Compared with traditional therapies for chronic liver disease （CLD）， Bifidobacterium has the characteristics of multi-target intervention， high biosafety， and good host compatibility and provides new strategies for intervention of CLD progression in terms of microecological regulation. Various studies have shown that Bifidobacterium regulates liver homeostasis and exerts a therapeutic effect on CLD by regulating intestinal flora， maintaining antioxidation， promoting energy consumption， alleviating inflammation， improving glycolipid metabolism， and exerting an antitumor effect. This article systematically reviews the studies on Bifidobacterium in the treatment of CLD in China and globally， explores their different mechanisms， and elaborates on the interaction between related signaling pathways （such as the nuclear factor erythroid 2-related factor 2 signaling pathway and the adenosine monophosphate-activated protein kinase signaling pathway） and the liver， in order to provide a basis for probiotic intervention in liver pathology， as well as new ideas for the comprehensive treatment of CLD.

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: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.

The contents recorded in the rotation registration manual is not only the quantitative indicators for evaluating the quality of residency training, but also the important basis for training assessment and issuance of training certificates. In order to solve the problems of data authenticity, information delay, and repeated entry in the rotation registration manual for residency training, Shanghai East Hospital, Tongji University, launched a project to dock the electronic rotation registration manual with the hospital information system. Through the establishment of the project team, the development of working mechanisms, and the implementation of the project, data analysis was used for process reformation and system optimization, so as to continuously improve management efficiency and medical safety while solving problems and form a set of implementation system with reference significance in practice.

Objective To investigate the diagnostic value of three-dimensional power Doppler ultrasound(3D-PDUS)in fetal growth restriction(FGR).Methods A total of 120 pregnant women in the third trimester who were given birth in Wenzhou People's Hospital from September 2021 to December 2023 were selected as study objects,50 pregnant women with FGR confirmed by clinical and ultrasound were included in case group,and 70 pregnant women with normal fetal development were included in control group.The renal volume and renal blood flow parameters of the fetuses in two groups were compared.The pregnancy outcomes and perinatal conditions of two groups were compared.Receiver operating characteristic(ROC)curve was plotted to calculate the area under the curve(AUC),and the diagnostic efficacy of various blood flow parameters for FGR was evaluated.Results The renal volume/gestational week,renal vascularization index,vascularization flow index and renal artery peak systolic velocity of the fetuses in case group were significantly lower than those in control group,while renal artery peak systolic velocity/end diastolic velocity,pulsation index and resistance index were significantly higher than those in control group(P＜0.05).There was no significant difference in renal flow index between two groups(P＞0.05).ROC curve results showed that the diagnostic efficacy of renal volume/gestational week and renal artery peak systolic velocity were higher,while the diagnostic efficacy of combined application was the highest,with an AUC of 0.89.The rate of low birth weight infants in case group was significantly higher than that in control group,and neonatal Apgar score was significantly lower than that in control group(P＜0.01).Conclusion 3D-PDUS quantitative analysis parameters evaluated renal volume and blood perfusion could predict FGR,which is conducive to early diagnosis of FGR and guide clinical intervention,and effectively reduce adverse pregnancy outcomes.

Objective To explore the clinical characteristics of drug-induced liver injury(DILI),and provide reference for early clinical recognition,diagnosis and treatment of DILI.Methods Clinical datas of 65 patients with DILI hospitalized in the First Affiliated Hospital of Guangxi University of Chinese Medicine from January 2019 to December 2023 were retrospectively analyzed,and their general conditions,using drugs,distribution type of liver injury,traditional Chinese medicine treatment and outcome were statistically analyzed.Results A total of 65 patients were included,including 27 males and 38 females,with an average age of(46.40±19.19)years old.The majority of patients were 41 to 60 years old.Chinese herbal medicine and Chinese patent medicine accounted for the highest proportion of drugs inducing DILI(30.8％).Hepatocyte injury was the most common type of DILI,with 39 cases.The main clinical manifestations of DILI patients were fatigue,abdominal discomfort,aversion to oil,yellow eyes,yellow urine and so on.In the treatment of traditional Chinese medicine,liquorice root was the most frequently used,with a frequency of 60.7％.After active treatment,59 patients were cured and discharged from hospital.Conclusion Hepatocyte injury is the main type of DILI.Clinical monitoring of hepatotoxicity of traditional Chinese herbal medicine and Chinese patent medicine should be strengthened to reduce the damage to liver caused by adverse drug reactions.

Conventional administration methods have problems including low bioavailability, complex operation process, and discomfort of patients with fear of needles. Transdermal delivery can avoid these problems, whereas most drugs are difficult to directly penetrate the skin cuticle and reach the diseased site. Microneedling is an emerging method of local drug delivery, enabling the drug penetration through the stratum corneum of the skin in a minimally invasive manner and delivering the drug directly to the diseased site, thereby improving the treatment effect. Stimuli-responsive microneedles have attracted much attention because of the spatiotemporal controllability, high drug delivery efficiency, and mild potential side effects. This review introduced the commonly used materials and various types of stimuli-responsive microneedles and the drug release mechanisms. In addition, this paper expounded the biomedical applications of stimuli-responsive microneedles as drug delivery systems in response to different stimuli and discusses the challenges and potential solutions for stimuli-responsive microneedles.
Needles ; Drug Delivery Systems/instrumentation* ; Microinjections/instrumentation* ; Humans ; Administration, Cutaneous

