ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley （SD） rats were randomly divided into a normal group， model group （M）， Sini San group （MS， 2.5 g·kg^-1）， and fluoxetine group （MF， 2 mg·kg^-1）. Except for the normal group， rats in the other three groups were subjected to chronic unpredictable mild stress （CUMS）. After 8 weeks， the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum corticosterone （CORT）， adrenocorticotropic hormone （ACTH）， corticotropin-releasing factor （CRF）， lipopolysaccharide （LPS）， Zonulin， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， γ-aminobutyric acid （GABA） levels in the hippocampus and prefrontal cortex， and brain-derived neurotrophic factor （BDNF） levels in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy， and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group， the sucrose preference of rats in the model group was significantly reduced （P0.01）， whereas it was significantly increased in the Sini San group compared with the model group （P0.05）. Compared with the normal group， hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased （P0.05）， and compared with the model group， both were significantly increased in the Sini San group （P0.05， P0.01）. Compared with the normal group， serum LPS and Zonulin levels in the model group were significantly increased （P0.05， P0.01）， and compared with the model group， Zonulin levels in the Sini San group were significantly decreased （P0.05）. No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group， widened and blurred tight junctions， sparse and shortened microvilli， and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group， which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators， liver function， and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.

ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley （SD） rats were randomly divided into a normal group， model group （M）， Sini San group （MS， 2.5 g·kg^-1）， and fluoxetine group （MF， 2 mg·kg^-1）. Except for the normal group， rats in the other three groups were subjected to chronic unpredictable mild stress （CUMS）. After 8 weeks， the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum corticosterone （CORT）， adrenocorticotropic hormone （ACTH）， corticotropin-releasing factor （CRF）， lipopolysaccharide （LPS）， Zonulin， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， γ-aminobutyric acid （GABA） levels in the hippocampus and prefrontal cortex， and brain-derived neurotrophic factor （BDNF） levels in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy， and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group， the sucrose preference of rats in the model group was significantly reduced （P<0.01）， whereas it was significantly increased in the Sini San group compared with the model group （P<0.05）. Compared with the normal group， hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased （P<0.05）， and compared with the model group， both were significantly increased in the Sini San group （P<0.05， P<0.01）. Compared with the normal group， serum LPS and Zonulin levels in the model group were significantly increased （P<0.05， P<0.01）， and compared with the model group， Zonulin levels in the Sini San group were significantly decreased （P<0.05）. No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group， widened and blurred tight junctions， sparse and shortened microvilli， and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group， which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators， liver function， and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.

Objective: To evaluate the intervention efficacy of integrated group social skills training on social ability in school age patients with high functioning ASD, so as to provide a reference for improving social skills in children with high functioning ASD. Methods: From January 2021 to December 2023, 62 children aged 7-12 with high functioning ASD who visited the Children s Psychiatry Outpatient Department of the Affiliated Kangning Hospital of Ningbo University were recruited, and were randomly divided into a training ( n =31) and a control group ( n =31) by a random number table method. The training group received a 20 week structured group social training program (mental interpretation courses and social courses), while the control group received only conventional treatment. Chinese version of Griffith Empathy Measure Parent Ratings (GEM-PR) and Social Response Scale (SRS) were used to assess the symptoms of social deficits before and after treatment. Emotional face recognition tasks and eye movement trajectories were used to test the characteristics of social visual attention in children with ASD. Group comparison was conducted using t-test and Mann-Whitney U test. Results: At baseline, there were no significant differences in GEM-PR score ( t = -1.20 to -0.81), SRS score ( t =-0.36-1.75), emotional face recognition accuracy and reaction time ( t =-0.58-1.85), and eye movement trajectory ( U/t =-1.63-0.29) between the two group ( P >0.05). After intervention, the total GEM-PR score and empathic cognitive factor score of training group [18.00(10.00，24.00)，9.00(8.00，13.00)] were significantly higher than those of the control group [12.00(-1.00，18.00)，2.00(-2.00，7.00)], and the total SRS score and social cognition, social perception, social communication, social motivation (73.23±14.20, 16.16±2.72, 6.58±2.50, 24.29±5.61, 9.52±3.73) were significantly lower than those of the control group (95.26±15.29, 19.90±2.84, 12.58±2.49,31.94±6.38, 13.74±4.81) ( U/t =-2.38, -4.59; -5.88, -5.29, -9.47, -5.01, -3.87, P <0.05). The overall correct rate of emotional face recognition and the correct rate of angry, fearful and neutral faces recognition in the training group [(81.55±6.62)%，(76.86±12.06)%，(79.61±12.42)%，(94.27±6.26)%] were significantly higher than the control group [(70.55±13.82)%，(62.82±18.77)%，(67.18±18.85)%，(79.60±20.05)%], and the average reaction time [(2 226.70±274.43)ms] was lower than the control group [(2 417.27±324.10)ms] (t=4.00, 3.50, 3.07, 3.89, -2.42, P<0.05). The time to first eye gaze [764.74 (748.64, 793.73) ms] in the training group was significantly lower than that in the control group [810.92 (782.86, 877.42) ms], and the proportion of moderatetohigh intensity attention area in the face [(37.37±1.27)%] was significantly higher than that in the control group [(30.34±1.23)%] (U/t=3.44, 8.89, P<0.05). Conclusion Integrated group social training can significantly improve the social communication and empathy ability of high functioning ASD children, increase active attention and recognition ability of faces, and improve mental development of children with ASD.

