Purpose To investigate the sex differences of white matter damage in Alzheimer's disease(AD)and their association with cognitive impairment.Materials and Methods This retrospective study included 88 AD patients(48 females),71 amnestic mild cognitive impairment(aMCI)patients(39 females),and 95 healthy controls(63 females)recruited from the Memory Disorder Clinic at the First Affiliated Hospital of Anhui Medical University from September 2017 to July 2024.High-resolution three-dimensional T1 structure images and diffusion tensor imaging images were all obtained from each participant.The mean diffusivity(MD)and fractional anisotropy(FA)values of each white matter region were obtained,and the two-way ANOVA analysis was conducted to investigate brain regions with interaction effects between groups and sexes,those brain regions were then chosen as regions of interest for further correlation analysis with a series of cognitive scale scores.Results In terms of FA values,the right posterior corona radiata,right anterior limb of the internal capsule and left corticospinal tract showed interaction between sexes and cognitive groups(F=4.764,3.812,5.937,all P<0.05).The FA value of AD group was significantly lower than that of healthy control and aMCI group(all P<0.05),but there was no significant difference between healthy control and aMCI group(except the right anterior limb of the internal capsule,P=0.018).In AD group,FA values were significantly higher in women than in men in the previously described brain regions(all P<0.05),while there was no significant difference in FA values between male and female in healthy control and aMCI groups(except the left corticospinal tract,P<0.001).In terms of MD values,the right anterior limb of the internal capsule,right superior corona radiata and left external capsule showed interaction effect between sexes and cognitive groups(F=8.581,3.680,7.218,all P<0.05).The MD value of AD group was significantly higher than that of aMCI group(P<0.001),and aMCI group was higher than that of healthy control group(all P<0.05).In AD group,the MD values in the above brain regions were significantly higher in males than those in females(all P<0.01),while no significant difference was found between males and females in healthy control and aMCI groups(except for the left external capsule,P<0.05).For correlation analysis,the AD group was dimidiated into two groups by sex,the scores of the Montreal cognitive assessment,the Mini Mental state examination and the verbal fluency test of the female patient group were positively correlated with the FA values of the right posterior corona radiate(r=0.372,P=0.009;r=0.345,P=0.016;r=0.383,P=0.007),while the Mini Mental state examination and the verbal fluency test scores of female AD patient group were negatively correlated with the MD values of the right superior corona radiata(r=-0.360,P=0.012;r=-0.360,P=0.003).Conclusion Compared to the healthy control and MCI groups,white matter damage in AD patients shows sex differences and is associated with general cognitive and language functions impairment in female AD patients.

The objective of this study was to evaluate the toxicity and safety of novel Mycobacterium tuberculosis fusion strain protein derivatives,referred to as B/R strain active proteins.In cellular experiments,RAW264.7 cells were treated with each vaccine preparation,and apoptosis rates were measured.In subsequent animal experiments,C57BL/6 mice were immunized via subcutaneous injection,and their survival and body weight changes were monitored and recorded at 2,4,8,12,and 16 weeks.The lungs and spleens were harvested to calculate organ coefficients,and pathological examinations were conducted.At the eighth week of immunization,the mice were infected with high concentrations of BCG,and pathological changes in the lungs and spleens were observed 4 weeks post-infection.The apoptosis rate at 6 hours was significantly higher in the experimental group than the PBS group(P<0.05).At 12 and 24 hours,the apoptosis rate in the experimental group remained higher than that in the PBS group,although this difference was not statistically significant.After immunization,mice in all four groups exhibited normal growth patterns,as indicated by stable body weight changes.At 4 and 12 weeks post-immunization,the lung coefficients in the protein group were significantly higher than those in the PBS group at the same time points.Additionally,the lung coefficients in the BCG group were significantly elevated across all time periods(P<0.05).The spleen coefficients in the protein and BCG groups were significantly higher than those in the PBS group at 2,4,8,12,and 16 weeks,whereas the ICD B/R group showed higher spleen coefficients than the PBS group only at week 8(P<0.05).Pathological examination revealed normal lung and spleen tissues in the PBS group.However,during the 2-8 weeks immunization period,lung and spleen tissues in all experimental groups exhibited varying degrees of damage,which gradually diminished by 12-16 weeks.Notably,no tuberculosis nodules were observed in any experimental group.After infection with high concentrations of BCG,no overt pathological changes were observed on the surfaces of the lungs and spleens in any group.Microscopic examination revealed less severe pathological changes in the lungs and spleens of mice in the experimental groups than the PBS group.Furthermore,no statistically significant differences were observed between the protein group and the BCG group.Our findings suggested that the B/R strain active proteins'toxicity and safety profiles were comparable to those of BCG,and showed immunoprotective effects.This study provides an experimental foundation for the development of a novel tuberculosis vaccine.

