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.

ObjectiveTo investigate the role of DEAD-box helicase 3 X-linked （DDX3X） in immune-mediated liver injury （ILI）， and to clarify its mechanism by regulating endoplasmic reticulum stress （ERS）-dependent apoptotic pathway and its association with the clinical progression of hepatitis B. MethodsMice were given injection of concanavalin A （ConA） via the caudal vein to establish a model of ILI， PBS （control group） and different concentrations of ConA were injected into the tail vein of hepatocyte-specific DDX3X-knockout mice （DDX3X^ΔHep and DDX3X-flox mice （DDX3X^fl/fl）， respectively.. The log-rank survival analysis， measurement of the serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）， and HE staining of liver tissue were performed to assess liver injury， and qRT-PCR and Western Blot were used to measure the mRNA and protein expression levels of glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， and DDX3X in liver tissue. Intraperitoneal injection of 4-phenylbutyric acid （4-PBA， 100 mg/kg） was performed to inhibit ERS. Serum samples （n=30） and liver tissue samples （n=6） were collected from healthy controls， chronic hepatitis B （CHB） patients， and hepatitis B virus-associated liver failure （HBV-LF） patients； ELISA was used to measure the serum level of DDX3X， and qRT-PCR/Western Blot was used to analyze the expression of targets in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group of mice， the expression of DDX3X in the liver of mice induced by ConA was significantly increased after liver injury （P<0.05）， and hepatocyte-specific DDX3X knockout increased the 72-hour survival rate of mice by 55% （compared with 20% in the DDX3X^fl/fl group）， with significant reductions in the serum levels of ALT and AST （P<0.000 1） and the expression levels of the ERS markers GRP78 and CHOP （P<0.05）. After ERS was inhibited by 4-PBA， there was alleviation of liver injury （with reductions in ALT and AST， P <0.001） and a reduction in DDX3X expression （P<0.01）. The analysis of clinical samples showed that the mRNA and protein expression levels of liver DDX3X in CHB patients and HBV-LF patients were significantly higher than those in healthy controls （all P<0.01）， and there was a significant increase in the serum level of DDX3X in HBV-LF patients （P<0.000 1）. ConclusionDDX3X exacerbates ILI by regulating the ERS-dependent apoptotic pathway （GRP78/CHOP）， and its expression is associated with the progression of hepatitis B. Therefore， it can be used as a potential therapeutic target.

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.

Dental caries is a major disease that seriously endangers human oral health. Dental plaque biofilm composed of many microorganisms is the primary factor of dental caries. Inhibiting biofilm formation has become the focus of research on the prevention and treatment of dental caries. Streptococcus mutans and Candida albicans, as common pathogenic bacteria in the oral cavity, are closely related to the occurrence of dental caries. The interaction between the two can lead to the rapid onset of dental caries. In recent years, many studies have found that Candida albicans promotes the occurrence of caries by interacting with Streptococcus mutans, including physical adhesion, promoting the production of exopolysaccharides (EPS), reducing the pH of the microecological environment, forming a highly cariogenic acidic environment, and secreting quorum sensing molecules to trigger quorum sensing. As a communication mechanism between microorganisms, the quorum sensing system mainly includes three main types: autoinducing peptide (AIP) system, autoinducer-2 (AI-2) system, and Acyl-homoserine lactone (AHL) system. At present, quorum sensing has been shown to promote the occurrence of diseases by activating the expression of microbial pathogenicity-related genes, promoting EPS synthesis and biofilm formation. The CSP-ComDE and ComRS quorum sensing systems of Streptococcus mutans allow the bacteria to survive and cause disease in extreme environments that are unfavorable for survival, while the quorum sensing system of Candida albicans is mainly mediated by farnesol, which has a negative regulatory effect on the yeast-hyphae transformation of Candida albicans. Studying the quorum sensing phenomenon of the two bacteria is helpful to understand the etiology of caries. In recent years, many studies have reported the use of quorum sensing inhibitors in anti-microbial applications. The study of microbial quorum sensing systems and inhibitors will help the prevention and treatment of caries. With the increasing interest in biofilm-related research, and a new method for in-depth study of the biofilm formation process and quorum sensing behavior using microfluidic and chip laboratory technology is proposed. The author summarizes the cariogenic effects, the quorum sensing system and quorum sensing inhibitors of Streptococcus mutans and Candida albicans.