Myocardial ischemia-reperfusion injury （MIRI） is a common cardiac pathological process， resulting from the combined effects of multiple mechanisms involving metabolic changes and mitochondrial dysfunction. Mitochondrial quality control （MQC）， as a key regulatory mechanism， may serve as an important target for the prevention and treatment of MIRI. In recent years， traditional Chinese medicine （TCM） has demonstrated unique advantages in the field of improving MIRI， with multiple targets， multiple pathways， and low toxic and side effects. It has gained widespread clinical recognition and application. Through systematically organizing and summarizing recent studies on the targeting of MQC by monomers， active fractions， herb pairs， compound formulas and related preparations of TCM to improve MIRI， this paper finds that monomers and active fractions of TCM （such as schisandrin B， isoliquiritigenin， calenduloside E， berberine， Lycium barbarum polysaccharides and so on） as well as TCM herb pairs， compound formulas， and related preparations （couplet medicinals of Fuzi-Ganjiang， Yixin formula， Shuangshen ningxin capsule， Baijin formula， Yiqi huoxue decoction and so on）， can alleviate MIRI by activating MQC to reduce oxidative stress-induced damage， promote mitochondrial biogenesis， maintain mitochondrial fission/fusion homeostasis， regulate mitochondrial autophagy， and restore mitochondrial calcium homeostasis.

Objective: To explore the application effect of a guided self help intervention based on dialectical behavior therapy (DBT) to address non suicidal self injury (NSSI) behavior among college students, so as to provide a reference for reducing the occurrence of NSSI behavior in this population. Methods: A total of 106 college students with NSSI admitted to the Department of Child and Adolescent Psychology, the Second Affiliated Hospital of Jining Medical University from January 2021 to January 2023 were selected and divided into an observation group and a control group, with 53 cases in each group, using a random number table method. The control group received routine medication treatment and psychological intervention, while the observation group, on the basis of the interventions provided to the control group, implemented dialectical behavior therapy based guided self help. The approach combines group activities, individual counseling, and selfdirected learning, covering four core modules: mindfulness training, distress tolerance, interpersonal effectiveness, and emotion regulation. Meanwhile, data collection, skill check ins, and personalized recommendation pushes were conducted through a WeChat. Both groups were intervented for 12 weeks. Before the intervention and after the intervention, the Adolescent Non suicidal Self injury Behavior Questionnaire, Ottawa Self injury Inventory (OSI), and Barratt Impulsiveness Scale (BIS) were used to evaluate the patients, and the levels of serum neurotransmitters were detected. The χ 2 test, t test, and Cochran s Q test were used for data comparison and analysis. Results: The incidence rates of NSSI in the observation group after 3, 6, and 12 weeks of intervention were 47.17%, 16.98%, and 5.66%, respectively, all lower than those in the control group (67.92%, 35.85%, 20.75%) ( χ 2=4.67, 4.85, 5.27,all P <0.05). After 12 weeks of intervention, in the NSSI Behavior Questionnaire, the total score of the observation group was (17.94±2.69) points, which was lower than that of the control group (23.04±5.11) points; in the Function Questionnaire, the total score of the observation group was (53.24±8.94) points, which was higher than that of the control group (47.74±8.00) points（both P ＜0.05）. In terms of the OSI, the total score of the observation group was (4.49±0.62) points, lower than that of the control group (6.25±0.81) points;in the BIS, the total score of the observation group was (80.76±7.94) points, lower than that of the control group (87.74±9.34) points，and the differences between groups were statistically significant(both P<0.05). After the intervention, the level of 5-hydroxytryptamine in the observation group was (67.93±5.42) ng/mL, higher than (44.72±5.54) ng/mL of the control group; the levels of substance P and cortisol in the observation group were (35.82±4.47) ng/L and (75.64±8.02) μg/L, respectively, both lower than (48.14±5.32) ng/L and (94.53±10.78) μg/L of the control group, and the differences were statistically significant (all P <0.05). Conclusion The guided self help intervention based on DBT is helpful for reducing NSSI behavior among college students.