Objective To investigate the role of Sneathia sanguinegens(S.sanguinegens)in the development of unexplained recurrent spontaneous abortion(URSA).Methods A case-control study was conducted to analyze the vaginal flora characteristics of 65 patients with URSA and 18 healthy controls through 16S rRNA gene sequencing.Toxicity profile of S.sanguinegens on human cervical cancer cells(ME-180),human umbilical vein endothelial cells(HUVEC)and human placental choriocarcinoma cells(JEG-3)was analyzed at the cellular level to assess the mechanism of it in adverse pregnancy outcomes.And S.sanguinegens was used to infect C57BL/6J mice to explore the toxic effect on living organisms.Results The relative abundance of Sneathia was increased in patients with URSA compared with healthy controls.It was positively correlated with the number of miscarriages,and was attributed to S.sanguinegens.We also found that S.sanguinegens damaged ME-180,JEG-3 and HUVEC cells.The degree of cellular damage was related to the level of S.sanguinegens added.Intravenous infection with S.sanguinegens caused inflammatory damage in several organs and extramedullary hematopoiesis in the spleen.Conclusion S.sanguinegens is closely related to URSA and should be emphasized in patients with high vaginal bacterial load.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To evaluate the influence of different positive end-expiratory pressure on the ventilation of laryngeal mask airway in pediatric patients undergoing laparoscopic surgery through ultrasound assessment.Methods:In this randomized controlled trial, 90 pediatric patients of both sexes, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, aged 2-10 yr, with a body mass index of 12-22 kg/m 2, scheduled for elective laparoscopic surgery, were divided into 3 groups ( n=30 each) by a random number table method: group P0, group P3, and group P5. Each group adopted the pressure-controlled mode with an inspiration/expiration ratio of 1∶2, a flow rate of 2 L/min, and a respiratory rate of 16-26 breaths/min. The positive end-expiratory pressure was set at 0, 3 and 5 cmH 2O(1 cmH 2O=0.098 kPa) in P0, P3 and P5 groups respectively. The ultrasonic scores and misalignment rate of the laryngeal mask airway were recorded every 5 min following the pneumoperitoneum, and the occurrence of intraoperative hypoxemia (SpO 2 < 92%) and P ETCO 2 ≥ 45 mmHg(1 mmHg=0.133 kPa) was recorded. The development of hypoxemia, blood staining on the laryngeal mask airway and hoarseness after laryngeal mask airway removal were also recorded. Results:Compared with P0 group, the ultrasound scores were significantly increased at 15 min of pneumoperitoneum in P3 group ( P<0.05), and the ultrasound scores and the laryngeal mask airway misplacement rate were significantly increased, and no significant change was found in the other parameters in P5 group ( P<0.05). There were no statistically significant differences in each parameter between P5 group and P3 group ( P>0.05). There was no statistically significant difference in the incidence of postoperative complications among the three groups ( P>0.05). Conclusions:The laryngeal mask airway provides better ventilatory effect in pediatric patients undergoing laparoscopic surgery when the PEEP is set at 3 cmH 2O.

