Objectives:To develop and validate predictive models for esophageal squamous cell carcinoma (ESCC) using circulating cell-free DNA (cfDNA) terminal motif analysis. The goal was to improve the non-invasive detection of early-stage ESCC and its precancerous lesions.Methods:Between August 2021 and November 2022, we prospectively collected plasma samples from 448 individuals at the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences for cfDNA extraction, library construction, and sequencing. We analyzed 201 cases of ESCC, 46 high-grade intraepithelial neoplasia (HGIN), 46 low-grade intraepithelial neoplasia (LGIN), 176 benign esophageal lesions, and 29 healthy controls. Participants, including ESCC patients and control subjects, were randomly assigned to a training set ( n=284) and a validation set ( n=122). The training cohort underwent z-score normalization of cfDNA terminal motif matrices and a selection of distinctive features differentiated ESCC cases from controls. The random forest classifier, Motif-1 (M1), was then developed through principal component analysis, ten-fold cross-validation, and recursive feature elimination. M1's efficacy was then validated in the validation and precancerous lesion sets. Subsequently, individuals with precancerous lesions were included in the dataset and participants were randomly allocated to newly formed training ( n=243), validation ( n=105), and test ( n=150) cohorts. Using the same procedure as M1, we trained the Motif-2 (M2) random forest model with the training cohort. The M2 model's accuracy was then confirmed in the validation cohort to establish the optimal threshold and further tested by performing validation in the test cohort. Results:We developed two cfDNA terminal motif-based predictive models for ESCC and associated precancerous conditions. The first model, M1, achieved a sensitivity of 90.0%, a specificity of 77.4%, and an area under the curve (AUC) of 0.884 in the validation cohort. For LGIN, HGIN, and T1aN0 stage ESCC, M1's sensitivities were 76.1%, 80.4%, and 91.2% respectively. Notably, the sensitivity for jointly predicting HGIN and T1aN0 ESCC reached 85.0%. Both the predictive accuracy and sensitivity increased in line with the cancer's progression ( P＜0.001). The second model, M2, exhibited a sensitivity of 87.5%, a specificity of 77.4%, and an AUC of 0.857 in the test cohort. M2's sensitivities for detecting precancerous lesions and ESCC were 80.0% and 89.7%, respectively, and it showed a combined sensitivity of 89.4% for HGIN and T1aN0 stage ESCC. Conclusions:Two predictive models based on cfDNA terminal motif analysis for ESCC and its precancerous lesions are developed. They both show high sensitivity and specificity in identifying ESCC and its precancerous stages, indicating its potential for early ESCC detection.

Objectives:To develop and validate predictive models for esophageal squamous cell carcinoma (ESCC) using circulating cell-free DNA (cfDNA) terminal motif analysis. The goal was to improve the non-invasive detection of early-stage ESCC and its precancerous lesions.Methods:Between August 2021 and November 2022, we prospectively collected plasma samples from 448 individuals at the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences for cfDNA extraction, library construction, and sequencing. We analyzed 201 cases of ESCC, 46 high-grade intraepithelial neoplasia (HGIN), 46 low-grade intraepithelial neoplasia (LGIN), 176 benign esophageal lesions, and 29 healthy controls. Participants, including ESCC patients and control subjects, were randomly assigned to a training set ( n=284) and a validation set ( n=122). The training cohort underwent z-score normalization of cfDNA terminal motif matrices and a selection of distinctive features differentiated ESCC cases from controls. The random forest classifier, Motif-1 (M1), was then developed through principal component analysis, ten-fold cross-validation, and recursive feature elimination. M1's efficacy was then validated in the validation and precancerous lesion sets. Subsequently, individuals with precancerous lesions were included in the dataset and participants were randomly allocated to newly formed training ( n=243), validation ( n=105), and test ( n=150) cohorts. Using the same procedure as M1, we trained the Motif-2 (M2) random forest model with the training cohort. The M2 model's accuracy was then confirmed in the validation cohort to establish the optimal threshold and further tested by performing validation in the test cohort. Results:We developed two cfDNA terminal motif-based predictive models for ESCC and associated precancerous conditions. The first model, M1, achieved a sensitivity of 90.0%, a specificity of 77.4%, and an area under the curve (AUC) of 0.884 in the validation cohort. For LGIN, HGIN, and T1aN0 stage ESCC, M1's sensitivities were 76.1%, 80.4%, and 91.2% respectively. Notably, the sensitivity for jointly predicting HGIN and T1aN0 ESCC reached 85.0%. Both the predictive accuracy and sensitivity increased in line with the cancer's progression ( P＜0.001). The second model, M2, exhibited a sensitivity of 87.5%, a specificity of 77.4%, and an AUC of 0.857 in the test cohort. M2's sensitivities for detecting precancerous lesions and ESCC were 80.0% and 89.7%, respectively, and it showed a combined sensitivity of 89.4% for HGIN and T1aN0 stage ESCC. Conclusions:Two predictive models based on cfDNA terminal motif analysis for ESCC and its precancerous lesions are developed. They both show high sensitivity and specificity in identifying ESCC and its precancerous stages, indicating its potential for early ESCC detection.

