1.The experimental study of X-ray diagnosis of closed reduction rotational displacement of femoral neck fractures
Xinlong MA ; Jianxiong MA ; Bin LU ; Fei LI ; Haohao BAI ; Ying WANG ; Aixian TIAN ; Lei SUN ; Yan WANG ; Benchao DONG ; Hongzhen JIN ; Yan LI ; Jiahui CHEN
Chinese Journal of Orthopaedics 2024;44(2):105-113
Objective:To explore the optimal index of rotational displacement of femoral neck fractures by modeling the axial rotational displacement of femoral neck fractures after reduction and based on X-ray projections.Methods:Six dry human femur specimens, comprising 2 males and 4 females, were utilized in the study. Design and manufacture a proximal femur ortholateral and oblique X-ray casting jigs and mounts. The femoral neck fracture was modeled on the femoral specimen, with Pauwells 30°, 50°, and 70° models (2 each) made according to Pauwells typing. The fractures were manually repositioned with residual anterior 20°, 40° and 60° axial rotational displacements. Each fracture model was projected at different angles (pedicled 40°, pedicled 20°, vertical 0°, cephalad 20°, and cephalad 40°), and the trabecular angle and Garden's alignment index of the model were measured to observe the imaging characteristics of the fracture line on the medial oblique and lateral oblique radiographs.Results:In the presence of a 20° and 40° anterior rotational displacement following reduction of a femoral neck fracture, the trabecular angle in the rotationally displaced group was not significantly different from that of the anatomically repositioned group in various projection positions. However, when a residual rotational displacement of 60° was present, the trabeculae appeared blurred at most projection angles in the Pauwells 30° and 50° models, failing to measure trabecular angles. In the Pauwells 70° fracture model, the trabecular angle in the rotational displacement group was significantly different from that in the anatomical reduction group. In anteroposterior radiographs, when the anterior rotation displacement was 60° in the Pauwells 70° group, Garden's contralateral index showed an unsatisfactory restoration (150°, 142°), whereas all rotationally displaced models in the Pauwells 30° and Pauwells 50° groups had a Garden's contralateral index of >155°, which achieved an acceptable restoration. In lateral radiographs, all rotational displacement models with Garden's alignment index>180° failed to achieve acceptable repositioning, and the larger the Pauwells angle the greater the Garden's alignment index at the same rotational displacement. In the internal oblique position with a bias towards the foot side, the image showed partial overlap between the femoral head and the shaft, making it difficult to assess the quality of the reduction. Conversely, when projected cephalad, the femoral neck appeared longer, particularly at a projection angle of 40° cephalad, allowing for clear observation of the fracture line and the anatomy of the proximal femur. The trabeculae were not well visualized in the external oblique position.Conclusion:There are limitations in applying the trabecular angle to assess the axial rotational displacement of the femoral head after reduction of femoral neck fractures. The Pauwells 70° with residual rotational anterior displacement of 60° was the only way to detect axial rotational displacement of the femoral head on anteroposterior radiographs Garden's alignment index. For the determination of axial rotational displacement of the femoral head, the Garden's alignment index on lateral radiographs provides higher reliability.
2.Production of SARS-CoV-2 Omicron Variant Main Protease for Screening Approved Drugs as Its Potential Inhibitors
Haohao YAN ; Rui ZHANG ; Zhicheng LIU ; Xiaoli LIU ; Xiaoping LIU ; Yunyu CHEN
Chinese Journal of Modern Applied Pharmacy 2024;41(2):213-220
OBJECTIVE
To develop a high-throughput screening assay for the discovery of Omicron variant main protease(OM-Mpro) inhibitors based on the principle of fluorescence resonance energy transfer(FRET).
METHODS
The recombinant OM-Mpro enzyme was expressed in Escherichia coli Rosetta(DE3) cells, and further purified by a HisTrapTM chelating column. Subsequently, the enzymatic activity of OM-Mpro and wild type main protease(WT-Mpro) enzymes and inhibition of nirmatrelvir against both proteases were measured using FERT assay. With the FRET assay, OM-Mpro inhibitors were identified via high-throughput screening of an approved drug library.
RESULTS
The active OM-Mpro enzyme was successfully prepared from E. coli cells. OM-Mpro and WT-Mpro enzymes possessed the same enzymatic activity, and OM-Mpro remained susceptible to nirmatrelvir in vitro. Through high-throughput screening of the marketed drug library, it was found that cetylpyridinium chloride(CPC) is a mixed-type OM-Mpro inhibitor in vitro with an IC50 value of 8.76 μmol·L−1.