ObjectiveTo investigate growth hormone secretagogue receptor （GHSR） rs2922126 gene polymorphisms and their association with genetic susceptibility to nonalcoholic fatty liver disease （NAFLD） in the Chinese Han population in Qingdao， China， and to provide a basis for diagnosis and treatment. MethodsA total of 220 patients who were admitted to Qingdao Municipal Hospital from June 2022 to June 2023 and were diagnosed with NAFLD based on radiological examination were enrolled as NAFLD group， and 167 healthy individuals during the same period of time were enrolled as control group. Fasting blood samples were collected from all subjects， and related biochemical parameters were measured. Whole blood DNA was extracted， and polymerase chain reaction and MALDI-TOF mass spectrometer were used for genotyping. The chi-square test was used for comparison of categorical data between groups， and the independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between groups. The binary logistic regression analysis was used to investigate the risk of NAFLD. ResultsCompared with the control group， the NAFLD group had significantly higher age， body mass index （BMI）， fasting plasma glucose， triglyceride， gamma-glutamyl transpeptidase， alkaline phosphatase， alanine aminotransferase， and aspartate aminotransferase， as well as a significantly lower level of high-density lipoprotein （all P0.05）. The distribution of GHSR rs2922126 genotypes was consistent with the Hardy-Weinberg equilibrium， suggesting population representativeness in the subjects enrolled （NAFLD group： P=0.106； control group： P=0.849）. There was no significant difference in the distribution of AA， TA， and TT genotypes at GHSR rs2922126 locus between the control group and the NAFLD group （P=0.099）， and there was also no significant difference in allele frequency between the two groups （P=0.063）. In the recessive model of A allele， there was a significant difference in the distribution of AA homozygote and TA+TT genotype between the NAFLD group and the control group （P=0.032）. The binary logistic regression analysis showed that in the recessive model of A allele， AA homozygote carriers had an increased risk of NAFLD compared with TA+TT genotype carriers （odds ratio ［OR］=1.712， 95% confidence interval ［CI］： 1.045 — 2.807， P=0.033）. There was still a significant difference after adjustment for sex， age， and BMI （OR=2.156， 95%CI： 1.221 — 3.808， P=0.008）. In the NAFLD group， AA genotype carriers had a significantly higher serum level of total cholesterol （TC） than TT+TA carriers （Z=-1.99，P=0.046）. ConclusionGHSR rs2922126 AA genotype may be associated with the increased risk of NAFLD in the Chinese Han population in Qingdao， and GHSR rs2922126 AA genotype is associated with the increase in TC in NAFLD patients.

BACKGROUND: The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections. METHODS: This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups. RESULTS: A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups. CONCLUSION: The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs. REGISTRATION ClinicalTrials.gov , NCT05173493.
Humans ; Helicobacter Infections/drug therapy* ; Helicobacter pylori/pathogenicity* ; Male ; Female ; Prospective Studies ; Middle Aged ; Anti-Bacterial Agents/adverse effects* ; Adult ; Aged ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) "difficult-to-treat". Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances. Addressing lower strontium (Sr) levels in arthritic synovial microenvironment, we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells (SMSCs). Here, we developed an optimized system that boosts the yield of SMSC-derived exosomes (SMSC-EXOs) and improves their miRNA profiles with an elevated proportion of beneficial miRNAs, while reducing harmful ones by pretreating SMSCs with Sr. Compared to untreated SMSC-EXOs, Sr-pretreated SMSC-derived exosomes (Sr-SMSC-EXOs) demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA. Our results illustrate Alix's crucial role in Sr-triggered miRNA loading, identifying miR-143-3p as a key anti-TMJOA exosomal component. Interestingly, this system is specifically oriented towards synovium-derived stem cells. The insight into trace element-driven, site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.
MicroRNAs/metabolism* ; Mesenchymal Stem Cells/drug effects* ; Osteoarthritis/drug therapy* ; Exosomes/drug effects* ; Strontium/pharmacology* ; Synovial Membrane/cytology* ; Humans ; Animals ; Temporomandibular Joint Disorders/therapy* ; Temporomandibular Joint