Objectives: To evaluate the association of illicit drug use with bone mineral density (BMD) and hip geometric parameters at the narrow neck. Methods: This is a cross-sectional matched cohort study conducted in the Hong Kong Chinese population. Associations with illicit drug use were estimated using linear regression for BMD (lumbar spine and femoral neck) and hip geometrical parameters (cross-sectional area [CSA], cross-sectional moment of inertia [CSMI], section modulus [SM], average cortical thickness [ACT] and BMD at the narrow neck) after adjusting for age, body mass index (BMI), smoking status, drinking status, physical activity, and history of antipsychotic and antidepressant use. Mean difference and 95% confidence intervals (95% CI) were calculated between 108 illicit drug users and 108 controls using an adjusted linear model and cluster-robust standard errors after matching by age and sex. The false discovery rate was used to correct for multiple testing. Results: Illicit drug users had a significantly lower BMD (g/cm2 ) at the lumbar spine (mean difference: -0.062; 95% CI: -0.108 to − 0.015), and femoral neck (mean difference: -0.058; 95% CI: -0.106 to − 0.010) in the fully adjusted model. Illicit drug users also had a significantly lower CSA (mean difference: -0.238 cm2 ; 95% CI: -0.462 to − 0.013), ACT (mean difference: -0.018 cm; 95% CI: -0.030 to − 0.006) and BMD (mean difference: -0.070 g/ cm2 ; 95% CI: -0.128 to − 0.012) at the narrow neck. Conclusions Illicit drug use is associated with lower BMD and bone strength. Future studies evaluating the risk of illicit drug use with fragility fracture are warranted.

Objective To understand the prevalence and risk factors of Blastocystis hominis infection in inpatients in Jiangjin District, Chongqing City. Methods A cross-sectional study was conducted in a community hospital in Jiangjin District, Chongqing City, and the inpatients were surveyed by questionnaires. After obtaining the informed consent from the inpatients or legal guardians, the stool and blood samples were collected and examined by microscopy and PCR from April 17 to May 1, 2018. The univariate analysis and logistic regression analysis were used to analyze the risk factors of the B. hominis infection. Results A total of 198 hospitalized patients were investigated, and the infection rate of B. hominis was 10.61% (21/198), and the infection rate of the females (12.10%) was higher than that of the males (8.11%), but the difference was not statistically significant. The highest rate of infection was 19.23% in the age group of 10 to 20 years, followed by 17.74% in the age group of 60 years and above, and the lowest rate was 2.38% in the age group of 20 to 40 years. The difference in infection rates of B. hominis among the different age groups was statistically significant (P < 0.05). The infection rate of B. hominis in the people who used dry pail latrines was 33.30%, which was higher than that of the people who used water flush toilets (9.10%) (P < 0.05). The genotypes of B. hominis were ST1, ST3, ST6 and ST7, and ST6 and ST3 being the most predominant genotypes which accounted for 47.62% (10/21) and 38.10% (8/21) respectively, and among the infected males, the genotypes were only ST3 and ST6. The multiple logistic regression analysis showed that among the factors affecting B. hominis infection, only keeping pets was a risk factor [OR = 3.798, 95% CI (1.245, 11.581), P < 0.05]. Conclusion A high prevalence of B. hominis infection is found in the inpatients in Jiangjin District, Chongqing City, the predominant genotypes are ST6 and ST3, and keeping pets may be one of the main risk factors.

