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 This study aimed to investigate the regulatory effect of electroacupuncture(EA)intervention on the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxia-inducible factor 1α(HIF-1α)signaling pathway in the hippocampal tissue of Alzheimer's disease(AD)model mice and its effect on astrocytic glycolytic function,further exploring how EA ameliorates AD-related cognitive impairment.Methods Eighteen APP/PS1 mice were randomly divided into model,EA,and sham EA groups(n=6)using the random number table method.Six wild-type C57BL/6J mice served as the control group.The EA group received EA stimulation at acupoints"Shenshu"(BL23),"Baihui"(GV20),and"Zusanli"(ST36)(administered every other day,20 min per session,for 4 weeks).The sham EA group received identical needle insertions at the same acupoints without electrical stimulation.The control and model groups were only restrained.Cognitive function was assessed using the Morris water maze and Y-maze spontaneous alternation tests.Hippocampal morphology was observed via hematoxylin and eosin staining.Hippocampal β-amyloid peptide 1-42(Aβ1-42)deposition was detected using immunohistochemistry.HIF-1α protein expression,the p-Akt/Akt,and p-mTOR/mTOR ratios were measured using Western blotting.Pyruvate kinase M2(PKM2)and lactate dehydrogenase A(LDHA)activities were quantified using enzyme-linked immunosorbent assay.Hexokinase(HK)activity and L-lactate content were determined using a colorimetric assay.Co-localization of LDHA with the astrocyte marker glial fibrillary acidic protein was quantitatively analyzed using immunofluorescence double-labeling combined with Pearson's correlation coefficient.Results Compared with the control group,the model group mice exhibited cognitive decline,as shown by prolonged escape latency(P<0.01),reduced number of platform crossings,lower time spent in the target quadrant,and decreased spontaneous alternation accuracy(P<0.01).The hippocampal neurons showed cell body swelling,deeper nuclear staining,enlarged intercellular spaces,and increased average optical density of Aβ1-42(P<0.01).The p-Akt/Akt and p-mTOR/mTOR ratios,as well as HIF-1α protein expression,were elevated(P<0.01).PKM2,LDHA,HK,and L-lactic acid levels were significantly increased(P<0.01),and the co-localization coefficient of LDHA with astrocytes was enhanced.Compared to the model group,the EA group of mice showed improved cognitive function.The hippocampal neurons had more intact structures,with a more uniform cell distribution.The average optical density of Aβ1-42 decreased(P<0.01),and the p-Akt/Akt and p-mTOR/mTOR ratios,as well as HIF-1α protein expression,decreased(P<0.01).PKM2,LDHA,HK,and L-lactic acid levels decreased(P<0.05),and the co-localization coefficient of LDHA with astrocytes significantly decreased(P<0.01).No significant improvement was observed in any of the indicators in the sham EA group compared with the EA group.Conclusion EA at"Shenshu"(BL23),"Baihui"(GV20),and"Zusanli"(ST36)ameliorates cognitive dysfunction in AD model mice.The underlying mechanism may involve suppressing the overactivation of the hippocampal Akt/mTOR/HIF-1α signaling pathway,thereby downregulating key glycolytic enzyme activities and reducing abnormal lactate accumulation.Furthermore,the astrocytic glycolytic metabolic pathway may constitute a key therapeutic target for this intervention.

Objective:To investigate the effect of left colonic artery (LCA) preservation on rectal cancer patients' short-term postoperative anal function and quality of life.Methods:Two-hundred ninty-two patients with rectal cancer at the Department of Gastrointestinal Surgery of Peking University First Hospital between Jan 2022 and Dec 2023 were enrolled . The patients were divided into two groups according to whether the LCA was preserved during surgery or not. The LARS scale and EORTC QLQ-CR29 quality of life questionnaire were used to assess postoperative anal function and quality of life.Results:There were no significant differences between the two groups in terms of the amount of surgical blood loss and the number of lymph node dissections in the root No. 253 group and the time to postoperative voiding (all P>0.05). However, the LARS scores at 1 and 3 months postoperatively were significantly lower in the preserved LCA group than in the LCA nonpreserved group, especially for gas incontinence, loose stool leakage, and number of bowel movements (all P<0.05). The EORTC QLQ-CR29 scores showed that the LCA preserved group recovered significantly better than the non-preserved group in terms of postoperative voiding dysfunction ( P=0.007), urinary incontinence ( P=0.006), mucus discharge ( P=0.009), and fecal incontinence symptoms ( P<0.001). Male sexual dysfunction recovery was quicker in the preserved LCA group ( P=0.043), but there was no significant difference between the two groups at 3 months postoperatively( P>0.05). Conclusion:Preservation of the left colonic artery in low anterior resection of rectal cancer helps to reduce the incidence of postoperative low anterior resection syndrome, improve genitourinary symptoms, and improve patients' quality of life.

