ObjectiveTo investigate the therapeutic efficacy of Danggui Shaoyaosan （DSS） on renal injury in db/db mice and its impact on endoplasmic reticulum stress （ERS） in renal tissues. MethodsThirty 8-week-old male db/db mice and six db/m mice were acclimated for one week， after which urinary microalbumin and blood glucose levels were monitored to establish a diabetic kidney disease （DKD） model. The model mice were randomly divided into a model group， an irbesartan group， and three DSS treatment groups with different doses （16.77， 33.54， and 67.08 g·kg^-1·d^-1）. A normal group was set as control. Each group was intragastrically administered with the corresponding drugs or saline for 8 weeks. After the intervention， general conditions were observed. Serum cystatin C （Cys-C）， 24-hour urinary total protein （24 h-UTP）， 24-hour urinary microalbumin （24 h-UMA）， urinary creatinine （Ucr）， and urea nitrogen （UUN） were measured. Transmission electron microscopy （TEM） was used to observe glomerular basement membrane （GBM） and ultrastructural changes of the endoplasmic reticulum （ER） in glomerular endothelial cells. Western blot， real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and immunohistochemistry were used to analyze renal tissue structure and the expression of GRP78， CHOP， and related markers. ResultsCompared with the normal group， the mice in the model group showed curled posture， sluggish response， poor fur condition， increased levels of Cys-C， 24 h-UTP， 24 h-UMA， and UUN （P<0.05）， while Ucr decreased （P<0.05）. The GBM was significantly thickened， with podocyte and foot process fusion. The protein expressions of GRP78， CHOP， and ATF6 were significantly upregulated （P<0.05）， the mRNA levels of GRP78 and CHOP increased （P<0.05）， and immunohistochemistry showed an enhanced GRP78 signal （P<0.05）. After treatment， the mice exhibited improved behavior， normalized GBM and podocyte structure， improved ER morphology and markedly better biochemical indicators. Western blot， Real-time PCR， and immunohistochemistry indicated that the ERS-related markers were downregulated in the DSS treatment groups （P<0.05）， suggesting alleviated ERS and improved renal function. ConclusionDSS can effectively ameliorate renal pathological damage in db/db mice， possibly by regulating ERS in glomerular endothelial cells， although the underlying signaling mechanisms require further investigation.

Objective To explore the mechanism by which breast cancer-derived LncRNA OIP5-AS1 regulates the migration, invasion, and epithelial-mesenchymal transition of breast cancer cells through the M2 polarization of tumor-associated macrophages (TAM). Methods MDA-MB-231 cells were divided into the control group (blank control), the NC group (transfected with NC siRNA), and the si-OIP5 group (transfected with LncRNA OIP5-AS1 siRNA). The mRNA expression levels of LncRNAs OIP5-AS1, IL-4, and IL-13 were detected by RT-qPCR. The protein expression levels of IL-4 and IL-13 in the culture supernatant were detected by ELISA. The culture supernatant from the control group was added to RPMI 1640 medium at different volume ratios to induce the polarization of M0 macrophages into TAMs. The mRNA expression of CD206 in TAMs was detected by RT-qPCR. M0-type macrophages were induced with the medium supernatant of the NC group/si-OIP5 group, and the expression of CD206 was detected by Western blot. Subsequently, a co-culture model of macrophage and MDA-MB-231 was constructed to evaluate the migration and invasion abilities of MDA-MB-231 cells and detect the expression changes in Vimentin, N-cadherin and E-cadherin. Results Compared with the control and NC groups, the si-OIP5 group showed significantly downregulated expression of LncRNA OIP5-AS1 (P<0.001) and significantly decreased IL-13 mRNA and protein levels (P<0.05). Meanwhile, no significant difference was observed in the expression of IL-4 among the groups. Conditioned medium induced CD206 expression in M0 macrophages in a volume-dependent manner, with the strongest effect at a 40% volume ratio (P<0.001). The CD206 protein level in the si-OIP5 group significantly decreased (P<0.01). In the co-culture system, the migration and invasion abilities of MDA-MB-231 cells in the si-OIP5 group significantly weakened (P<0.001), the expression of E-cadherin was upregulated, and the expression levels of N-cadherin and Vimentin were downregulated (both P<0.01). Conclusion Breast cancer-derived LncRNA OIP5-AS1 can induce TAM M2 polarization mediated by IL-13, thereby promoting the migration, invasion, and EMT of breast cancer cells.

