OBJECTIVE To investigate the mechanism of Zuogui pill in improving pancreatic β cell function in the offspring of rats with gestational diabetes mellitus （GDM）.METHODS Thirty-six pregnant rats were divided into normal group， model group， insulin glargine group （positive control）， and low-， medium- and high-dose Zuogui pill groups， with 6 rats in each group. The normal group and model group were given intragastric administration of equal-volume normal saline. The insulin glargine group was subcutaneously injected with insulin glargine at an initial dose of 1 U/kg， and the dosage was increased by 1 U per day until random blood glucose returned to normal. The low-， medium- and high-dose Zuogui pill groups were intragastrically administered with Zuogui pill solutions at 4.725， 9.45 and 18.9 g/kg once a day until the birth of offspring. On postnatal day 21 （12 offspring in each group）， body weight， fasting blood glucose （FBG） and oral glucose tolerance test were performed on the offspring. Pancreatic histopathological changes of 60-day-old offspring were observed. The insulin-positive expression area ratio in pancreatic tissue， serum levels of glycated serum protein （GSP）， high-density lipoprotein cholesterol （HDL-C） and low-density lipoprotein cholesterol （LDL-C）， as well as the mRNA and protein relative expression levels of wingless-type MMTV integration site family member 7a（Wnt7a）and glycogen synthase kinase 3β（GSK-3β） in pancreatic tissue were detected.RESULTS Compared with normal group， the body weight， insulin-positive expression area ratio in pancreatic tissue， serum HDL-C level， and the mRNA and protein relative expression levels of Wnt7a in pancreatic tissue were significantly decreased of the offspring in the model group （ P ＜0.05）. Meanwhile， FBG， blood glucose levels at 60， 90 and 120 min after intragastric administration of 20% glucose solution， serum GSP and LDL-C levels， as well as the mRNA and protein relative expression levels of GSK-3β in pancreatic tissue were significantly increased （ P ＜0.05）；mild degeneration and necrosis of islet cells were observed in pancreatic tissue. Compared with the model group， the above-mentioned indexes were significantly reversed in medium- and high-dose Zuogui pill groups （ P ＜0.05）， and pancreatic pathological injury was improved to varying degrees.CONCLUSIONS Zuogui pill may restore the homeostasis of Wnt7a/GSK-3β signaling axis， so as to improve pancreatic β cell function in the offspring of GDM rats.

From the perspective of narrative medicine， focusing on the “three focal points，” integrating the “three elements，” and grounding in the “four relationships，” this study employed a close reading framework of “metaphor， time， space， and voice” to conduct a detailed interpretation on the approach and methodology of the medical narrative in the classic traditional Chinese medical case record Yi’s Medical Case. The close reading revealed that the author of the case record， Yi Dagen， demonstrated exceptional sensitivity to time and space. He excelled in tracing the complete process of disease occurrence and development within the natural rhythms of life， and in discerning the full truth of disease within the unified “body-society-nature” heaven-human field. When facing different subjects in diagnosis and treatment， Yi Dagen consistently rejected one-way knowledge inculcation and instead chose egalitarian dialogue. He was particularly adept at using metaphorical tools to embed obscure medical theories into patients’ disease stories through the form of life experience， thereby building shared medical understanding among different subjects and achieving the “co-creation of meaning” of disease stories. Through a reflective representation of the findings from the close reading， it was argued that Yi Dagen’s diagnostic and therapeutic narrative logic of “pulse-pattern-symptom-treatment” and the metaphorical narrative possessing dual functions of ontological cognition and an interpretive tool were an important means for fostering empathy and facilitating healing， as well as a concentrated manifestation of Yi Dagen’s “patient-centered” medical attitude. Analyzing Yi Dagen’s sophisticated narrative strategies and techniques provides wisdom references for cultivating medical staff’s narrative competence and offers historical insights for the localized development of narrative medicine.