Objective:Analyze the risk factors of gastrointestinal perforation caused by foreign body and summarize the experience of surgical treatment of foreign bodies.Method:From Jan 2008 to Dec 2023, 89 patients with foreign bodies in the digestive tract were admitted to the Department of Gastrointestinal Surgery, Peking University First Hospital. Relevant data were collected and binary logistic regression was used to analyze the independent risk factors for intestinal perforation, resection and anastomosis of intestine or enterostomy/colostomy.Results:The mean age of 89 patients was (60.1±16.2) years old, 65 patients (73%) had unintentionally ingested foreign bodies. The most common foreign bodies were jujube pits (40 cases). Thirty-nine patients diagnosed with gastrointestinal perforation. Binary Logistic regression analysis showed that the total number of leukocytes ( OR=4.085, 95% CI: 1.214-13.745, P=0.023), sharp foreign body ( OR=26.124, 95% CI: 5.194-131.392, P<0.001), and the location of foreign body ( OR=3.980, 95% CI: 1.178-13.465, P=0.026) were the independent risk factors for gastrointestinal perforation. Thirty-three patients underwent gastrointestinal repair surgery, and 36 patients underwent resection and anastomosis of intestine or enterostomy/colostomy. Binary Logistic regression analysis showed that the foreign body located in the colorectum ( OR=71.928, 95% CI: 4.646-1 113.479, P=0.002) and the length of the foreign body ≤2.5 cm ( OR=5.791, 95% CI: 1.606-20.882, P=0.007) were the independent risk factors for resection and anastomosis of intestine or enterostomy/colostomy. Conclusions:Leukocyte count ≥10×10 9/L, sharp foreign body, and location of foreign body are independent risk factors for gastrointestinal perforation. Foreign body located in the colorectum and foreign body length ≤2.5 cm are risk factors for resection and anastomosis of intestine or enterostomy/colostomy.

Objective To analyze the efficacy of rTMS with different frequencies for PSD patients and analyze their EEG characteristics.Methods A total of 123 PSD patients admitted in our de-partment from May 2022 to May 2024 were recruited,and according to the frequency of rTMS,they were divided into high-frequency group(41 cases),intermediate-frequency group(41 cases)and low-frequency group(41 cases).Video fluoroscopic swallowing study(VFSS)was used to evaluate the swallowing function of patients swallowing different foods in the frontal and lateral positions.The swallowing function,motor evoked potential(MEP)of mandibular hyoid muscle,EEG characteristics and adverse reactions were compared among the groups.Results Compared with the high-frequency group,the VFSS score and MEP amplitude were decreased remarkably,while the Wadian drinking water test score and MEP latency were increased notably in the middle-frequency group and the low-frequency group(P＜0.05).The low-frequency group had signifi-cantly lower VFSS score and MEP amplitude(6.02±1.12 vs 6.57±1.01,102.25±19.81 μV vs 131.84±18.61 μV,P＜0.05),and higher Wadian drinking water test score and extended MEP latency than the intermediate-frequency group(2.03±0.31 vs 1.65±0.32,11.15±1.28 ms vs 9.21±1.36 ms,P＜0.05).After intervention,the amplitudes of the left anterior temporal lobe,the left middle temporal lobe,the middle central lobe,the left upper lobe and the right occipital lobe were gradually decreased in the high-frequency group,the middle-frequency group and the low-frequency group in order,with statistical significances(P＜0.05).Conclusion High-frequency rTMS can effectively regulate the MEP of mandibular hyoid muscle and EEG characteristics in PSD patients,improve swallowing function,and have no obvious adverse reactions,with high safety.