Objective To investigate the prevalence and risk factors of Blastocystis hominis infections among patients with HIV/AIDS in Fuyang City, Anhui Province. Methods A cross-sectional study was conducted in Fuyang City, Anhui Province in 2016. The demographic and socioeconomic status, and the lifestyle and production style were collected using a questionnaire survey. B. hominis DNA was detected in subjects’stool samples using a PCR assay, and the CD4+ T lymphocyte count and HIV viral load were measured in the subjects’ blood samples. The risk factors of B. hominis infections among patients with HIV/AIDS were identified using univariate and multivariate logistic regression analyses. Results A total of 398 HIV/AIDS patients were enrolled in this study, with a mean age of 49.3 years, a mean body weight of 55.9 kg and a mean height of 164.4 cm. The prevalence of B. hominis infection was 6.78% in the study subjects, and no gender- (χ² = 1.589, P = 0.207), education level- (χ² =0.508, P = 0.776), marital status- (χ² = 0.419, P = 0.811) or occupation-specific prevalence (χ² = 2.744, P = 0.615) was detected. Among the patients with HIV/AIDS, there were no significant differences in the age (t = 0.370, P = 0.712), height (t = 1.587, P =0.113), body weight (t = 0.516, P = 0.606), CD4⁺ T lymphocyte count (t = 1.187, P = 0.230) or HIV viral load (t = 0.193, P =0.496) between B. hominis-infected and uninfected individuals. Dinking non-tap water [OR = 6.554, 95% CI: (1.876 to 22.903)] and keeping dogs [OR = 5.895, 95% CI: (2.017 to 17.225)] were identified as risk factors for B. hominis infection in patients with HIV/AIDS. Conclusion The prevalence of B. hominis infection is high in HIV/AIDS patients, and drinking non-tap water and keeping dogs are risk factors for B. hominis infection among HIV/AIDS patients.

OBJECTIVETo investigate the hemostatic effect of spleen-invigorating, qi-replenishing and blood-containing formula on simvastatin-induced zebrafish hemorrhage model, and to compare with the effect of clearing heat and cooling blood formula.

METHODSZebrafishes from breed A B line were treated with 0.5 µmol/L simvastatin for 24 hours to establish zebrafishes hemorrhage model. Under strict blinded experimental conditions, the above mentioned zebrafishes were then treated with experimental drug of different concentrations at the maximum non-lethal dose. The intervention effect of spleen-invigorating, qi-replenishing and blood-containing formula was comprehensively assessed by examining the main observational parameters, such as bleeding reduction rate and hemostasis rate while referring to additional parameters, such as blood flow, improvement rate of blood flow, velocity of movement, improvement rate of motion, which are characteristics of spleen qi deficiency.

RESULTSWhen the hemostatic effect of experimental drug B1 at the concentrations of 500 and 1 000 µg/ml, zebrafish bleeding rates were 30% and 15%, the hemostatic rate was 60% and 80%, respectively; when the experimental drug B2 at concentration of 500 and 1 000 µg/ml, Zebrafish bleeding rates were 45% and 40%, the hemostatic rate was 40% and 47%, respectively, showing that experimental drug B1 was superior to B2 in terms of decreasing bleeding rate and improving hemostatic effect in zebrafish. In the equal concentration, the experimental drug B1 was superior to B2 in terms of increasing and improving the blood flow of hemorrhagic zebrafish. Promotion and improvement of motion: in equal concentration, experimental drug B1 was superior to B2 in terms of promoting the motion velocity and increasing the improving rate of motion in zebrafish.

