ObjectiveTo investigate the clinical characteristics and risk factors of Mycoplasma pneumoniae pneumonia （MPP） in children based on a dual classification integrating imaging features and clinical severity. MethodsMedical records of 2 054 pediatric patients with MPP were retrospectively analyzed. The cohort was stratified into severe consolidation （n=253）， severe non-consolidation （n=118）， non-severe consolidation （n=393）， and non-severe non-consolidation groups （n=1 290） based on clinical and radiological findings. Inter group data and characteristics were compared and multiple regression analysis was conducted to construct a prediction model for severe consolidation group. ResultsSignificant differences were observed among the groups in terms of age， duration of fever， length of hospital stay， presence of pulmonary rales， inflammatory markers ［C-reactive protein （CRP） and lactate dehydrogenase （LDH）］， the use of hormones， and bronchoscopic treatment （all P < 0.05）. Compared with the severe non-consolidation group， non-severe consolidation group， and non-severe non-consolidation group， children in severe consolidation group exhibited the longest duration of fever ［8 （6， 11） days vs 6 （2， 9）， 7 （6， 9） and 6 （3， 8） days， respectively］ and the longest length of hospital stay ［7 （5， 8） days vs 6 （5， 8）， 6 （5， 8） and 6 （4， 7） days， respectively］. They also had the highest incidence of reduced breath sounds ［34 cases （13.4%） vs 2 cases （1.7%）， 29 cases （7.4%） and 13 cases （1.0%）， respectively］ and a substantially higher rate of coinfections， particularly viral infections ［63 cases （24.9%） vs 23 cases （19.5%）， 60 cases （15.3%） and 190 cases （14.7%）， respectively］. Multivariate analysis indicated that the independent risk factors for severe MPP （SMPP） were age > 4.5 years， length of hospital stay > 6.5 days， reduced breath sounds， neutrophil-to-lymphocyte ratio （NLR） > 1.66， LDH > 370.5 U/L， CRP > 9.5 mg/L， and coinfection with viruses. Reduced breath sounds （OR = 5.58， 95% CI： 2.45 - 12.69） and coinfection with bacteria （OR = 3.11， 95% CI： 1.43 - 6.75） were identified as the most significant risk factors for pulmonary consolidation in non-severe MPP children. Additionally， reduced breath sounds， coinfection with viruses， LDH > 365.5 U/L， and CRP > 32.1 mg/L were risk factors for severe pneumonia in children with pulmonary consolidation. For non-consolidation MPP children， the presence of pulmonary dry rales （OR = 2.28， 95% CI： 1.46 - 3.56） was the primary independent risk factor for the development of severe pneumonia. ConclusionThe chest imaging findings of MPP are associated with clinical severity， and the risk factor model constructed based on this imaging-clinical classification can assist in achieving precise hierarchical diagnosis and treatment in clinical practice.

Computational approaches, encompassing both physics-based and machine learning (ML) methodologies, have gained substantial traction in drug repurposing efforts targeting specific therapeutic entities. The human dopamine (DA) transporter (hDAT) is the primary therapeutic target of numerous psychiatric medications. However, traditional hDAT-targeting drugs, which interact with the primary binding site, encounter significant limitations, including addictive potential and stimulant effects. In this study, we propose an integrated workflow combining virtual screening based on weighted holistic atom localization and entity shape (WHALES) descriptors with in vitro experimental validation to repurpose novel hDAT-targeting drugs. Initially, WHALES descriptors facilitated a similarity search, employing four benztropine-like atypical inhibitors known to bind hDAT's allosteric site as templates. Consequently, from a compound library of 4,921 marketed and clinically tested drugs, we identified 27 candidate atypical inhibitors. Subsequently, ADMETlab was employed to predict the pharmacokinetic and toxicological properties of these candidates, while induced-fit docking (IFD) was performed to estimate their binding affinities. Six compounds were selected for in vitro assessments of neurotransmitter reuptake inhibitory activities. Among these, three exhibited significant inhibitory potency, with half maximal inhibitory concentration (IC₅₀) values of 0.753 μM, 0.542 μM, and 1.210 μM, respectively. Finally, molecular dynamics (MD) simulations and end-point binding free energy analyses were conducted to elucidate and confirm the inhibitory mechanisms of the repurposed drugs against hDAT in its inward-open conformation. In conclusion, our study not only identifies promising active compounds as potential atypical inhibitors for novel therapeutic drug development targeting hDAT but also validates the effectiveness of our integrated computational and experimental workflow for drug repurposing.