CONCLUSION
A robust FRET assay has been successfully developed based on the production of active OM-Mpro enzyme for screening of its inhibitors, and CPC is identified as a potential lead compound against OM-Mpro in vitro. This study provides a promising avenue for rapid discovery of broad-spectrum antivirals against coronavirus protease.
3.Research progress on immune checkpoint inhibitors for the treatment of mismatch re-pair-deficient/microsatellite instability-high gastric cancer
Liu QINGHUA ; Wang HAOHAO ; Chen QINGJIE ; Luo RUIYING ; Luo CHANGJIANG
Chinese Journal of Clinical Oncology 2024;51(11):580-584
Mismatch repair-deficient/microsatellite instability-high(dMMR/MSI-H)gastric cancer represents a distinct molecular subtype of tumors characterized by pronounced sensitivity to immune checkpoint inhibitors(ICIs)attributed to its unique immune microenvironment and elevated mutation burden.Various clinical studies underscore the efficacy of ICIs in treating dMMR/MSI-H gastric cancer;however,chal-lenges such as primary and acquired resistance persist.Overcoming resistance and identifying optimal ICIs for its treatment remain critical clinical issues.This review delineates the mechanisms of ICIs,recent advances in their therapeutic application for dMMR/MSI-H gastric can-cer,and ongoing challenges in combating resistance,aiming to guide clinical practice effectively.
4.Feasibility analysis of femoral anteversion angle measurement based on three-dimensional femoral model
Jiahui CHEN ; Xinlong MA ; Jianxiong MA ; Ying WANG ; Haohao BAI ; Bin LU ; Shixiong ZHANG
Chinese Journal of Orthopaedics 2024;44(19):1288-1295
Objective:To propose a method to measure the femoral anteversion angle based on the three-dimensional model of femur.Methods:From January 2019 to December 2023, a total of 50 patients (100 femurs) with patellar instability who underwent full-length CT examination of both lower limbs in Tianjin Hospital were retrospectively analyzed, including 16 males and 34 females, aged 28.5±11.9 years (range, 16-57 years). All patients underwent CT examination of both lower limbs, and the imaging data were imported into Mimics 21.0 software as DICOM format files. The femur was extracted by the threshold segmentation function, and the 3D model of the femur was reconstructed by appropriate trimming and smoothing. Three-dimensional models of the femur from 30 patients (60 femurs) were selected and imported into 3-matic 13.0 software for labeling of anatomical points and drawing of axes. The angle between the axis of the distal femur and the axis of the proximal femur was the femoral anteversion angle. Two observers positioned the spatial coordinates of the intercondylar fossa apex, the greater trochanter apex, the center of the femoral head, the femoral through-condylar axis and the posterior condylar tangent marker points on a 3D model of the femur to compare the differences between the groups. The femoral anteversion angles measured by different three-dimensional measurement methods were compared with the clinically reported femoral anteversion angles.Results:The difference between the femoral head center and intercondylar fossa apex coordinate data of 30 patients (60 femurs) measured by the two observers was not statistically significant ( P>0.05), whereas the data for the Y-axis coordinate of the greater trochanter apex were 25.77±23.21 and 22.08±25.73, respectively, and the difference was statistically significant ( t=2.906, P=0.017). The difference between the data of femoral through condylar and posterior condylar tangential coordinates of 30 patients (60 femurs) measured by the two observers was not statistically significant ( P>0.05). Using the femoral mechanical axis as the projection direction, the angle between the transcondylar axis and the posterior condylar tangent line was 5.97°±2.02° (range, 1.48°-12.08°). The anterior tilt of the femur measured by the two observers in the femoral neck cylinder fitting method was 23.35°±7.45° and 24.94°±9.01°, respectively, and the difference was statistically significant ( t=-2.147, P=0.040). The anterior inclination of the femur measured by the two observers in the femoral head ball enlargement method was 24.63°±7.66° and 25.12°±8.84°, the difference was not statistically significant ( t=-0.820, P=0.419). Using the femoral head ball expansion method to locate the proximal femoral axis, two observers measured the anterior tilt angle of the femur in 50 patients (100 femurs) according to the method described above, which was 23.30°±9.41° and 23.57°±9.97°, respectively, without a statistically significant difference ( t=-0.664, P=0.508), both smaller than the 29.56°±8.74° measured based on two-dimensional images in the imaging report, and the difference was statistically significant ( P<0.05). Conclusion:The femoral anteversion angle measured by the angle between the axis of the femoral condyle and the axis of the femoral neck based on the three-dimensional model is accurate and effective, and the measured value is smaller than that based on the two-dimensional images in clinical practice.