CONCLUSIONThe spleen-invigorating, qi-replenishing and blood-containing formula displays a good hemostatic effect on simvastatin-induced hemorrhage of zebrafish. It also boosts the blood flow and motion velocity in hemorrhagic zebrafish, therefore, providing an experimental basis for the treatment of syndrome of spleen failing to control blood by spleen-invigorating, qi-replenishing and blood-containing formula.

Objective To investigate pathogenic bacteria distribution and drug resistance of the bacteria isolated from Chinese young and mid-age patients (14-65 years).Methods Collect and monitor the isolates from young and mid-aged patients (14-65 years) in 557 mem-ber hospitals of Grade three between January 1 and December 31 in 2012.Disk diffusion and automatic machine method are applied to anti-biotic resistance test.The data were analyzed and processed with software WHONET 5.6.Results There are 383443 isolates from young and mid-aged patients in 557 hospitals of Grade three.Gram-negative bac-teria is account for 69.33%, the major strains are Escherichia coli of 78915, Klebsiella pneumoniae of 48698, Pseudomonas aeruginosa of 36239 and Acinetobacter baumannii of 27858, respectively;Gram-posi-tive bacteria is account for 30.67%, Staphylococcus aureus of 33328, Staphylococcus epidermidis of 18818, Enterococcus faecalis of 13114 and Enterococcus faecium of 8517 are the top four.It was not found that Staphylococcus spp.were resistant to vancomycin and linezolid, and there were teicoplanin resistant oagulase -negative Staphylococcus account for 3.4%, Vancomycin resistant Enterococcus faecium 3.2%, Vancomycin resistant Enterococcus faecalis 1.5%.Frequen-cy of extended spectrum beta lactamase ( ESBLs) in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis are separately 58.4%, 33.6%and 24.9%, which increase resistance to imipenem as 2.8%, 6.5%and 4.1%contrast to last year.Rate of carbapenem resistant to Acinetobacter baumannii was about 50%, only polymixin B has better ac-tivity 96.7%.Haemophilus were isolated less among the young and mid-aged patients, but were sensitive to most an-tibiotic.Conclusion Antibiotic resistant rate of young and mid-aged patients in China are more serious, especially increase of ESBLs producing Enterobacteriaceae, multi drug resistant non-fermenting bacteria and vancomycin resistant Enterococcus.Meanwhile, the resistant trend is various by time, so that it is important and tedious work to monitor the antibiotic resistance.

Aged ; Fatty Liver ; complications ; metabolism ; Female ; Humans ; Insulin Resistance ; Lipids ; Liver ; metabolism ; Male ; Metabolic Diseases ; metabolism ; Middle Aged ; Non-alcoholic Fatty Liver Disease