Computational approaches,encompassing both physics-based and machine learning(ML)methodolo-gies,have gained substantial traction in drug repurposing efforts targeting specific therapeutic entities.The human dopamine(DA)transporter(hDAT)is the primary therapeutic target of numerous psychi-atric medications.However,traditional hDAT-targeting drugs,which interact with the primary binding site,encounter significant limitations,including addictive potential and stimulant effects.In this study,we propose an integrated workflow combining virtual screening based on weighted holistic atom localization and entity shape(WHALES)descriptors with in vitro experimental validation to repurpose novel hDAT-targeting drugs.Initially,WHALES descriptors facilitated a similarity search,employing four benztropine-like atypical inhibitors known to bind hDAT's allosteric site as templates.Consequently,from a compound library of 4,921 marketed and clinically tested drugs,we identified 27 candidate atypical inhibitors.Subsequently,ADMETlab was employed to predict the pharmacokinetic and toxi-cological properties of these candidates,while induced-fit docking(IFD)was performed to estimate their binding affinities.Six compounds were selected for in vitro assessments of neurotransmitter re-uptake inhibitory activities.Among these,three exhibited significant inhibitory potency,with half maximal inhibitory concentration(IC50)values of 0.753 μM,0.542 μM,and 1.210 μM,respectively.Finally,molecular dynamics(MD)simulations and end-point binding free energy analyses were con-ducted to elucidate and confirm the inhibitory mechanisms of the repurposed drugs against hDAT in its inward-open conformation.In conclusion,our study not only identifies promising active compounds as potential atypical inhibitors for novel therapeutic drug development targeting hDAT but also validates the effectiveness of our integrated computational and experimental workflow for drug repurposing.

Objective To analyze the situation of blood lipid and blood routine parameters in patients with pneumoconiosis,and construct a column chart diagnostic model to explore their diagnostic value for pneumo-coniosis.Methods A total of 456 patients with pneumoconiosis admitted to the First Affiliated Hospital of Chongqing Medical and Pharmaceutical College from January 2022 to January 2024 were selected as the pneu-moconiosis group,while 462 healthy subjects exposed to dust during the same period were chosen as the con-trol group.Serum lipids and blood routine parameters related to pneumoconiosis were measured and compared between two groups.Univariate and multivariate Logistic regression analyzes were conducted to examine ser-um lipids and blood routine parameters associated with pneumoconiosis.A risk prediction model was construc-ted using logistic regression in machine learning,and the diagnostic efficacy of the column chart diagnostic model was evaluated by calculating the C-index through receiver operating characteristic(ROC)curve and plotting the model calibration curve based on Hosmer Lemeshow goodness of fit.Decision curve analysis(DCA)was used to assess the clinical practicality of the column chart diagnostic model.Results The levels of serum high-density ester protein cholesterol(HDL-C),cholesterol(TC),red blood cell(RBC),hematocrit(HCT),hemoglobin concentration(HGB),lymphocyte number(LYM),and lymphocyte percentage(LYM％)in the pneumoconiosis group were lower than those in the control group(P＜0.05).The levels of neutrophil-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),and systemic immune inflammation index(SII)were higher than those in the control group(P＜0.05).Multivariate Logistic regression analysis showed that HDL-C,LYM％,PLR,and SII were independent influencing factors for pneumoconiosis(P＜0.05).A column chart diagnostic model for the occurrence of pneumoconiosis was constructed using HDL-C,TC,LYM％,PLR,and SII as diagnostic factors.The ROC curve C-index of the diagnostic model was 0.84(95％CI:0.81-0.86),with sensitivity for diagnosing pneumoconiosis of 75.29％,specificity of 77.51％,posi-tive predictive value of 83.25％,and negative predictive value of 67.88％.Internal validation was conducted on the constructed column chart diagnostic model,with a validation set ROC curve C-index of 0.84(95％CI:0.80-0.87),sensitivity of 80.91％,specificity of 72.62％,positive diagnostic value of 79.46％,and negative diagnostic value of 74.39％.The calibration positive curve slope of the diagnostic model was close to 1,and in the fit test P＞0.05.DCA analysis showed that the diagnostic model had clinical practical value for risk diag-nosis of pneumoconiosis.Conclusion HDL-C,TC,LYM％,PLR and SII are independent influencing factors for pneumoconiosis.A column chart diagnostic model for the occurrence of pneumoconiosis is successfully constructed based on machine learning principles,and it has been verified to have high diagnostic efficiency.

