHLH by sFas level was 12 743 pg/ml, and the sensitivity and specificity were 70.9% and 71% respectively. Compared with the NonMAHLH group, the area under the ROC curve was 0.765(95% CI: 0.659-0.87)(P<0.01). The median OS time of sFas high expression group (≥16798.5 pg/ml) and sFasL high expression group (≥4 785 pg/ml) was significantly shorter than that of the low expression group (P<0.001).@*CONCLUSION@#Serum levels of sFas and sFasL can be used for the early diagnosis and differential diagnosis of sHLH disease, and are the factor related to the poor prognosis of sHLH.

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

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

Risk factors for neonatal asphyxia and establishment of a nomogram model for predicting neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture: a multicenter study / 中国当代儿科杂志

OBJECTIVES@#To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia.@*METHODS@#A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively.@*RESULTS@#Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia.@*CONCLUSIONS@#The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.