5.Changes in the subfoveal choroidal thickness of children and adolescents with different refractive states
Jinling ZHANG ; Yujie LIAO ; Xiaoyan YU ; Qi YANG ; Jiaqing KANG ; Jiawen LU ; Chen CHEN ; Haohao ZHU
Recent Advances in Ophthalmology 2024;44(11):883-886
Objective To observe the changes in the subfoveal choroidal thickness(SFCT)of children and adoles-cents with different refractive states using optical coherence tomography angiography.Methods A total of 171 children and adolescents were followed.They were divided into the lower primary school group(6-8 years old),upper primary school group(9-11 years old),and junior high school group(12-14 years old)according to their age at the time of en-rollment.Dioptric examinations(including best corrected visual acuity,diopter,intraocular pressure,corneal curvature,axial length and SFCT)were performed,data collection was conducted twice in half a year(initial examination and review after half a year),and the eyeball parameters and changes in eyeball parameters after half a year among all groups were compared.Results The axial length and SFCT of subjects had significant differences among all groups(both P<0.05).In children and adolescents,the axial length gradually lengthened and SFCT gradually thickened with age,while intraocular pressure and corneal curvature were not associated with age(both P>0.05).In the initial examination and review after half a year,there was no significant difference in intraocular pressure,corneal curvature and SFCT of subjects with differ-ent refractive states in all groups(all P>0.05),while the axial length of myopic subjects was greater than that of non-my-opic subjects in all groups(all P<0.05).In the review after half a year,the SFCT of non-myopic subjects in the lower pri-mary school group and upper primary school group was significantly thickened(P<0.001,P=0.003),while there was no significant difference in SFCT of myopic subjects in all groups compared with the value half a year ago(all P>0.05).The axial length of all subjects showed a positive correlation with the SFCT in the initial examination and review after half a year(r=0.354,0.228,P<0.05).Conclusion Myopia affects the increase in SFCT in children and adolescents.
6.Evaluation of MTBDRplus 2.0 in the diagnosis of drug resistance of Mycobacterium tuberculosis
RU Haohao ; YANG Xing ; CHEN Lianyong ; CHEN Tao ; YAN Shuangqun ; XU Lin
China Tropical Medicine 2024;24(3):271-
Objective To evaluate the sensitivity and specificity of the GenoType MTBDRplus V2.0 (Mycobacterium tuberculosis and resistance gene detection assay kit using PCR-linear probe hybridization with enzyme chromogenic method, referred to as MTBDRplus 2.0) kit for detection of rifampin and isoniazid resistance, providing the basis for improving the detection of drug-resistant Mycobacterium tuberculosis. Methods From January to December 2022, positive strains of Mycobacterium tuberculosis isolated and cultured from designated tuberculosis treatment hospitals in 32 counties (cities, districts) of Yunnan Province were collected. Resistance in 880 strains of Mycobacterium tuberculosis was detected by MTBDRplus 2.0, and the minimum inhibitory concentration (MIC) method was used for the drug sensitivity test. Results Using the MIC method as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value of MTBDRplus 2.0 in detecting isoniazid resistance were 67.69%, 98.40%, 77.19%, and 97.45%, respectively. The consistency of the linear probe method and MIC method in detecting isoniazid resistance was moderate, with a Kappa value of 0.701 (P<0.001); the sensitivity, specificity, positive predictive value, and negative predictive values of MTBDRplus 2.0 in detecting rifampicin resistance were 87.80%, 99.40%, 87.80%, and 99.40%, respectively. The consistency of rifampicin resistance detection between MTBDRplus 2.0 and MIC method was relatively good, with a Kappa value of 0.872 (P<0.001). Among the 13 strains showing resistance to isoniazid with MTBDRplus 2.0, but sensitivity according to the MIC method, 11 strains (84.62%) had mutations in the inhA gene (C15T). Out of the 5 strains showing resistance to rifampicin with MTBDRplus 2.0, but sensitivity according to the MIC method, 4 strains (80.00%) had other mutations in the rpoB gene. Conclusions MTBDRplus 2.0 shows high sensitivity and specificity in detecting rifampicin resistance, but slightly low sensitivity in detecting isoniazid resistance. The low sensitivity in detecting isoniazid resistance may be due to insufficient target coverage of the detection kit. inhA gene mutations are poorly correlated with isoniazid resistance, and other mutations in the rpoB gene are poorly correlated with rifampicin resistance.