Objective:To explore the distribution and determinants of abnormal blood lipid metabolism among flying personnel with lumbar disc herniation and with different flying hours and to provide data for targeted intervention strategies.Methods:The hospitalization data of 214 male flying personnel was retrospectively analyzed who were admitted to the Air Force Medical Center between September 2020 and September 2023, diagnosed with lumbar intervertebral disc protrusion, and underwent blood lipid testing within 24 h of admission. According to the hours of flying, they were divided into <1 000 h group (45 cases), 1 000-<3 000 h group (107 cases), and ≥3 000 h group (62 cases). The blood lipid biochemical indicators [total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C)], basic information and personal history of the flying personnel were collected. The detection rates of blood lipid metabolism disorders among flying personnel with different durations of flight were compared. The chi-square test for linear trend was used to find out whether there was a trend of linear changes in the detection rates of various blood lipid disorders. The multivariate Logistic regression analysis was conducted to analyze the determinants of abnormal blood lipid metabolism.Results:There were significant differences in age, levels of total cholesterol and low-density lipoprotein cholesterol, and non-HDL-C between flying personnel in different flying hours groups ( F=80.76, 4.67, 4.00, 6.35, P<0.001,=0.010, 0.020, 0.002). The levels of total cholesterol and low-density lipoprotein cholesterol, and non-HDL-C in the 1 000-<3 000 h group were higher than those in the <1 000 h group ( P=0.023, 0.029, 0.003). The total detection rate of elevated triglyceride was the highest (28.04%). There was a significant difference in the detection rate of elevated low-density lipoprotein cholesterol between the 3 groups ( χ2=6.50, P=0.039), which was lower in the 1 000-<3 000 h group than in the <1 000 h group ( P=0.010). The results of the chi-square analysis of linear association showed that with the increase of flight duration, there was a linear decrease in the detection rates of elevated total cholesterol and elevated non-HDL-C ( χ2=4.17, 4.16, P=0.041, 0.041). The univariate Logistic regression analysis showed that compared with the <1 000 h, the 1 000-<3 000 h was an influencing factor for elevated triglyceride ( OR=4.406, 95% CI: 1.604-12.103) and elevated non-HDL-C ( OR=6.217, 95% CI: 1.403-27.551) while body mass index was an influencing factor for elevated total cholesterol ( OR=1.237, 95% CI: 1.055-1.450) and elevated non-HDL-C ( OR=1.298, 95% CI: 1.087-1.548). Current smoking was an influencing factor for elevated triglyceride ( OR=3.214, 95% CI:1.700-6.078) and decreased high-density lipoprotein cholesterol ( OR=3.200, 95% CI: 1.724-5.941). The multivariate Logistic regression analysis showed that body mass index was a risk factor for elevated total cholesterol ( OR=1.245, 95% CI: 1.054-1.471) and elevated non-HDL-C ( OR=1.301, 95% CI: 1.082-1.564). Current smoking was a risk factor for elevated triglyceride ( OR=3.439, 95% CI: 1.550-7.631) and decreased high-density lipoprotein cholesterol ( OR=4.047, 95% CI: 1.901-8.729). Conclusions:Flying personnel with lumbar intervertebral disc protrusion and with different flying hours exhibit distinct features of phased blood lipid metabolism disorders. The triglyceride levels of those with 1 000-<3 000 h deserve more attention while the levels of low-density lipoprotein cholesterol should be brought under control for those with <1 000 h. It is recommended that hierarchical interventions be exercised according to flight stages, and that priority be given to controlling daily adjustable behavioral factors such as body mass index and smoking.