Objective:To evaluate the accuracy of respiratory variation in carotid artery blood flow peak velocity (ΔVpeak-CA) combined with tidal volume challenge (TVC) test in predicting fluid responsiveness of patients receiving lung-protective ventilation.Methods:Eighty American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients of either sex, aged 18-80 yr, with a body mass index of 18-30 kg/m 2, undergoing elective open abdominal surgery with general anesthesia, were selected. Lung-protective strategies were used during surgery: FiO 2 40%, tidal volume (V T) 6 ml/kg (ideal body weight), personalized positive end-expiratory pressure. TVC was conducted at 5 min after hemodynamic stabilization following intubation (T 1): V T was adjusted from 6 ml/kg to 8 ml/kg, lasting for 1 min (T 2), and then V T was decreased to 6 ml/kg. Ultrasound was used to measure ΔVpeak before and after TVC test, and ΔVpeak-CA was calculated. Volume expansion was conducted at 5 min after TVC test, and an increase in cardiac index (△CI≥15%) after volume expansion was considered as positive fluid responsiveness. The patients were divided into fluid responsiveness group (R group) and non-responsiveness group (NR group). The receiver operating characteristic curve was plotted and the area under the receiver operating characteristic curve (AUC) was calculated to evaluate the efficiency of ΔVpeak-CA at T 1 (ΔVpeak-CA T 1), ΔVpeak-CA at T 2 (ΔVpeak-CA T 2) and the difference in ΔVpeak-CA between T 1 and T 2 (ΔVpeak-CA T 2-T 1) in predicting fluid responsiveness. Results:Seventy-three patients were finally included in this study, with 45 in R group and 28 in NR group. The AUC of ΔVpeak-CA T 2 in predicting fluid responsiveness was 0.880, with the sensitivity of 0.778 and the specificity of 0.857, and the optimum cut-off value was 14.5%. The AUC of ΔVpeak-CA T 2-T 1 in predicting fluid responsiveness was 0.876, with the sensitivity of 0.667 and the specificity of 0.964, and the optimum cut-off value was 5.5%, and the AUC of ΔVpeak-CA T 1 in predicting fluid responsiveness was only 0.646. Conclusions:ΔVpeak-CA combined with TVC test can accurately predict fluid responsiveness of patients receiving lung-protective ventilation.

Objective:To evaluate the effect of trans-nasal humidified rapid insufflation ventilatory exchange (THRIVE) on the early postoperative atelectasis in patients undergoing prolonged non-intubated intravenous anesthesia for gastrointestinal endoscopic procedures.Methods:In this randomized double-blind controlled trial, 150 patients of either sex, aged 18-80 yr, with American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ and body mass index of 18-30 kg/m 2, scheduled for endoscopic mucosal resection of multiple colorectal polyps at Northern Jiangsu People′s Hospital Affiliated to Yangzhou University from February 18 to June 15, 2024, were divided into 2 groups ( n=75 each) using simple random allocation: THRIVE group (group T) and conventional oxygen therapy group (group C). In group T, the oxygen flow rate was 10 L/min before anesthesia induction and increased to 50 L/min after induction until the end of operation, and the inhaled oxygen concentration was 100%. Group C used conventional mask oxygen inhalation, with an oxygen flow rate of 10 L/min during anesthesia induction and maintenance. Lung ultrasonography was performed immediately before anesthesia induction and after the end of surgery, and the modified lung ultrasound score and diaphragm mobility during quiet breathing were recorded to assess the occurrence of atelectasis and diaphragmatic dysfunction. The lowest intraoperative SpO 2 value, adverse events during surgery and in the postanesthesia care unit (PACU), duration of PACU stay, adverse events within 7 days after operation, hospitalization duration, and satisfaction scores of both patients and endoscopists were recorded. Results:Compared with group C, the postoperative modified lung ultrasound score and incidence of atelectasis and diaphragmatic dysfunction were significantly decreased, the lowest intraoperative SpO 2 value was increased, the incidence of hypoxemia was decreased, the duration of PACU stay was shortened, and endoscopists′ satisfaction scores were increased ( P<0.05), and no statistically significant changes were observed in diaphragm mobility, incidence of other intraoperative adverse events, incidence of adverse events during PACU stay and within 7 days after operation, or patients′ satisfaction scores in group T ( P>0.05). Conclusions:THRIVE can reduce the risk of early postoperative atelectasis and intraoperative hypoxemia, thereby promoting postoperative recovery of patients undergoing gastrointestinal endoscopy under long-term non-intubated anesthesia.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.