Acute pancreatitis(AP)is a frequently encountered acute abdominal syndrome in clinical settings,and the integrated model of traditional Chinese and Western medicine(TCM-WM)has demonstrated notable advantages in the diagnosis and treatment of AP.To systematize and standardize clinical practices related to develop clinical pathway for integrated TCM-WM diagnosis and treatment of AP,which enhances the efficiency and quality of patient care.This pathway focuses on AP,a common acute and life-threatening disease within the digestive system,and outlines that the central pathological mechanism involves pancreatic injury and localized inflammation resulting from the abnormal activation of pancreatic enzymes.It has the characteristics of rapid onset,multiple causes,and complex manifestations.Severe cases can be life-threatening.At present,conventional treatments encompass a diverse range of modalities.Moreover,traditional Chinese medicine(TCM)holds distinct advantages in alleviating relevant symptoms,and TCM-WM is gaining increasing prevalence.To enhance the standardization and consistency of diagnostic and therapeutic practices,this clinical pathway clearly delineates the target patient population,which includes individuals diagnosed with abdominal pain disorder according to TCM and with AP in accordance with WM criteria,as well as the corresponding inclusion standards.The diagnostic framework integrates both TCM and WM guidelines,and further incorporates disease staging,severity grading,and syndrome differentiation to support a comprehensive and integrated diagnostic strategy.The treatment integrates approaches from both TCM and WM.Within the WM framework,interventions consist of basic supportive care,infection control,nutritional support,and the management of complications.In the context of TCM,the protocol includes syndrome differentiation and corresponding therapeutic strategies(Distinct syndrome patterns are identified and managed during the acute and convalescent phases),such as acupuncture and retention enema.This clinical pathway addresses multiple key components,including preventive strategies,post-treatment follow-up,criteria for evaluating therapeutic efficacy,admission and discharge,admission examination protocols,discharge criteria,and the rationale for deviations or withdrawal from the pathway.It is designed to provide a systematic and standardized reference framework for relevant clinical practices.

Objective:To assess the effects of allergens on interleukin-18 (IL-18), IL-18 binding protein a (IL-18BPa), and IL-18 receptor α (IL-18Rα) expression levels in different monocyte subtypes of the peripheral blood samples of allergic asthma (AA) patients, and the correlations between the percentage of IL-18 +classical monocytes and plasma levels of pro-inflammatory cytokines. Methods:A cross-sectional study. Blood samples were collected from 28 healthy controls and 33 patients experiencing acute attack of AA based on a positive skin prick test of Henan Provincial People′s Hospital from February 2023 to April 2024. Flow cytometry was used to assess the effects of allergens on IL-18, IL-18BPa, and IL-18Rα expression levels in the classical, intermediate, and non-classical monocytes of the peripheral blood samples of AA patients. Kruskal-Wallis test and Pairwise test were used to analyze statistical significance between groups. Plasma tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) levels were estimated using Bioplex assays. Pearson correlation test was used to determine the association between the percentage of IL-18 +classical monocytes and the plasma levels of IL-1β and TNF-α. Results:Compared with healthy controls, the percentages of classical and non-classical monocytes in the peripheral blood of AA patients were reduced by 20.2% ( Z=-3.89, P<0.001) and 45.8% ( Z=-4.01, P<0.001), respectively. Allergens increased the percentages of classical, intermediate, and non-classical monocytes in AA patients in vitro by 13.1%-61.5% (all P<0.05). Compared with healthy controls, the percentages of IL-18 expression in classical monocytes of AA patients was elevated by 1.08-fold ( Z=-6.40, P<0.001), whereas the percentages of IL-18 expression in intermediate and non-classical monocytes were reduced by 52.7% ( Z=-6.40, P<0.001) and 3.23% ( Z=-3.13, P=0.001), respectively. Allergens upregulated IL-18 expression by 16.4%-67.8% in the classical and intermediate monocytes of AA patients (all P<0.05). Compared with healthy controls, IL-18BPa expression level was lower in the three monocyte subtypes of AA patients (all P<0.05). However, allergens upregulated IL-18BPa expression by 8.9% and 13.3% in the classical monocytes (both P<0.05). Compared with healthy controls, IL-18Rα expression was elevated by 1.29-fold in the classical monocytes of AA patients ( Z=-6.40, P<0.001). Allergens upregulated IL-18Rα expression by 17.6%-39.2% in the three monocyte subtypes of AA patients (all P<0.05). Plasma levels of IL-1β and TNF-α in the AA patients were increased compared to those in healthy controls (all P<0.001), and correlated with the percentage of IL-18 +classical monocytes ( r=0.451, 0.714; both P<0.05). Conclusions:Allergens may participate in the inflammatory response of AA by inducing the differentiation of monocytes and the expression levels of IL-18, IL-18BPa and IL-18Rα in different blood monocytes subtypes. Classical monocytes are the potential source of elevated plasma IL-18 level in AA patients.