Objective To study the bone biomechanics of the rabbit osteoporosis models induced by dexamethasone sodium phosphate injection (DX) using a combined treatment modality of 99Tc-MDP and GuKangLing.Methods Rabbits were intramuscularly injected with DX (2 mg/kg) twice a week for 6 weeks.The animal osteoporosis model group (Group C) and normal group (Group A) were compared to confirm the model was available.Another control group (Group B),the osteoporosis control group (Group D) were set for the comparison at the end of the experiment.The 99Tc-MDP therapy group (Group E),GuKangLing therapy group (Group F) and 99Tc-MDP plus GuKangLing therapy group (Group G) were included in the study.The treatment lasted for 16 weeks.The bone biomechanics,cytopathology bone histomorphology,bone mineral density (BMD),X-ray,CT,bone scintigraphy and serum bone alkaline phosphatase (BALP)and P (bone gla protein) were chosen as the markers or methods to evaluate the treatment results (excellent,effective and invalid).The analysis of variance (ANOVA) and t-test were used for group comparison analysis.Results Cytopathology result indicated that there was no bone trabecula destruction in Group A.However,there was distinct bone destruction in Group C.The bone biomechanics (left femur head (265.914 ±52.773) N,L4(369.671 ±94.919) N),BMD(left femur (0.238 ±0.016) g/cm2,L4(0.236 ±0.016) g/cm2)and bone histomorphology ( (66.230 ± 10.848) ％ ) in Group C reduced clearly as compared with Group A ((405.343±55.410) N,(750.870±53.718) N,(0.294±0.017) g/cm2,(0.302±0.023) g/cm2,( 131.500 ± 21.846) ％ ) ( t ≥4.550,all P ＜ 0.01 ).Radionuclide bone scan also showed that the uptake of tracers was higher by the main arthrosis in Group C than that in Group A.Vertebra was not clearly visualized on bone scan image.There were significant differences between Group A and Group C in serum BALP and P ((45.000±7.303) vs (12.485 ±1.512) U/L,(0.168±0.018) vs (0.115 ±0.017) μg/L,t =4.126,5.476,both P ＜ 0.01 ),which indicated that the animal osteoporosis model was available.The pathological results showed an improved recovery of bone structure and trabecular in Groups E and G,but a worse recovery in Group F.Biomechanics result in Groups E and G (left femur head (386.457 ±77.077) N and (432.771 ± 17.525) N,L4(649.550 ± 126.859) N and (655.443 ±76.555) N) improved apparently,which were similar to Group B.The radiotracer uptake in Group F was lower than that in group D.The bone biomechanics,bone histomorphology,BMD,serum BALP and P after the treatment showed significant differences in Groups E,F and G (F:8.556 - 31.608,all P＜0.01 ),and the bone biomechanics result in Group G was a little better than that in Group E (t =2.625,P ＜ 0.05 ).The results of Group G and E were considered as excellent,and Group F was considered as effective.Conclusions The treatment of 99Tc-MDP combined with GuKangLing could improve the bone biomechanics of rabbit osteoporosis models and may be a potential method to increase the bone strength for resisting external force.

OBJECTIVETo probe the implant-bone-interface stress distribution of zygomatic implant denture concerning different implant sites.

METHODSThree-dimensional finite element model for severe atrophy maxillary posterior-tooth area was established biomechanically in this study by computer technique and zygomatic implant was simulated into the model in the first-maxillary-premolar region, the second-maxillary-premolar region, the first-maxillary-molar region and the second-maxillary-molar region respectively. Vertical loading, buccal (30 degrees) loading and lingual (30 degrees) loading were preformed, 100 N. Then these load cases were calculated and analyzed.

RESULTS1) When the implant site was placed in the first-maxillary-premolar region, the buccal side of zygomatic implant exposed out of the bone and didn't meet the clinical request. 2) As far as the tensile stress peak value in the maxillary posterior-tooth area was concerned, the highest value was recorded when the implant was placed in the second-maxillary-molar region, and then the medium value was recorded when the implant was placed in the second-maxillary-premolar region, and the smallest was recorded when the implant in the first-maxillary-molar region. As far as the compressive stress peak value in the maxillary posterior-tooth area was concerned, the highest value was recorded when the implant was placed in the second-maxillary-molar region, and then the medium was recorded when the implant was in the first-maxillary-molar region, and the smallest value was presented when the implant was in the second-maxillary-premolar region. As far as the tensile and compressive stress peak values in the zygomatic area were concerned, the highest value was recorded when the implant was in the second-maxillary-premolar region, and then the medium value when the implant was in the first-maxillary-molar region, and the smallest when the implant was in the second-maxillary-molar region.

CONCLUSIONThe first-maxillary-molar region is the best implant site of zygomatic implant denture.