Objective: To explore the impacts of coal mine dust on lung function in rats, so as to provide the basis for the early prevention and treatment of coal worker's pneumoconiosis. Methods: Seventy-two SPF-grade 8-week-old male Sprague-Dawley rats were randomly divided into the coal dust group, the coal-silica dust group, the silica dust group and the control group. The rats in the first three groups of rats were administered 1 mL corresponding dust suspension into the lungs using non-exposure tracheal instillation, while the rats in the control group were administered 1 mL normal saline. Respiratory rate (f), forced vital capacity (FVC), peak expiratory flow (PEF) and dynamic pulmonary compliance (Cdyn) were measured at 1, 3 and 6 months after dust exposure. Lung tissues were collected to measure reactive oxygen species (ROS) and adenosine triphosphate (ATP) levels using corresponding ELISA kits and ATP assay kits, respectively. The relative mRNA expressions of peroxisome proliferators-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial transcription factor A (TFAM) were detected using real-time fluorescent quantitative polymerase chain reaction assay. The relative protein expressions of PGC-1α and TFAM were detected using Western blotting. Results: There was no interaction between dust type and exposure duration on f (P>0.05), but there were interactions on FVC, PEF and Cdyn (all P<0.05). Compared with the control group at 6 months after dust exposure, the f of the rats in the silica dust group were increased, while the FVC and PEF of the rats in the coal-silica dust and silica dust groups were decreased, and Cdyn of the rats in the coal dust, coal-silica dust and silica dust groups were decreased (all P<0.05). There were interactions between dust type and exposure duration on ROS and ATP levels, the relative mRNA and protein expressions of PGC-1α and TFAM (all P<0.05). Compared with the control group at 3 and 6 months after dust exposure, the ROS levels in the rats in the coal dust, coal-silica dust and silica dust groups were increased, while the ATP levels, the relative mRNA and protein expressions of PGC-1α and TFAM were decreased (all P<0.05). Conclusion The lung function impairment in rats caused by different types of coal mine dust is related to PGC-1α-mediated mitochondrial biogenesis dysfunction, which leads to increased ROS levels, decreased ATP and TFAM levels.

Objective:To evaluate the efficacy of eculizumab in treating hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) .Methods:This retrospective study included 11 patients who developed TA-TMA after allogeneic hematopoietic stem cell transplantation and subsequently received eculizumab treatment at Peking University People′s Hospital between June 2018 and May 2024. The incidence of TA-TMA, treatment details, and clinical outcomes were analyzed.Results:Among the 11 included patients [4 males, 7 females; median age: 29 years (range: 9-56) ], underlying diseases were severe aplastic anemia (SAA) in 5 patients, acute lymphoblastic leukemia (ALL) in 3 patients, and acute myeloid leukemia (AML) in 3 patients. The median time to TA-TMA diagnosis was 48 days post-transplantation (range: 4-213 days), and all patients met the diagnostic criteria for high-risk TA-TMA. The median interval from TA-TMA diagnosis to the initiation of eculizumab treatment was 12 days (range: 1-56 days). Patients received a median of 3 doses of eculizumab (range: 1-14). Ten of the 11 patients were assessed as having no response (NR) to eculizumab at the end of treatment or at death. One patient achieved a partial response (PR) but subsequently died after TA-TMA relapsed due to infection. At the last follow-up, all patients were either lost to follow-up or had died. The median follow-up duration was 88 days (range: 33-326 days), and the median time from TA-TMA diagnosis to the last follow-up was 31 days (range: 21-113 days) .Conclusion:Eculizumab demonstrated poor efficacy in this TA-TMA cohort. This might be attributable to the critical and complex condition of the patients, delayed initiation of eculizumab treatment, and insufficient dosage.

Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.

People with AIDS are highly prone to opportunistic infections,among which pulmonary infections are the most common,with high incidence and fatality rates.How to effectively prevent or reduce the occurrence of HIV-related lung infections(HRLI)is of great practical significance.From the perspective of traditional Chinese medicine(TCM),HRLI and AIDS share common pathological mechanisms,including qi deficiency,spleen defi-ciency,phlegm-heat or phlegm-dampness obstructing the lungs.Based on the TCM theory of"preventing disease before it occurs",the three-level prevention approach includes:the first step"preventing disease before it occurs"emphasizes strengthening the body's defense mechanisms by tonifying the spleen and benefiting qi,and nourishing the lungs and kidneys to strengthen the exterior and protect the body;the second step"preventing the progression of disease once it occurs"emphasizes the removal of pathogenic factors while strengthening the body's defenses.Based on the principles of syndrome differentiation and treatment in TCM,focuses are kept on the spleen tonifying and phlegm resolving,pathogenic factors dispelling and dampness eliminating,while protecting the spleen and nourishing other organs.The third step"preventing relapse after recovery"emphasizes replenishing deficiencies and enhancing immunity.Adopting the three-level prevention approach and early intervention can reduce the inci-dence of HRLI,which is a new idea for the prevention and treatment of HRLI with TCM.