Objective To systematically review the efficacy and safety of the tislelizumab combined with anlotinib regimen for advanced non-small-cell lung cancer(NSCLC)patients.Methods PubMed,Embase,Cochrane Library,Web of Science,CNKI,WanFang Data databases were electronically searched to collect clinical studies on the combination of trastuzumab and anlotinib in the treatment of advanced NSCLC patients from inception to August 10,2024.Two reviewers independently screened literature,extracted data and assessed the risk of bias of the included studies.Meta-analysis was then performed by using RevMan 5.4.1 software.Results A total of 6 articles of 468 patients were included,involving 4 randomized controlled trials and 2 prospective cohort studies.Meta-analysis showed that the tislelizumab combined with anlotinib group had higher ORR[OR=2.53,95％CI(1.62,3.93),P＜0.001]and DCR[OR=4.45.95％CI(2.43,8.15),P＜0.001]than the anlotinib group.The CYFRA21-1 level in the combination group was significantly lower than that in the anlotinib group[SMD=-1.07,95％CI(-1.63,-0.51),P＜0.001].For safety,there were no significant differences in the incidence of adverse reaction of leukopenia[OR=0.91,95％CI(0.39,2.14),P=0.83],liver/kidney dysfunction[OR=1.16,95％CI(0.39,3.44)P=0.78].The descriptive analysis results indicated that there was no statistically significant difference in CEA levels between the two groups before treatment in each study(P＞0.05),and the CEA levels in the combination therapy group were lower than those in the anlotinib group after treatment(P＜0.05).Conclusion Compared to anlotinib alone,tislelizumab combined with anlotinib improves ORR,DCR,and reduces tumor markers in NSCLC patients,with comparable incidence of adverse reactions.Due to the limited quality and quantity of the included studies,more high quality studies are needed to verify the above conclusion.

Objective To systematically review the efficacy and safety of the tislelizumab combined with anlotinib regimen for advanced non-small-cell lung cancer(NSCLC)patients.Methods PubMed,Embase,Cochrane Library,Web of Science,CNKI,WanFang Data databases were electronically searched to collect clinical studies on the combination of trastuzumab and anlotinib in the treatment of advanced NSCLC patients from inception to August 10,2024.Two reviewers independently screened literature,extracted data and assessed the risk of bias of the included studies.Meta-analysis was then performed by using RevMan 5.4.1 software.Results A total of 6 articles of 468 patients were included,involving 4 randomized controlled trials and 2 prospective cohort studies.Meta-analysis showed that the tislelizumab combined with anlotinib group had higher ORR[OR=2.53,95％CI(1.62,3.93),P＜0.001]and DCR[OR=4.45.95％CI(2.43,8.15),P＜0.001]than the anlotinib group.The CYFRA21-1 level in the combination group was significantly lower than that in the anlotinib group[SMD=-1.07,95％CI(-1.63,-0.51),P＜0.001].For safety,there were no significant differences in the incidence of adverse reaction of leukopenia[OR=0.91,95％CI(0.39,2.14),P=0.83],liver/kidney dysfunction[OR=1.16,95％CI(0.39,3.44)P=0.78].The descriptive analysis results indicated that there was no statistically significant difference in CEA levels between the two groups before treatment in each study(P＞0.05),and the CEA levels in the combination therapy group were lower than those in the anlotinib group after treatment(P＜0.05).Conclusion Compared to anlotinib alone,tislelizumab combined with anlotinib improves ORR,DCR,and reduces tumor markers in NSCLC patients,with comparable incidence of adverse reactions.Due to the limited quality and quantity of the included studies,more high quality studies are needed to verify the above conclusion.