Objective:To explore the distribution and determinants of abnormal blood lipid metabolism among flying personnel with lumbar disc herniation and with different flying hours and to provide data for targeted intervention strategies.Methods:The hospitalization data of 214 male flying personnel was retrospectively analyzed who were admitted to the Air Force Medical Center between September 2020 and September 2023, diagnosed with lumbar intervertebral disc protrusion, and underwent blood lipid testing within 24 h of admission. According to the hours of flying, they were divided into <1 000 h group (45 cases), 1 000-<3 000 h group (107 cases), and ≥3 000 h group (62 cases). The blood lipid biochemical indicators [total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C)], basic information and personal history of the flying personnel were collected. The detection rates of blood lipid metabolism disorders among flying personnel with different durations of flight were compared. The chi-square test for linear trend was used to find out whether there was a trend of linear changes in the detection rates of various blood lipid disorders. The multivariate Logistic regression analysis was conducted to analyze the determinants of abnormal blood lipid metabolism.Results:There were significant differences in age, levels of total cholesterol and low-density lipoprotein cholesterol, and non-HDL-C between flying personnel in different flying hours groups ( F=80.76, 4.67, 4.00, 6.35, P<0.001,=0.010, 0.020, 0.002). The levels of total cholesterol and low-density lipoprotein cholesterol, and non-HDL-C in the 1 000-<3 000 h group were higher than those in the <1 000 h group ( P=0.023, 0.029, 0.003). The total detection rate of elevated triglyceride was the highest (28.04%). There was a significant difference in the detection rate of elevated low-density lipoprotein cholesterol between the 3 groups ( χ2=6.50, P=0.039), which was lower in the 1 000-<3 000 h group than in the <1 000 h group ( P=0.010). The results of the chi-square analysis of linear association showed that with the increase of flight duration, there was a linear decrease in the detection rates of elevated total cholesterol and elevated non-HDL-C ( χ2=4.17, 4.16, P=0.041, 0.041). The univariate Logistic regression analysis showed that compared with the <1 000 h, the 1 000-<3 000 h was an influencing factor for elevated triglyceride ( OR=4.406, 95% CI: 1.604-12.103) and elevated non-HDL-C ( OR=6.217, 95% CI: 1.403-27.551) while body mass index was an influencing factor for elevated total cholesterol ( OR=1.237, 95% CI: 1.055-1.450) and elevated non-HDL-C ( OR=1.298, 95% CI: 1.087-1.548). Current smoking was an influencing factor for elevated triglyceride ( OR=3.214, 95% CI:1.700-6.078) and decreased high-density lipoprotein cholesterol ( OR=3.200, 95% CI: 1.724-5.941). The multivariate Logistic regression analysis showed that body mass index was a risk factor for elevated total cholesterol ( OR=1.245, 95% CI: 1.054-1.471) and elevated non-HDL-C ( OR=1.301, 95% CI: 1.082-1.564). Current smoking was a risk factor for elevated triglyceride ( OR=3.439, 95% CI: 1.550-7.631) and decreased high-density lipoprotein cholesterol ( OR=4.047, 95% CI: 1.901-8.729). Conclusions:Flying personnel with lumbar intervertebral disc protrusion and with different flying hours exhibit distinct features of phased blood lipid metabolism disorders. The triglyceride levels of those with 1 000-<3 000 h deserve more attention while the levels of low-density lipoprotein cholesterol should be brought under control for those with <1 000 h. It is recommended that hierarchical interventions be exercised according to flight stages, and that priority be given to controlling daily adjustable behavioral factors such as body mass index and smoking.