Objective:To compare the anticoagulant efficacy and safety between argatroban and heparin in patients with liver failure complicated with hepatic encephalopathy undergoing artificial liver treatment.Methods:A total of 207 patients with liver failure complicated with hepatic encephalopathy who received artificial liver treatment in the intensive care unit (ICU) of Wuxi No.5 People′s Hospital from January 2021 to October 2024 were enrolled, including 105 cases in the argatroban group and 102 cases in the heparin group. Changes in coagulation function, hemoglobin (Hb), platelet (PLT) count, and model for end-stage liver disease (MELD) score before and after artificial liver treatment were compared between the two groups. The formation of deep vein thrombosis in the lower extremities, coagulation in the extracorporeal circulation circuit and plasma separator, bleeding at the deep venous catheter site were compared between the two groups. The 28-day survival outcome of the patient were recorded. Two independent sample t-test, rank sum test, and chi-square test were used for statistical comparisons, and the Kaplan-Meier method and log-rank test were used to analyze the survival rate of patients. Results:There were no statistically significant differences in activated partial thromboplastin (APTT), international normalized ratio (INR), Hb and PLT count before and after artificial liver treatment in the argatroban group ( Z=-1.74, -1.80, -1.26 and -0.52, respectively, all P>0.05), while the MELD score after treatment was lower than that before treatment and the difference was statistically significant ( t=6.49, P<0.001). After artificial liver treatment, the APTT in the argatroban group was 47.10(42.65, 51.90) s, which was shorter than that in the heparin group (56.05(50.02, 63.00) s). The INR, Hb, and PLT count in the argatroban group were 2.00(1.65, 2.54), 98.00(88.00, 112.00) g/L, and 92.00(75.50, 106.00)×10 9/L, respectively, which were all higher than those in the heparin group, which were 1.56(1.22, 1.93) g/L, 90.50(80.00, 104.75) g/L, and 74.00(64.75, 99.50)×10 9/L, respectively. The differences were all statistically significant ( Z=-7.16, -5.28, -3.05 and -3.32, respectively, all P<0.05). There was no statistically significant difference in MELD scores between the two groups ( P=0.250). The incidence of coagulation in the extracorporeal circulation circuit and plasma separator and bleeding at the deep venous catheter site in the argatroban group was 5.71%(6/105) and 1.90%(2/105), respectively, which were both lower than those in the heparin group (14.71%(15/102) and 9.80%(10/102), respectively). The differences were both statistically significant ( χ2=4.59 and 5.91, respectively, both P<0.05). At the end of the 28-day follow-up, the mortality rates in the argatroban group and the heparin group were 22.9%(24/105) and 34.3%(35/102), respectively, and the difference was not statistically significant ( χ2=3.33, P=0.068). There was no statistically significant difference in the 28-day survival rate between the argatroban group and the heparin group ( χ2=2.09, P>0.05). Conclusions:Argatroban has a relatively minor impact on PLT count and Hb when it is used in artificial liver treatment for patients with liver failure complicated with hepatic encephalopathy. The incidence of coagulation in extracorporeal circulation circuits and plasma separators is low, and the risk of bleeding at the deep venous catheters is low. Argatroban is highly safe, which provides a new anticoagulation option for patients with a high risk of bleeding.

Objective To analyze the application characteristics,trends,and special advantages of anti-infection research using the Bayesian method,and to provide methodological reference for the development of anti-infection research.Methods PubMed,CNKI and WanFang Data were electronically searched for the studies on anti-infection using Bayesian method published from January 1,2015 to November 21,2023.The relevant information of publication time,anti-infection type,sample size,Bayesian characteristics and Bayesian application pattern were analyzed descriptively and reviewed.Results A total of 86 studies were included,of which 41.9％were observational studies,only 7.0％were enterprise-initiated studies,and 48.8％were mentioning prior information studies.There was no domestic intervention study.The application characteristics and advantages of Bayesian method in intervention study,observational study and pharmacokinetic study are different.In intervention researches and observational researches,the application of Bayesian design decision and the application of Bayesian analysis and estimation accounts for 69.2％and 52.8％at most,respectively.Conclusions The Bayesian method is flexible,can be used for small sample sizes and complex model research,and can deal with uncertainty.In intervention studies in the field of anti-infection in China,the Bayesian method has not been applied widely.Only a handful of studies applying Bayesian method have been initiated by companies.In the future,it is still necessary to promote the advantages and application scenarios of Bayesian methods in the field of anti-infection research and strengthen the standardization of the application of Bayesian method.