7.Analyzing the influencing factors of sleep quality of coal miners in a company in Shanxi Province
Li LI ; Yingjun CHEN ; Liuquan JIANG ; Lürong LI ; Xiaolan ZHEN ; Zhizhong YANG ; Haohao GUO ; Gaisheng LIU
China Occupational Medicine 2023;50(6):651-656
{L-End}Objective To investigate the current status of sleep quality and its influencing factors among coal miners in a company in Shanxi Province. {L-End}Methods A total of 1 047 coal miners from a coal mine company in Shanxi Province were selected as the study subjects by convenient sampling method. The occupational stress, occupational burnout and sleep quality of the study subjects were investigated using Occupational Stress Core Scale, Maslach Burnout Inventory-General Survey and Pittsburg Sleep Quality Index Scale. {L-End}Results The detection rates of occupational stress, occupational burnout, sleep disorder were 58.9%, 59.1% and 57.9%, respectively. The result of multivariate logistic regression analysis showed that education level, alcohol consumption, work shift, duration of dust-exposure, phase of respiratory symptoms, self-assessment of health, occupational stress and occupational burnout were independent influencing factors of sleep disorders in the coal miners (all P<0.05). Among them, the risk of sleep disorders in drinkers was higher than that in non-drinkers (P<0.05); the risk of sleep disorders was higher in miners working in a rotating work shift with two shifts than in those with three shifts (P<0.05); the higher the education level, the longer the duration of dust-exposure, the more serious the phase of respiratory symptoms, the worse the self-assessment of health, the higher the degree of occupational stress and the higher the degree of occupational burnout, the higher the risk of sleep disorders (all P<0.05). {L-End}Conclusion The incidence of sleep disorders in coal miners in this company is relatively high. Occupational stress, occupational burnout, education level, alcohol consumption, work shift, duration of dust-exposure, respiratory symptoms and health status are risk factors for sleep disorders in coal miners.
8. Investigation of treatment and analysis of prognostic risk on enterocutaneous fistula in China: a multicenter prospective study
Tao ZHENG ; Haohao XIE ; Xiuwen WU ; Qiang CHI ; Feng WANG ; Zhenhua YANG ; Chaowu CHEN ; Wei MAI ; Suming LUO ; Xiaofei SONG ; Shimin YANG ; Wei ZHOU ; Haiyan LIU ; Xinjian XU ; Zheng ZHOU ; Chuanyuan LIU ; Lian′an DING ; Kai XIE ; Gang HAN ; Hongbin LIU ; Jianzhong WANG ; Shichen WANG ; Peige WANG ; Gefei WANG ; Guosheng GU ; Jian′an REN
Chinese Journal of Gastrointestinal Surgery 2019;22(11):1041-1050
Objective:
To investigate the diagnosis and treatment for enterocutaneous fistula (ECF) in China, and to explore the prognostic factors of ECF.
Methods:
A multi-center cross-sectional study was conducted based on the Registration System of Chinese Gastrointestinal Fistula and Intra-Abdominal Infections to collect the clinical data of ECF patients from 54 medical centers in 22 provinces/municipalities from January 1, 2018 to December 31, 2018. The clinical data included patient gender, age, length of hospital stay, intensive care unit (ICU) admission, underlying diseases, primary diseases, direct causes of ECF, location and type of ECF, complications, treatment and outcomes. All medical records were carefully filled in by the attending physicians, and then re-examined by more than two specialists. The diagnosis of ECF was based on the clinical manifestations, laboratory/imaging findings and intraoperative exploration.