Objective The study aimed to investigate the predictive efficacy of contrast-enhanced ultrasound combined with telomerase reverse transcriptase(TERT)promoter mutation in constructing nomogram model for the prediction of concomitant cervical lymph node metastasis(CLNM)in papillary thyroid microcarcinoma(pTMC).Methods A total of 202 patients with pTMC who underwent partial or total thyroidectomy+lymph node dissection at our hospital from January 2021 to March 2024 were selected.Then,they were divided into the CLNM group(97 patients)and the non-CLNM group(105 patients)according to whether they had concomitant CLNM on postoperative pathological examination.General data and ultrasound(conventional ultrasound and contrast-enhanced ultrasound)characteristics were collected from all patients with pTMC,and Sanger sequencing was used to detect TERT promoter mutations.The influencing factors of pTMC complicated by CLNM were analyzed by single-factor and multifactorial unconditional logistic regression;the nomogram model of pTMC complicating CLNM with contrast-enhanced ultra-sound combined with TERT promoter mutation was constructed by RStudio 4.4.1 software,and the consistency and net benefit of the nomogram model were evaluated by using calibration curves,decision curves,and C-indexes,and the Hosmer-Lemeshow test for goodness of fit of the nomogram model;The predictive efficiency of the nomogram model constructed by combining contrast-enhanced ultrasound and TERT promoter mutation for pTMC complicated by CLNM was evaluated by plotting receiver operating characteristic(ROC)curves using MedCalc22.023 software.Results After postoperative pathological examination,the incidence of CLNM in 202 patients with pTMC was 48.02%(97/202).Univariate analysis showed that thyroglobulin antibodies,number of lesions,aspect ratio,micro-calcifications,enhancement time,enhancement mode,enhancement intensity,capsular continuity,and TERT promoter mutations were associated with pTMC complicating CLNM(P<0.05).Multifactorial unconditional logistic regression showed that multifocal tumours(OR=3.487,95%CI:1.641～7.406,P=0.001),microcalcifications(OR=4.484,95%CI:2.113～9.516,P<0.001),equal or high enhancement(OR=3.187,95%CI:1.460～6.957,P=0.004),disruption of peritoneal continuity(OR=2.201,95%CI:1.051～4.608,P=0.036),and TERT promoter mutation positivity(OR=4.460,95%CI:2.132～10.103,P<0.001)were the independent risk factors for pTMC complicating CLNM.A contrast-enhanced ultrasound combined TERT promoter mutation nomogram model was constructed based on independent risk factors for pTMC complicating CLNM[Logit(p)=-4.486+1.350×number of foci+1.399×microcalcifications+2.124×intensity of enhancement+1.524×capsular continuity+2.175×TERT promoter mutations].The C-index of this nomogram model was 0.899(95%CI:0.893～0.905),the calibra-tion curve alignment was close to the ideal curve,the decision curve was higher than the two extreme curves,and the Hosmer-Lemeshow test showed a P>0.05.The ROC curve analysis showed that the nomogram model constructed with contrast-enhanced ultrasound combined with TERT promoter mutations predicted CLNM in pTMC with an area under the curve of 0.899.This was significantly higher than the area under the curves for contrast-enhanced ultra-sound alone(0.857)and TERT promoter mutations alone(0.697)(P<0.05).Conclusion The contrast-enhanced ultrasound combined with TERT promoter mutations to construct a nomogram model has high predictive efficiency for pTMC complicating CLNM.

Sj?gren's syndrome(SS)is one of the common rheumatic diseases in clinical practice.Modern medicine commonly uses drugs such as artificial tears,saliva,glucocorticoids,immunosuppressants,and biologics to control the condition.Clinical practice has shown that in addition to modern medical basic treatment,the use of traditional Chinese medicine(TCM)can help improve the clinical efficacy of SS.According to the symptoms and signs of Sj?gren's syndrome in TCM,it is classified as"dryness and obstruction",and the core pathogenesis of the disease is spleen deficiency and deficiency of body fluids.Subsequently,toxic and pathogenic factors gather,leading to the decline of internal organs.The initial causes are spleen damage,unstable barrier,and invasion of pathogenic factors.The core link is spleen dysfunction,insufficient body fluid,and dryness arising from it.Spleen deficiency generates evil,obstruction of qi,and lack of body fluids are the root causes of illness.The main treatment method is the"spleen strengthening method",which treats spleen deficiency,dampness and stagnation,and the body fluid is not distributed.The treatment focuses on strengthening the spleen and qi,supplementing the lungs and generating fluids.Spleen deficiency leads to loss of vitality,blood stasis obstructs blood vessels,and the treatment is to strengthen the spleen,soothe the liver,remove blood stasis,and unblock the orifices.The spleen yang is not vigorous,and qi transformation is impaired.The treatment is to invigorate the spleen and warm the stomach,promote yang circulation,and promote diuresis.