Objective:To evaluate the changes in left ventricular structure and function in pregnant women with different severities of hypertensive disorders of pregnancy（HDP）using conventional echocardiographic parameters，strain，and tissue-tracking mitral annulus displacement（TMAD）parameters，and to validate and compare the application value of strain and TMAD parameters.Methods:A total of 148 singleton pregnant women with HDP and 100 healthy pregnant women（HP group）who attended the Third Affiliated Hospital of Zhengzhou University from October 2023 to July 2024 were selected. Conventional echocardiographic parameters，strain，and TMAD parameters were collected. Based on the severity of the disease，HDP patients were divided into the gestational hypertension group（GH group， n=49），non-severe preeclampsia group（NSPE group， n=35），and severe preeclampsia group（SPE group， n=64）. The differences in various parameters between the HP，GH，NSPE，and SPE groups were compared. The correlation between the displacement ratio of the midpoint of the mitral valve annulus in the apical 4-chamber（AP4 Midpt%），the displacement ratio of the midpoint of the mitral valve annulus in the apical 2-chamber（AP2 Midpt%）and left ventricular global longitudinal strain（LVGLS）were analyzed，and ROC curves were plotted to analyze and compare the diagnostic efficacies of LVGLS，AP4 Midpt% and AP2 Midpt% for left ventricular function changes in HDP pregnant women. Results:① The analysis revealed no statistically significant differences in maternal age and height between the HP group and the HDP subgroups（all P>0.05）. In contrast，statistically significant differences were observed in gestational age，systolic blood pressure，diastolic blood pressure，body mass index，and body surface area（all P<0.05）. Additionally，significant differences were noted in left ventricular mass，left ventricular interventricular septum thickness at end-diastole，left ventricular posterior wall thickness at end-diastole，left ventricular end-diastolic dimension，left ventricular end-systolic dimension，left ventricular end-diastolic volume，left ventricular end-systolic volume，and stroke volume between the HP group and the HDP subgroups（all P<0.05），while the difference in left ventricular ejection fraction was not statistically significant（ P>0.05）. ② Significant differences were identified in strain and TMAD parameters between the HP group and the HDP subgroups（all P<0.05），with LVGLS，AP4 Midpt% and AP2 Midpt% exhibited the largest effect sizes（ η p2=0.457，0.453，0.351）. A progressive decline in strain and TMAD parameters was observed as the severity of HDP increased. ③ There were strong positive correlations between AP4 Midpt%，AP2 Midpt% and LVGLS（ r=0.752，0.747；all P<0.001）. ④ LVGLS，AP4 Midpt% and AP2 Midpt% all demonstrated significant diagnostic efficacies for changes in left ventricular function in HDP（AUC=0.840，0.847，0.791），and the differences in AUC among the 3 curves were not statistically significant（all P>0.05）.⑤ The success rate of collecting TMAD parameters was significantly higher than that of strain parameters（99.24% vs. 93.58%， P<0.001）. Conclusions:As the severity of the disease worsens，the changes of left ventricular structure and function in pregnant women with HDP become more and more significant. Both strain and TMAD parameters can early and sensitively identify the subclinical damage of left ventricular systolic function in HDP pregnant women，and both of them have the same diagnostic value. TMAD parameters can be used as a reliable substitute parameter of LVGLS in HDP pregnant women.

Objective:To investigate the effects of allergens on expressions of IL-18,IL-18BPa and IL-18Rα in blood CD4+Th17 cells of patients with allergic rhinitis and asthma syndrome(ARA)and plasma levels of IL-17A and IL-17F in ARA patients.Methods:ARA patients(n=25)and healthy volunteers(n=22)in the First Affiliated Hospital of Jinzhou Medical University and Henan Provincial People's Hospital were recruited,and blood samples of the subjects were collected.Proportions of CD4+Th17 cells,and effects of allergens on expressions of IL-18,IL-18BPa and IL-18Rα in Th17 cells were determined by flow cytometry.Levels of IL-17A and IL-17F were examined by Bioplex system.Correlation between levels of free plasma free IL-18(fIL-18)and IL-17A,and per-centage of Th17 cells was further analyzed.Results:Proportion of IL-18+cells in Th17 cells was increased in ARA patients by 26.0%(P<0.01),and house dust mite allergen induced 1.22-fold elevation in expression of IL-18 in Th17 cells(P<0.05).In addition,Arte-misiae sieversiana wild pollen allergen enhanced expressions of IL-18 and IL-18Rα in Th17 cells of ARA patients(P<0.05).Plasma levels of IL-17A and IL-17F were increased by 2.2 and 1.1 folds,respectively(P<0.05)in ARA patients,and they correlated well with other(R=0.712,P<0.01).Moreover,the increased level of fIL-18 was moderately correlated with the increased level of IL-17A and the elevated proportion of Th17 cells in ARA patients(r=0.607,r=0.652,P<0.05).Conclusion:The increased plasma fIL-18 in ARA patients may be derived from Th17 cells.Allergens may be involved in pathogenesis of ARA by inducing elevated IL-18 and IL-18Rα expressions in Th17 cells.