Objective:To understand the current situation and the relevant factors of the intrinsic capacity of the elderly in nursing institutions.Methods:It was a cross-sectional study. From December 2023 to February 2024, a total of 10 elderly people living in 5 institutions in Huaihua City, Hunan Province, 3 institutions in Changsha City, and 2 institutions in Yinchuan City, Ningxia Hui Autonomous Region, were conveniently selected. Relevant clinical data of the participants were collected through questionnaires. The 5 dimensions of motor, psychological, cognitive, vitality, and perceptual were selected to evaluate the intrinsic capacity of the participants, and their total intrinsic capacity scores were calculated by using the Short Physical Performance Battery, Geriatric Depression Scale, Mini-mental State Examination, Short-Form Mini-Nutritionalas Assessment and the Complaints Sensory Functioning, respectively. Multiple linear stepwise regression models were used to analyze the correlates of intrinsic competence in older adults in nursing facilities.Results:Two hundred and seventy institutionalized older adults were included in the analysis, aged (80.9±8.5) years, 117(43.33%) were male, and the length of residence in an institution was 1.50(0.83, 3.00) years.The intrinsic capacity score of the 270 institutionalized older adults was 2.24±0.97, of which 265(98.15%) had declining intrinsic capacity and 5(1.85%) had good intrinsic capacity. The results of multiple linear stepwise regression analysis showed that literacy level, economic source, occupation, frequency of exercise, use of smartphones, use of elderly mobility aids, and whether or not the elderly living in the nursing home received financial support from the state were independently associated with the intrinsic ability of the elderly living in the nursing home (all P<0.05). Conclusions:The overall level of intrinsic capacity of the investigated elderly in nursing homes is low, and literacy level, economic source, occupation, use of smartphones, use of elderly mobility aids, and whether the nursing home receives state financial support are independent correlates of the intrinsic ability of the elderly in nursing homes.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Objective:To investigate the impact of imaging anatomical features on the prognosis of middle-aged and elderly patients with anomalous coronary artery originating from the opposite sinus (ACAOS).Methods:This retrospective cohort study enrolled patients aged ≥45 years who were diagnosed with ACAOS by coronary computed tomography angiography (CTA) at the Affiliated Hospital of Xuzhou Medical University between January 1, 2011, and December 31, 2018. Baseline clinical data and coronary CTA images were collected. Anatomic imaging features were extracted, including ACAOS subtype, course of the anomalous vessel, and ostial angle. The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of acute myocardial infarction, cardiac death, and coronary revascularization. The Maxstat method was used to determine the cut-off values of specific anatomical features for predicting MACE risk. Cox proportional hazards models were employed to analyze the impact of these imaging features on MACE in middle-aged and elderly ACAOS patients.Results:A total of 203 patients were enrolled, aged (60.0(51.0, 66.0)) years, including 119 (58.6%) males. Over a follow-up of (98.2±30.9) months, 39 patients experienced MACE. Maxstat identified an optimal cut-off value of 34.3° for the ostial angle of the anomalous vessel. Multivariable Cox proportional hazards regression analysis revealed that the following factors were independent risk factors for MACE: left-sided ACAOS subtype ( HR=4.35, 95% CI 2.17-8.73, P<0.001), an interarterial course between the aorta and pulmonary artery ( HR=3.21, 95% CI 1.23-8.37, P=0.017), an anomalous vessel ostial angle <34.3° ( HR=2.62, 95% CI 1.18-5.77, P=0.017), and concomitant coronary artery disease ( HR=2.92, 95% CI 1.49-5.73, P=0.002). Conclusion:In middle-aged and elderly patients with ACAOS, the imaging anatomical features of a left-sided ACAOS subtype, an interarterial course, and an ostial angle <34.3° are independent risk factors for MACE.