BACKGROUND:A network-based pharmacological approach has identified multifunctional effects of the main bioactive compounds in the Trichosanthis Fructus-Allii Macrostemonis Bulbus on coronary heart disease;however,the mechanism of its therapeutic effect on coronary heart disease has not been fully elucidated. OBJECTIVE:To investigate the role and mechanism of Trichosanthis Fructus-Allii Macrostemonis Bulbus in improving coronary heart disease by regulating the composition of gut microbiota. METHODS:Forty Sprague-Dawley rats were randomly divided into four groups:blank control group(n=10),model group(n=10),positive drug group(n=10),and medicine pair group(n=10).A rat model of coronary heart disease was established by continuous gastric perfusion of fat emulsion and injection of pituitrin.After modeling,rats in the model group were gavaged with distilled water(10 mL/kg)for control,rats in the positive drug group were gavaged with simvastatin 4 mg/kg per day,and rats in the medicine pair group were gavaged with Trichosanthis Fructus-Allii Macrostemonis Bulbus pairs 7.56 g/kg per day.All interventions lasted for 14 days.Electrocardiograms and myocardial pathology were observed,and blood lipid levels were measured.The structure of gut microbiota was analyzed using 16S rDNA sequencing technology. RESULTS AND CONCLUSION:Electrocardiogram results showed ST segment elevation in the model group.There were no significant abnormalities in the electrocardiograms of the positive drug group and medicine pair group.Compared with the blank control group,the levels of total cholesterol,triacylglycerol,and low-density lipoprotein cholesterol were significantly higher in the model group(P<0.05).Compared with the model group,the levels of total cholesterol,triacylglycerol,and low-density lipoprotein cholesterol were significantly lower in the positive drug group and medicine pair group(P<0.05).Compared with the blank control group,focal myocardial cell necrosis was observed in the model group,while partial myocardial cell disarray was observed in the positive drug group and medicine pair group.Compared with the blank control group,the Ace,Shannon,and Chao indices were increased(P<0.05)and the Simpson index was decreased(P<0.05)in the model group,positive drug group and medicine pair group.Compared with the model group,the Ace and Chao indices were decreased(P<0.05),while the Shannon index showed no significant difference(P>0.05)and the Simpson index was also decreased(P<0.05)in the positive drug group and medicine pair group.Compared with the blank control group,the relative abundances of Desulfovibrionia,Muribaculaceae_norank,etc.were increased in the model group,while those of Clostridia,[Eubacterium]_coprostanoligenes_group_norank,etc.were decreased.Compared with the model group,the relative abundances of WPS-2_norank,Muribaculaceae_norank,etc.were increased in the medicine pair group,while those of Clostridia,[Eubacterium]_coprostanoligenes_group_norank,etc.were decreased;the relative abundances of Desulfobacterota,[Eubacterium]_coprostanoligenes_group_norank,etc.were increased in the positive drug group,while those of Firmicutes,Muribaculaceae_norank,etc.were decreased.Compared with the positive drug group,the relative abundances of Desulfobacterota,Bacteroides,etc.were increased in the medicine pair group,while those of Firmicutes,[Eubacterium]_coprostanoligenes_group_norank,etc.were decreased.The LEfSe results showed that the medicine pair group had the highest microbial enrichment,followed by the blank control group and positive drug group,with the model group having the lowest microbial enrichment.To conclude,Trichosanthis Fructus-Allii Macrostemonis Bulbus pairs can improve the development of coronary heart disease by regulating gut microbiota composition,providing new insights for further research and development of Trichosanthis Fructus-Allii Macrostemonis Bulbus pairs.

Objective To explore the relationship between PANoptosis and hepatic ischemia-reperfusion injury (HIRI), and to screen the key genes of PANoptosis in HIRI. Methods PANoptosis-related differentially expressed genes (PDG) were obtained through the Gene Expression Omnibus database and GeneCards database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the biological pathways related to PDG. A protein-protein interaction network was constructed. Key genes were selected, and their diagnostic value was assessed and validated in the HIRI mice. Immune cell infiltration analysis was performed based on the cell-type identification by estimating relative subsets of RNA transcripts. Results A total of 16 PDG were identified. GO analysis showed that PDG were closely related to cellular metabolism. KEGG analysis indicated that PDG were mainly enriched in cellular death pathways such as apoptosis and immune-related signaling pathways such as the tumor necrosis factor signaling pathway. GSEA results showed that key genes were mainly enriched in immune-related signaling pathways such as the mitogen-activated protein kinase (MAPK) signaling pathway. Two key genes, DFFB and TNFSF10, were identified with high accuracy in diagnosing HIRI, with areas under the curve of 0.964 and 1.000, respectively. Immune infiltration analysis showed that the control group had more infiltration of resting natural killer cells, M2 macrophages, etc., while the HIRI group had more infiltration of M0 macrophages, neutrophils, and naive B cells. Real-time quantitative polymerase chain reaction results showed that compared with the Sham group, the relative expression of DFFB messenger RNA in liver tissue of HIRI group mice increased, and the relative expression of TNFSF10 messenger RNA decreased. Cibersort analysis showed that the infiltration abundance of naive B cells was positively correlated with DFFB expression (r=0.70, P=0.035), and the infiltration abundance of M2 macrophages was positively correlated with TNFSF10 expression (r=0.68, P=0.045). Conclusions PANoptosis-related genes DFFB and TNFSF10 may be potential biomarkers and therapeutic targets for HIRI.