Objective:To investigate the correlation between the prognosis of late-onset depression(LOD)in the elderly and lncRNA expression levels and coping styles.Methods:Differential expression of lncRNAs in peripheral blood of LOD 92 patients was detected by a real-time quantitative PCR(qPCR)detection system, and the Hamilton Depression Scale(HAMD)and the Trait Coping Style Questionnaire(TCSQ)were used for psychological assessment.Results:Compared with the control group, the expression levels of TCONS_00019174(7.55 vs.4.36), ENST00000566208(6.48 vs.3.26), ENST00000517573(8.33 vs.5.32)and NONHSAT142707(6.78 vs.3.26)in elderly patients of the LOD group were significantly down-regulated( Z=5.09, 5.87, 4.35, 6.44, P<0.05); Compared with the low-expression subgroup, scores of anxiety/somatization[(3.83±1.40) vs.(6.39±2.35)], diurnal variation[(0.22±0.42) vs.(0.83±0.94)], retardation[(5.74±0.96) vs.(6.48±1.28)], hopelessness[(2.78±0.67) vs.(4.52±1.56)]and HAMD[(20.39±1.75) vs.(26.83±4.88)]in the high-expression subgroup were significantly lower( t=-4.50, -2.84, -2.22, -4.90, -5.96, P<0.05). The ΔCT value of TCONS_00019174 was negatively correlated with the reduction rates of anxiety/somatization, diurnal variation, retardation, sleep disturbance, hopelessness and HAMD( r=-0.40-0.66, P<0.05). The ΔCT value of ENST00000566208 was negatively correlated with the reduction rates of anxiety/somatization, sleep disturbance, hopelessness and HAMD( r=-0.47-0.62, P<0.01). The ΔCT values of ENST00000517573, NONHSAT034045 and NONHSAT142707 were negatively correlated with the reduction rates of retardation, sleep disturbance, hopelessness and HAMD( r=-0.39-0.76, P<0.05). The positive coping style was positively correlated with the reduction rates of HAMD, anxiety/somatization, retardation, sleep disturbance and hopelessness( r=0.38-0.55), while the negative coping style was negatively correlated with the reduction rates of HAMD, anxiety/somatization, sleep disturbance and hopelessness( r=-0.39-0.67, P<0.05). When TCONS_00019174, ENST00000566208, NONHSAT034045, NONHSAT142707, positive coping and negative coping were taken into the regression equation as variables for HAMD reduction, it was found that they were able to explain 32.4% of the variance for the reduction rate of the total HAMD score( t=-8.713, -3.584, -3.864, -2.257, 5.675, -2.357, P<0.05). Conclusions:TCONS_00019174, ENST00000566208, NONHSAT034045, NONHSAT142707, positive coping style and negative coping style are predictors of the prognosis of LOD in the elderly.

Objective:To analyze the clinical characteristics and predictive factors of SSc associated heart disease.Methods:The clinical data of patients with SSc from January 2016 to December 2021 in Ningbo Medical Center Lihuili Hospital were collected. Aight healthy controls come from the medicial examination center. They were divided into a positive group and a negative group based on whether heart involvement was present or not. The clinical manifestations of the two groups were compared by t test, Wilcoxon signed rank test and χ2 test and Logistic regression or ROC curve was used to analyze the prognostic risk of SSc associated heart disease. Then the transcriptome sequencing was used to analyze the differential gene expression. Results:①A total of 75 SSc patients were treated in our hospital, of which 6 patients with overlap syndrome and 1 patient with congenital heart disease were excluded. The clinical data of 68 patients were analyzed including 16 patients in the positive group and 52 patients in the negative group. Among the 16 patients with cardiac involvement, 12 patients (75.0%) had abnormal electrocardiogram, 9 patients (56.2%) with heart valve disease, 8 patients (50.0%) with abnormal cardiac structure and 8 patients (50.0%) with pericardial effusion. The biomarkers were elevated in 10 cases (83.3%). ②Univariate analysis showed that the positive group had a longer course of disease [120(11.2, 132) months vs 48(24, 90)months, Z=-2.08, P=0.037], and the rate of pulmonary arterial hypertension (50.0% vs 11.5%, χ2=11.07, P<0.001) and renal insufficiency(50.0% vs 3.8%, χ2=20.78, P<0.001) in the positive group were significantly higher than those in the negative group. Further Logistic regression analysis revealed that long course of disease [ OR (95% CI) =1.011 (1.001, 1.021), P=0.031], pulmonary arterial hypertension [ OR (95% CI) =5.431, 95% CI (1.065, 27.710), P=0.042] and renal insufficiency [ OR (95% CI) =30.444 (4.139, 223.938), P<0.001] were risk factors for SSc associated heart disease. ③Nail-fold videocapillaroscopy (NVC) was checked in 63 patients. The difference of abnormal NVC changes between the two groups was statistically significant (93.3% vs 58.3%, χ2=5.87, P=0.013). The total number of capillaries in the positive group was significantly less than that in the negative group [3.5(2, 4.8) vs 6 (5, 7), Z=-2.97, P=0.003]. Further ROC curve analysis showed that the total number of capillaries less than 4.5 predicted the occurrence of cardiac involvement (sensitivity was 80.0%, specificity was 83.8%), and the area under the ROC curve (95% CI) was 0.805 (0.061, 1.000, P=0.003).④The transcriptome of a total of 11 SSc patients (including 6 in the positive group and 5 in the negative group) and 8 healthy controls were analyzed to obtain the synchronously down regulated gene TNFRSF13B. The differences between the three groups were statistically significant ( χ2=11.88, P=0.003), especially in the positive group and the healthy controls( χ2=11.19, P=0.004). Conclusion:SSc patients with long course of disease accompanied by PAH and renal insufficiency are prone to have heart involvement. Early capillary endoscopy is also helpful to predict the risk of heart involvement. Moreover, TNFRSF13B genetic testing is helpful but further study is needed.