Objective:To investigate the safety and efficacy of urinary microbiota transplantation（UMT）in treating interstitial cystitis（IC）.Methods:A retrospective analysis of the clinical data of three patients with IC treated with UMT at the Central Hospital of Jiangnan University from May 2022 to August 2024. Three women（45，62，79 years）presented with urinary frequency（10 - 90 min intervals），urgency，dysuria，lower abdominal pain，and non-organic sleep disorder，with nocturia（2 - 15 episodes）causing sleep difficulty. Disease durations were 3，6，and 21 years. Prior antibiotic therapy failed. Preoperative urinalysis/culture（x2）ruled out bacterial cystitis，and diagnosed as interstitial cystitis（IC），with one of transient positive urine culture. Preoperative scores for case 1 were self-rating depression scale（SDS）of 49，self-rating anxiety scale（SAS）of 31，interstitial cystitis symptom index（ICSI）of 5，interstitial cystitis problem index（ICPI）of 2，brief urological problem scale of 50，genitourinary pain assessment scale of 10，and pain catastrophizing scale（PCS）of 0. For case 2，the scores were 60 of SDS，66 of SAS，9 of ICSI，11 of ICPI，50 of brief urological problem scale，28 of genitourinary pain assessment scale，and 34 of PCS. For case 3，the scores were 44 of SDS，48 of SAS，11 of ICSI，5 of ICPI，33 of brief urological problem scale，27 of genitourinary pain assessment scale，and 21 of PCS. Preoperative bladder hydro-distention showed mucosal hemorrhage including central block hemorrhage（Case 1），numerous spots（Case 2），and distinct sheets（Case 3）. Preoperative urine 16S rRNA sequencing revealed low diversity，increased Gardnerella/ Bacteroides（opportunistic），and decreased Bacillus/ Streptococcus（beneficial）. Two healthy young female donors had normal comprehensive tests covering blood/urine/stool，coagulation，CRP，immunity，liver/kidney function，lipids，infectious diseases，hormones，tumor markers，urine culture，TOUCH，and expanded quantitative urine culture. Donor urine 16S rRNA showed low pathogenic（ Gardnerella/ Bacteroides）abundance. Donor midstream morning urine was catheter-collected，centrifuged，and the bacterial pellet resuspended in saline. Recipients underwent bladder irrigation pre-UMT. On UMT day，donor bacterial suspension was instilled via catheter with adverse event monitoring. Follow-up included clinic visits at 1 month and 1 year for symptom assessment，scale scoring，cystoscopy evaluating mucosal inflammation，hydrodistension checks，and telephone tracking of urinary symptoms every 2 - 3 months. Prognosis was assessed by symptom relief，scale score reduction，and mucosal recovery. Results:No adverse reactions occurred within 24 hours post-UMT in all 3 cases. Two patients showed same-day urinary urgency reduction；three reported relief from urinary frequency/urgency on postoperative day 7，with 2 - 3 hour daytime intervals and 0 - 5 nocturnal voids. Two patients experienced lower abdominal pain alleviation. Postoperative Week 1 urinalysis and urine cultures revealed no abnormalities. The 16S rRNA test showed a decrease in the abundance of harmful bacteria（e.g.， Cupriavidus，Ureaplasm，Mycobacterium，Pseudomonas）and an increase in the abundance of beneficial bacteria（ Dietzia，Halomonas，and Streptococcus），and the overall urobacterial structure was significantly improved and similar to that of the donor. Case 1 was followed up for 20 months，and the lab tests were normal，with SDS scales of 38，SAS of 20，ICSI of 3，ICPI of 2，brief urological problem scale of 44，genitourinary pain assessment scale of 10，PCS of 0，at 9 months post-op follow-up，indicating physical and mental improvement. The bladder hydro-distention revealed intact mucosa with only mild inflammation，which improved versus preoperative situation. Case 2 was followed up for 15 months，and the lab tests were normal，with SDS scales of 44，SAS of 34，ICSI of 4，ICPI of 2，brief scale of urinary problems of 0，genitourinary pain assessment scale of 9，PCS of 7，at 2 months post-op follow-up，showing improved anxiety/depression and quality of life. The hydro-distention showed decreased scattered hemorrhagic dots and mucosal inflammation. Case 3 was followed up for 13 months，with an increased leukocytes of urine and the other being normal for lab tests，and SDS scales of 35，SAS of 46，ICSI of 13，ICPI of 13，brief scale of urinary problems of 10，genitourinary pain assessment scale of 33，PCS of 11，at 13 months post-op follow-up，indicating physical and mental improvement. The hydro-distention revealed mucosal congestion，marked submucosal vasodilation，and inflammation decreased compared with preoperative situation. Conclusions:UMT alleviates urinary frequency，urgency，and pain in IC patients with sustained effects，significantly improves urine microecology，and shows no adverse events，positioning it as a viable intervention for IC.