Objective:To explore the effect of social cognition and interaction training (SCIT) combined with transcranial magnetic stimulation (TMS) on intrinsic motivation and social cognition in patients with schizophrenia.Methods:Forty-two stable schizophrenia patients were randomly divided into the SCIT + TMS group( n=22) and the SCIT group( n=20). All the subjects received 20 sessions of SCIT treatment, and the SCIT+ TMS group simultaneously received 15 sessions of intermittent theta burst stimulation(iTBS) over the left dorsolateral prefrontal cortex(DLPFC). All the subjects were assessed by intrinsic motivation inventory for schizophrenia research(IMI-SR), Chinese version of the ambiguous intentions hostility questionnaire(AIHQ-C), theory of mind-picture sequencing task(ToM-PST), mentalization scale (MentS), Chinese version of interpersonal reactivity index (IRI-C) and positive and negative syndrome scale (PANSS) before and after intervention. SPSS 26.0 software was used for data analysis.Wilcoxon signed-rank test was used for intra-group comparison before and after treatment, while Mann-Whitney U test and covariance analysis were used for inter-group comparison.Spearman correlation analysis and Logistic regression analyses were used to explore the association between the intrinsic motivation and social cognition. Results:There were no significant differences on IMI-SR scores before and after treatment between the two groups(all P>0.05). In the SCIT+ TMS group, the total score of hostility bias (HB), HB scores in ambiguous scenes, HB scores in intentional scenes, and aggressive bias (AB) scores in ambiguous scenes of AIHQ-C scale after treatment were lower than those befor treatment( Z=-2.044--3.112, all P<0.05), while the total score of ToM-PST(18.50(16.00, 21.00) vs 15.50(11.75, 18.00), Z=-2.598, P=0.009) and IRI-C imagination score (12.18±3.79, 14.41±4.73, t=-2.694, P=0.014) were higher than those before treatment.In the SCIT group, the total score of ToM-PST after treatment was higher than that before treatment(21.00(20.00, 22.00) vs 17.00(14.50, 20.75), Z=-2.518, P=0.012).There was no significant statistical difference in MentS scores between after treatment and before treatment ( P>0.05). The difference in AIHQ-C intentional scenario AB score before and after treatment was higher in the SCIT+ TMS group than in the SCIT group ( Z=-1.996, P=0.046), while there was no statistically significant difference in the difference before and after treatment in social cognitive scores between the two groups (all P>0.05).In the combined two samples, Spearman correlation analysis showed that the total score of IMI-SR before treatment was positively correlated with the primary belief score of ToM-PST understanding, reciprocity score, MentS total score, other person mentalization score, motivation mentalization score, IRI-C total score, viewpoint taking score, and empathy concern score after treatment( r=0.341-0.509, all P<0.05), while negatively correlated with AIHQ-C total score and factor scores ( r=-0.434--0.645, P<0.05).Logistic regression analysis showed that the total score of IMI-SR had negative impact on AIHQ-C total HB score( B=-0.047, OR=0.954, 95% CI=0.917-0.993).The value score had a positive impact on the total score of MentS ( B=0.143, OR=1.154, 95% CI=1.043-1.277), other person mentalization score( B=0.166, OR=1.181, 95% CI=1.058-1.318), motivation mentalization score( B=0.111, OR=1.117, 95% CI=1.021-1.223), IRI-C total score ( B=0.138, OR=1.148, 95% CI=1.038-1.270), and viewpoint taking score( B=0.194, OR=1.214, 95% CI=1.076-1.369). Interest score had a positive impact on IRI-C empathy concern score ( B=0.098, OR=1.103, 95% CI=0.998-1.218) and ToM-PST understanding primary belief score( B=0.130, OR=1.138, 95% CI=1.010-1.283) and reciprocity score( B=0.189, OR=1.208, 95% CI=1.057-1.380). Conclusion:The research results did not confirm the effect of TMS over the DLPFC on enhancing intrinsic motivation, as well as the synergistic effect of SCIT treatment on social cognition. But the correlation results indicates that improving schizophrenia patients' intrinsic motivation level in cognitive training is meaningful for promoting social cognition.