Purpose: Achieving high-quality immune reconstitution (IR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is directly associated with the patient’s ability to resist infections, prevent tumor relapses, and suppress graft-versus-host disease (GVHD). The status of CD4 + T cells is critical for reconstituting adaptive immunity after transplantation; however, the patterns of reconstitution and their influencing factors remain unclear. Methods: This retrospective cohort study involved 164 patients who underwent myeloablative allo-HSCT from April 2016 to May 2023. Based on the early post-transplantation CD4 + T cell counts, the cohort was divided into two groups: 73 patients with high-quality IR (HIR) and 34 patients with low-quality IR (LIR). LIR was associated with an increased risk of Epstein–Barr virus (EBV) reactivation following transplantation. Plasma EBV viral load was monitored weekly using quantitative PCR for the first 100 days post-transplantation. Results: The LIR group had a higher viral load at the time of the first EBV reactivation and a significantly earlier first reactivation compared to the HIR group. No significant differences were observed in overall survival, GVHD incidence, or relapse rates between the groups. A CD4 + T cell count of < 60 cells/μL within 30 days post-transplantation was associated with a higher incidence of EBV viremia compared to the control group. Conclusion These findings suggest that early CD4 + T cell counts may serve as a predictive marker for post-transplant EBV infection.

FLASH radiotherapy is moving from animal experiments to clinical trials. However, the research on radiation shielding of FLASH radiotherapy rooms has been still in the initial stage. This paper analyses the structural characteristics of the beam pulse of FLASH radiotherapy devices of different technical routes, and discusses the radiation shielding challenges facing the radiotherapy room from FLASH radiotherapy technology based on the current protection standards for the radiotherapy room at home and abroad. The purpose is to provide input to the research on radiation protection of FLASH radiotherapy and to promote the clinical development of FLASH radiotherapy.

FLASH radiotherapy is moving from animal experiments to clinical trials. However, the research on radiation shielding of FLASH radiotherapy rooms has been still in the initial stage. This paper analyses the structural characteristics of the beam pulse of FLASH radiotherapy devices of different technical routes, and discusses the radiation shielding challenges facing the radiotherapy room from FLASH radiotherapy technology based on the current protection standards for the radiotherapy room at home and abroad. The purpose is to provide input to the research on radiation protection of FLASH radiotherapy and to promote the clinical development of FLASH radiotherapy.

Objective:To document any effect of combining transcranial magnetic stimulation (rTMS) with peripheral magnetic stimulation (rPMS) to relieve shoulder pain in hemiplegic stroke survivors.Methods:Sixty hemiplegic stroke survivors with shoulder pain were randomly divided into a Central Group ( n=20), a Peripheral Group ( n=20), and a Combined Group ( n=20). In addition to routine pharmacological intervention and rehabilitation training, the Central Group received 10Hz rTMS over the M1 area of the affected hemisphere, the Peripheral Group received 20Hz rPMS at Erb′s point of the affected limb, while the Combined Group received rTMS followed by rPMS. Before as well as after 2 and 4 weeks of treatment, all were assessed using a numerical pain intensity rating scale (NRS), for passive range of motion (PROM) of the shoulder joint, and using the Fugl-Meyer upper extremity assessment (FMA). Results:Before the treatment there were no significant differences among the 3 groups. After 2 weeks there was significant improvement in the average shoulder PROM and FMA scores, and a significant decrease in the average NRS ratings. After 4 weeks there was continued significant improvement. After 2 and 4 weeks, the Combined Group gave significantly lower NRS ratings than the others and had greater average shoulder PROM improvement. The average FMA score of the Combined Group (36.10±13.32) after two weeks was significantly better than those of the Central and Peripheral groups. However, no significant differences were found between the Central and Peripheral Groups in the other measurements.Conclusions:Both rTMS and rPMS can relieve shoulder pain and promote the recovery of motor function, with superior synergistic effects observed in their combined application.