Objective To compare the effects of non-invasive intermittent oxygen-driven nebulization,non-invasive intermittent air-driven nebulization,and non-invasive simultaneous air-driven nebulization on the dynamic changes of partial pressure of carbon dioxide(PtCO2),pulse oxygen saturation(SpO2),and heart rate during nebulization,as well as the therapeutic effects in patients with acute exacerbation of chronic obstructive pulmonary disease(COPD).Methods A total of 99 patients with acute exacerbation of COPD requiring non-invasive mechanical ventilation and nebulization were randomly divided into a control group,an experimental group one,and an experimental group two,with 33 patients in each group.The control group was given non-invasive intermittent oxygen-driven nebulization,the experimental group one was given non-invasive intermittent air-driven nebulization,and the experimental group two was given non-invasive simultaneous air-driven nebulization.The changes in PtCO2,SpO2,and heart rate at 0 min,5 min,10 min,15 min during nebulization,5 min,10 min,and 15 min after nebulization were recorded.The values of arterial blood gas PaCO2 and PaO2 were recorded every morning from before treatment to the 7th day of treatment.The length of hospital stay in the three groups was also recorded.Results The comparison of PtCO2 during nebulization among the three groups showed that there were statistically significant differences in the main effect of time and the interaction effect of time and group(P<0.001).The PtCO2 values in the control group showed a linear relationship with time(F=10.166,P=0.003),increasing over time;the PtCO2 values in the experimental group one showed a linear relationship with time(F=10.544,P=0.003),decreasing over time;the PtCO2 values in the experimental group two showed a linear rela-tionship with time(F=20.003,P<0.001),decreasing over time.A one-way ANOVA was conducted on the PtCO2 values at each time point in the three groups.The PtCO2 value at 15 min of nebulization in the control group was higher than that in the experimental group one and the experimental group two.There were statistically signifi-cant differences in the difference in PtCO2 before and after nebulization(dPtCO2)between the experimental group one and the experimental group two and the control group(P<0.05).A one-way ANOVA was conducted on the PtCO2 values at each time point during the observation period after nebulization.The results showed that there were statistically significant differences in PtCO2 at 0 min and 5 min after nebulization among the three groups(P<0.05),while there were no statistically significant differences in PtCO2 at 10 min and 15 min after nebulization among the three groups(P>0.05).The comparison of SPO2 during nebulization among the three groups showed that there were statistically significant differences in the interaction effect of time and group(P<0.05).The SPO2 values in the experimental group one decreased over time.The SPO2 values at 10 min and 15 min of nebulization in the control group were higher than those in the experimental group one and the experimental group two.All three groups could improve PaCO2 in arterial blood gas with the treatment days(P<0.05).Conclusions All three nebu-lization treatment methods can achieve good therapeutic effects.However,non-invasive intermittent oxygen-driven nebulization can increase PtCO2 and SPO2 during nebulization;non-invasive intermittent air-driven nebulization can decrease PtCO2 and SPO2 during nebulization;non-invasive simultaneous air-driven nebulization can decrease PtCO2 and maintain stable SPO2 during nebulization.Therefore,non-invasive simultaneous air-driven nebulization is a relatively safer nebulization inhalation method and is worthy of clinical promotion.

Objective To investigate the proportions of myeloid-derived suppressor cells(MDSCs)and their subsets,including poly-morphonuclear MDSCs(PMN-MDSCs),early-stage MDSCs(e-MDSCs),monocytic MDSCs(M-MDSCs),and lectin-like oxidized low-density lipoprotein receptor-1(LOX-1)positive PMN-MDSCs,in the peripheral blood of ovarian cancer(OC)patients and ana-lyze their correlations with clinicopathological parameters of the patients.Methods The proportions of MDSCs and their subsets in the peripheral blood of 38 OC patients(OC group)and 46 healthy individuals(healthy control group)were detected by flow cytometry.The levels of serum IL-10 and TGF-β were detected using ELISA.The OC group was further divided into LOX-1 high and low expres-sion subgroups based on the median proportion of LOX-1+PMN-MDSCs in MDSCs.Results The proportions of MDSCs,PMN-MDSCs,and LOX-1+PMN-MDSCs in the peripheral blood mononuclear cells(PBMCs)of the OC group were significantly higher than those in the healthy control group(U=492,P＜0.001;t=8.741,P＜0.000 1;U=223,P＜0.000 1).The proportions of M-MDSCs and e-MDSCs in the OC group were significantly lower than those in the healthy control group(t=4.366,P＜0.000 1;t=6.927,P＜0.000 1).The proportion of LOX-1+PMN-MDSCs in the lymph node metastasis group of OC patients was significantly higher than that in the non-metastasis group(t=2.249,P＜0.05).The levels of serum IL-10 and TGF-β in the OC group were significantly higher than those in the healthy control group(P＜0.05).In addition,the level of serum TGF-β in the LOX-1 high expression group was significantly higher than that in the LOX-1 low expression group(t=2.302,P＜0.05).Conclusion The proportion of LOX-1+PMN-MDSCs in the peripheral blood of OC patients is significantly increased and closely related to lymph node metastasis.

Objective To provide ideas and reference for the anti-infective drug treatment and pharmaceutical care of brain abscess caused by Nocardia brasiliensis.Methods Clinical pharmacists participated in the treatment of a patient with brain abscess caused by Nocardia brasiliensis.According to the patient's medical history,clinical symptoms,and test results,clinical pharmacists refer to the guidelines assisted physician to formulate the anti-infection treatment scheme of trimethoprim-sulfamethoxazole(SMZ-TMP)combined with imipenem/cilastatin and amikacin,and the pharmaceutical care.The dosage of amikacin was adjusted through therapeutic drug monitoring(TDM),and promptly identified adverse reactions such as myelosuppression caused by linezolid and SMZ-TMP.Results The physician adopted the pharmacist's suggestion,and the patient was discharged after treatment.Conclusion The anti-infection regimen for brain abscess caused by Nocardia brasiliensis depends on the drug sensitivity data of Nocardia,the severity of infection,the immune state of the host,and the PK/PD characteristics and adverse reactions of antibiotics.By participating in the pharmaceutical care of brain abscess caused by Nocardia brasiliensis,clinical pharmacists assisted physicians in optimizing drug treatment plans,ensuring the safety and effectiveness of clinical medication.