Sj?gren's syndrome(SS)is one of the common rheumatic diseases in clinical practice.Modern medicine commonly uses drugs such as artificial tears,saliva,glucocorticoids,immunosuppressants,and biologics to control the condition.Clinical practice has shown that in addition to modern medical basic treatment,the use of traditional Chinese medicine(TCM)can help improve the clinical efficacy of SS.According to the symptoms and signs of Sj?gren's syndrome in TCM,it is classified as"dryness and obstruction",and the core pathogenesis of the disease is spleen deficiency and deficiency of body fluids.Subsequently,toxic and pathogenic factors gather,leading to the decline of internal organs.The initial causes are spleen damage,unstable barrier,and invasion of pathogenic factors.The core link is spleen dysfunction,insufficient body fluid,and dryness arising from it.Spleen deficiency generates evil,obstruction of qi,and lack of body fluids are the root causes of illness.The main treatment method is the"spleen strengthening method",which treats spleen deficiency,dampness and stagnation,and the body fluid is not distributed.The treatment focuses on strengthening the spleen and qi,supplementing the lungs and generating fluids.Spleen deficiency leads to loss of vitality,blood stasis obstructs blood vessels,and the treatment is to strengthen the spleen,soothe the liver,remove blood stasis,and unblock the orifices.The spleen yang is not vigorous,and qi transformation is impaired.The treatment is to invigorate the spleen and warm the stomach,promote yang circulation,and promote diuresis.

Objective:To explore the effect of social cognition and interaction training (SCIT) combined with transcranial magnetic stimulation (TMS) on intrinsic motivation and social cognition in patients with schizophrenia.Methods:Forty-two stable schizophrenia patients were randomly divided into the SCIT + TMS group( n=22) and the SCIT group( n=20). All the subjects received 20 sessions of SCIT treatment, and the SCIT+ TMS group simultaneously received 15 sessions of intermittent theta burst stimulation(iTBS) over the left dorsolateral prefrontal cortex(DLPFC). All the subjects were assessed by intrinsic motivation inventory for schizophrenia research(IMI-SR), Chinese version of the ambiguous intentions hostility questionnaire(AIHQ-C), theory of mind-picture sequencing task(ToM-PST), mentalization scale (MentS), Chinese version of interpersonal reactivity index (IRI-C) and positive and negative syndrome scale (PANSS) before and after intervention. SPSS 26.0 software was used for data analysis.Wilcoxon signed-rank test was used for intra-group comparison before and after treatment, while Mann-Whitney U test and covariance analysis were used for inter-group comparison.Spearman correlation analysis and Logistic regression analyses were used to explore the association between the intrinsic motivation and social cognition. Results:There were no significant differences on IMI-SR scores before and after treatment between the two groups(all P>0.05). In the SCIT+ TMS group, the total score of hostility bias (HB), HB scores in ambiguous scenes, HB scores in intentional scenes, and aggressive bias (AB) scores in ambiguous scenes of AIHQ-C scale after treatment were lower than those befor treatment( Z=-2.044--3.112, all P<0.05), while the total score of ToM-PST(18.50(16.00, 21.00) vs 15.50(11.75, 18.00), Z=-2.598, P=0.009) and IRI-C imagination score (12.18±3.79, 14.41±4.73, t=-2.694, P=0.014) were higher than those before treatment.In the SCIT group, the total score of ToM-PST after treatment was higher than that before treatment(21.00(20.00, 22.00) vs 17.00(14.50, 20.75), Z=-2.518, P=0.012).There was no significant statistical difference in MentS scores between after treatment and before treatment ( P>0.05). The difference in AIHQ-C intentional scenario AB score before and after treatment was higher in the SCIT+ TMS group than in the SCIT group ( Z=-1.996, P=0.046), while there was no statistically significant difference in the difference before and after treatment in social cognitive scores between the two groups (all P>0.05).In the combined two samples, Spearman correlation analysis showed that the total score of IMI-SR before treatment was positively correlated with the primary belief score of ToM-PST understanding, reciprocity score, MentS total score, other person mentalization score, motivation mentalization score, IRI-C total score, viewpoint taking score, and empathy concern score after treatment( r=0.341-0.509, all P<0.05), while negatively correlated with AIHQ-C total score and factor scores ( r=-0.434--0.645, P<0.05).Logistic regression analysis showed that the total score of IMI-SR had negative impact on AIHQ-C total HB score( B=-0.047, OR=0.954, 95% CI=0.917-0.993).The value score had a positive impact on the total score of MentS ( B=0.143, OR=1.154, 95% CI=1.043-1.277), other person mentalization score( B=0.166, OR=1.181, 95% CI=1.058-1.318), motivation mentalization score( B=0.111, OR=1.117, 95% CI=1.021-1.223), IRI-C total score ( B=0.138, OR=1.148, 95% CI=1.038-1.270), and viewpoint taking score( B=0.194, OR=1.214, 95% CI=1.076-1.369). Interest score had a positive impact on IRI-C empathy concern score ( B=0.098, OR=1.103, 95% CI=0.998-1.218) and ToM-PST understanding primary belief score( B=0.130, OR=1.138, 95% CI=1.010-1.283) and reciprocity score( B=0.189, OR=1.208, 95% CI=1.057-1.380). Conclusion:The research results did not confirm the effect of TMS over the DLPFC on enhancing intrinsic motivation, as well as the synergistic effect of SCIT treatment on social cognition. But the correlation results indicates that improving schizophrenia patients' intrinsic motivation level in cognitive training is meaningful for promoting social cognition.