ObjectiveTo investigate the effect and mechanism of Sishenwan in restoring the intestinal barrier function in the rat model of diarrhea-predominant irritable bowel syndrome （IBS-D） due to spleen-kidney Yang deficiency based on intestinal flora and short-chain fatty acids. MethodsAfter the delivery of 10 SPF-grade pregnant rats， 4 male suckling rats were kept in each litter for the experiment. The male suckling rats were randomly allocated into blank， model， low-dose （3.51 g·kg^-1） Sishenwan， high-dose （7.02 g·kg^-1） Sishenwan， and Peifeikang （0.54 g·kg^-1） groups， with 8 rats in each group. The blank group was fed conventionally， and the other groups were subjected to mother-child separation and Sennae Folium gavage （1 g·mL^-1， 10 mL·kg^-1） for the modeling of IBS-D due to spleen-kidney Yang deficiency. After the modeling was completed， the rats in Sishenwan groups were administrated with the corresponding dose of Sishenwan decoction by gavage， and the Peifeikang group with bifidobacterium triple live powder+normal saline suspension. The blank and model groups were treated with an equal volume of normal saline by gavage. The general conditions and fecal characteristics of rats were observed. After 2 weeks of administration， the rats were anesthetized for sample collection. The pathological changes of the colon tissue in rats were observed by hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was employed to measure the levels of transforming growth factor-beta （TGF-β）， interleukin-10 （IL-10）， and interleukin-22 （IL-22）. Immumohistochemical staining （IHC） was performed to detect the positive expression of zonula occludens-1 （ZO-1） and occludin in the colon tissue. Western blot was employed to determine the protein levels of ZO-1 and occludin in the colon tissue of rats， and 16S rRNA gene sequencing was performed for intestinal flora. Gas chromatography-mass spectrometry was employed to determine the content of short-chain fatty acids （SCFAs） in the cecum contents of rats. ResultsThe colon tissue in the blank group presented a clear structure， neat glands， and no inflammatory cell infiltration. In the model group， the colon tissue showcased a disorganized structure， irregular arrangement of glands， and inflammatory cell infiltration. Compared with the model group， the low-dose and high-dose Sishenwan groups and the Peifeikang group exhibited an intact colon tissue structure， regular arrangement of glands， and reduced inflammatory cell infiltration. Compared with the blank group， the modeling lowered the levels of TGF-β， IL-10， and IL-22 in the serum （P<0.01）， down-regulated the protein levels of ZO-1 and occludin in the colon tissue （P<0.01）， and decreased the content of acetic acid and propionic acid and increased the content of butyric acid in cecum contents （P<0.05）. Compared with the model group， low-dose and high-dose Sishenwan raised the levels of TGF-β， IL-10， and IL-22 in the serum （P<0.05， P<0.01）， and Peifeikang elevated the levels of TGF-β and IL-10 in the serum （P<0.01）. High-dose Sishenwan and Peifeikang up-regulated the protein levels of ZO-1 and occludin （P<0.05， P<0.01）， increased the content of acetic acid and propionic acid in cecum contents （P<0.05）， and decreased the content of butyric acid （P<0.05）. The 16S rRNA gene sequencing results showed that the intestinal flora structure of the model group changed compared with that of the blank group. Compared with the model group， Sishenwan and Peifeikang increased the relative abundance of Lachnospiraceae， Muribaculaceae， Akkermansiaceae， Ligilactobacillus， UBA3282， Akkermansia， and Corynebacterium while reducing the relative abundance of Oscillospiraceae， Desulfovibrionaceae， Lactobacillus， Romboutsia， and Desulfovibrio. They can restore the intestinal flora structure similar to that in the blank group. ConclusionSishenwan can alleviate diarrhea symptoms and colonic mucosal inflammation， increase the expression of tight junction proteins in the colonic mucosa， and strengthen the intestinal barrier in IBS-D rats with the syndrome of spleen-kidney Yang deficiency. The mechanism of action may be related to optimizing the structure and balance of intestinal flora and regulating the SCFAs， and the effect of high-dose Sishenwan is obvious.