Results:
A total of 1521 patients with ECF were enrolled, including 1099 males and 422 females, with a median age of 55 years. The top three primary diseases of ECF were malignant tumors in 626 cases (41.2%, including 540 gastrointestinal tumors, accounting for 86.3% of malignant tumors), gastrointestinal ulcers and perforations in 202 cases (13.3%), and trauma in 157 cases (10.3%). The direct causes of ECF were mainly surgical operation in 1194 cases (78.5%), followed by trauma in 156 (10.3%), spontaneous fistula due to Crohn
9.Therapeutic efficacy and safety of domestic bortezomibˉbased chemotherapy in treatment of multiple myeloma
Haohao HAN ; Lijie HAN ; Feifei WU ; Silin GAN ; Jie MA ; Shengmei CHEN ; Chong WANG ; Yanfang LIU ; Haizhou XING ; Zhongxing JIANG ; Xinsheng XIE ; Yingmei LI ; Weijie CAO ; Ling SUN ; Hui SUN
Journal of Leukemia & Lymphoma 2019;28(5):268-272
Objective To investigate the efficacy and safety of domestic bortezomibˉbased chemotherapy for patients with multiple myeloma (MM). Methods The clinical data of 60 MM patients treated with domestic bortezomibˉbased chemotherapy regimen (the observation group) in the First Affiliated Hospital of Zhengzhou University from April 2018 to October 2018 were retrospectively analyzed, which were compared with 112 MM patients treated with original treatment regimen (the control group) at the same hospital from November 2010 to November 2014. According to the disease stage, the patients were divided into newly diagnosed MM (NDMM) group and relapsed refractory MM (RRMM) group, and efficacy and adverse reactions of domestic bortezomib were evaluated. Results The total response rate (ORR) of the observation group was 71.7% (43/60), severe complete response (sCR) + complete response (CR) rate was 16.7% (10/60), very good partial response (VGPR) rate was 18.3% (11/60), and partial response (PR) rate was 36.7% (22/60). The ORR of NDMM group (45 cases) and RRMM group (15 cases) was 82.2% (37/45) and 40.0% (6/15), respectively, and the difference was statistically significant (χ2= 9.877, P < 0.05). There was no significant difference between ISS stage Ⅰ+Ⅱ and stage Ⅲ [ORR: 75.7% (28/37) vs. 65.2% (15/23), respectively; χ2=0.764, P >0.05]. ORR and CR rates in the NDMM group and RRMM group of the observation group and the control group were not statistically different (all P>0.05). In the treatment of bortezomibˉbased chemotherapy, the common adverse reaction was peripheral neuropathy, mostly belonging to grade 1-2. Other side effects included hematocytopenia, gastrointestinal events and herpes zoster, which could be alleviated or restored to normality after supportive treatments. One patient died of pulmonary infection, respiratory failure and septic shock during the intermittent period of chemotherapy. Conclusion ORR of domestic bortezomibˉbased chemotherapy in treatment of the patients with MM is high, and the incidence of adverse reactions shows no significant increase compared with original drugs.
10. A study on genotype of 271 mycobacterium tuberculosis isolates in 6 prefectures in Yunnan Province
Lianyong CHEN ; Xing YANG ; Haohao RU ; Huijuan YANG ; Shuangqun YAN ; Li MA ; Jin'ou CHEN ; Rui YANG ; Lin XU
Chinese Journal of Preventive Medicine 2018;52(1):62-67
Objective:
To understand the characteristics of genotypes of Mycobacterium tuberculosis isolates in Yunnan province, and provide the molecular epidemiological evidence for prevention and control of tuberculosis in Yunnan Province.
Methods:
Mycobacterium Tuberculosis isolates were collected from 6 prefectures of Yunnan province in 2014 and their Genetypes of Mycobacterium tuberculosis isolates were obtained using spoligotyping and multiple locus variable numbers of tandem repeats analysis (MLVA). The results of spoligotyping were entered into the SITVITWEB database to obtain the Spoligotyping International Type (SIT) patterns and the sublineages of MTB isolates. The genoyping patterns were clustered with BioNumerics (version 5.0).
Results:
A total of 271 MTB isolates represented patients were collected from six prefectures in Yunnan province. Out of these patients, 196 (72.3%) were male. The mean age of the patients was (41.9±15.1) years. The most MTB isolates were from Puer, totally 94 iusolates(34.69%). Spoligotyping analysis revealed that 151 (55.72%) MTB isolates belonged to the Beijing genotype, while the other 120 (44.28%) were from non-Beijing genotype; 40 genotypes were consisted of 24 unique genotypes and 16 clusters. The 271 isolates were differentiated into 30 clusters (2 to 17 isolates per cluster) and 177 unique genotypes, showing a clustering rate of 23.62%. Beijing genotype strains showed higher clustering rate than non-Beijing genotype strains (29.14% vs 16.67%). The HGI of 12-locus VNTR in total MTB strains, Beijing genotype strains and non-Beijing genotype was 0.993, 0.982 and 0.995 respectively.
Conclusion
The Beijing genotype was the predominant genotype in Yunnan Province, the characteristics of Mycobacterium tuberculosis showed high genetic diversity. The genotyping data reflect the potential recent ongoing transmission in some area, which highlights the urgent need for early diagnosis and treatment of the infectious TB cases, to cut off the transmission and avoid a large TB outbreak.


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