Objective The study aimed to investigate the predictive efficacy of contrast-enhanced ultrasound combined with telomerase reverse transcriptase(TERT)promoter mutation in constructing nomogram model for the prediction of concomitant cervical lymph node metastasis(CLNM)in papillary thyroid microcarcinoma(pTMC).Methods A total of 202 patients with pTMC who underwent partial or total thyroidectomy+lymph node dissection at our hospital from January 2021 to March 2024 were selected.Then,they were divided into the CLNM group(97 patients)and the non-CLNM group(105 patients)according to whether they had concomitant CLNM on postoperative pathological examination.General data and ultrasound(conventional ultrasound and contrast-enhanced ultrasound)characteristics were collected from all patients with pTMC,and Sanger sequencing was used to detect TERT promoter mutations.The influencing factors of pTMC complicated by CLNM were analyzed by single-factor and multifactorial unconditional logistic regression;the nomogram model of pTMC complicating CLNM with contrast-enhanced ultra-sound combined with TERT promoter mutation was constructed by RStudio 4.4.1 software,and the consistency and net benefit of the nomogram model were evaluated by using calibration curves,decision curves,and C-indexes,and the Hosmer-Lemeshow test for goodness of fit of the nomogram model;The predictive efficiency of the nomogram model constructed by combining contrast-enhanced ultrasound and TERT promoter mutation for pTMC complicated by CLNM was evaluated by plotting receiver operating characteristic(ROC)curves using MedCalc22.023 software.Results After postoperative pathological examination,the incidence of CLNM in 202 patients with pTMC was 48.02%(97/202).Univariate analysis showed that thyroglobulin antibodies,number of lesions,aspect ratio,micro-calcifications,enhancement time,enhancement mode,enhancement intensity,capsular continuity,and TERT promoter mutations were associated with pTMC complicating CLNM(P<0.05).Multifactorial unconditional logistic regression showed that multifocal tumours(OR=3.487,95%CI:1.641～7.406,P=0.001),microcalcifications(OR=4.484,95%CI:2.113～9.516,P<0.001),equal or high enhancement(OR=3.187,95%CI:1.460～6.957,P=0.004),disruption of peritoneal continuity(OR=2.201,95%CI:1.051～4.608,P=0.036),and TERT promoter mutation positivity(OR=4.460,95%CI:2.132～10.103,P<0.001)were the independent risk factors for pTMC complicating CLNM.A contrast-enhanced ultrasound combined TERT promoter mutation nomogram model was constructed based on independent risk factors for pTMC complicating CLNM[Logit(p)=-4.486+1.350×number of foci+1.399×microcalcifications+2.124×intensity of enhancement+1.524×capsular continuity+2.175×TERT promoter mutations].The C-index of this nomogram model was 0.899(95%CI:0.893～0.905),the calibra-tion curve alignment was close to the ideal curve,the decision curve was higher than the two extreme curves,and the Hosmer-Lemeshow test showed a P>0.05.The ROC curve analysis showed that the nomogram model constructed with contrast-enhanced ultrasound combined with TERT promoter mutations predicted CLNM in pTMC with an area under the curve of 0.899.This was significantly higher than the area under the curves for contrast-enhanced ultra-sound alone(0.857)and TERT promoter mutations alone(0.697)(P<0.05).Conclusion The contrast-enhanced ultrasound combined with TERT promoter mutations to construct a nomogram model has high predictive efficiency for pTMC complicating CLNM.