BACKGROUND: While emotional distress, encompassing anxiety and depression, has been associated with negative clinical outcomes, its impact across various clinical departments and general hospitals has been less explored. Previous studies with limited sample sizes have examined the effectiveness of specific treatments (e.g., antidepressants) rather than a systemic management strategy for outcome improvement in non-psychiatric inpatients. To enhance the understanding of the importance of addressing mental health care needs among non-psychiatric patients in general hospitals, this study retrospectively investigated the impacts of emotional distress and the effects of early detection and management of depression and anxiety on hospital length of stay (LOS) and rate of long LOS (LLOS, i.e., LOS >30 days) in a large sample of non-psychiatric inpatients. METHODS: This retrospective cohort study included 487,871 inpatients from 20 non-psychiatric departments of a general hospital. They were divided, according to whether they underwent a novel strategy to manage emotional distress which deployed the Huaxi Emotional Distress Index (HEI) for brief screening with grading psychological services (BS-GPS), into BS-GPS ( n = 178,883) and non-BS-GPS ( n = 308,988) cohorts. The LOS and rate of LLOS between the BS-GPS and non-BS-GPS cohorts and between subcohorts with and without clinically significant anxiety and/or depression (CSAD, i.e., HEI score ≥11 on admission to the hospital) in the BS-GPS cohort were compared using univariable analyses, multilevel analyses, and/or propensity score-matched analyses, respectively. RESULTS: The detection rate of CSAD in the BS-GPS cohort varied from 2.64% (95% confidence interval [CI]: 2.49%-2.81%) to 20.50% (95% CI: 19.43%-21.62%) across the 20 departments, with a average rate of 5.36%. Significant differences were observed in both the LOS and LLOS rates between the subcohorts with CSAD (12.7 days, 535/9590) and without CSAD (9.5 days, 3800/169,293) and between the BS-GPS (9.6 days, 4335/178,883) and non-BS-GPS (10.8 days, 11,483/308,988) cohorts. These differences remained significant after controlling for confounders using propensity score-matched comparisons. A multilevel analysis indicated that BS-GPS was negatively associated with both LOS and LLOS after controlling for sociodemographics and the departments of patient discharge and remained negatively associated with LLOS after controlling additionally for the year of patient discharge. CONCLUSION Emotional distress significantly prolonged the LOS and increased the LLOS of non-psychiatric inpatients across most departments and general hospitals. These impacts were moderated by the implementation of BS-GPS. Thus, BS-GPS has the potential as an effective, resource-saving strategy for enhancing mental health care and optimizing medical resources in general hospitals.
Humans ; Retrospective Studies ; Male ; Length of Stay/statistics & numerical data* ; Female ; Middle Aged ; Adult ; Psychological Distress ; Inpatients/psychology* ; Aged ; Anxiety/diagnosis* ; Depression/diagnosis*

BACKGROUND: The profile and clinical significance of the oral microbiome in patients with non-obstructive hypertrophic cardiomyopathy (noHCM) and obstructive hypertrophic cardiomyopathy (oHCM) remain unexplored. The objective of this study was to evaluate the difference of oral microbiome between noHCM and oHCM patients. METHODS: This cross-sectional study enrolled 18 noHCM patients and 26 oHCM patients from Fuwai Hospital, Chinese Academy of Medical Sciences between 2020 and 2021. Clinical and periodontal evaluations were conducted, and subgingival plaque samples were collected. Metagenomic sequencing and subsequent microbial composition and functional analyses were performed. RESULTS: Compared to oHCM patients, those with noHCM had higher systolic blood pressure (138.1 ± 18.8 mmHg vs . 124.2 ± 13.8 mmHg, P = 0.007), a larger body circumference (neck circumference: 39.2 ± 4.0 cm vs . 35.1 ± 3.7 cm, P = 0.001; waist circumference: 99.7 ± 10.5 cm vs . 92.2 ± 10.8 cm, P = 0.027; hip circumference: 102.5 ± 5.6 cm vs . 97.5 ± 9.1 cm, P = 0.030), a greater left ventricular end-diastolic diameter (46.6 ± 4.9 mm vs . 43.1 ± 4.9 mm, P = 0.026), and a lower left ventricular ejection fraction (64.1 ± 5.7 % vs . 68.5 ± 7.8%, P = 0.048). While overall biodiversity and general microbial composition were similar between the noHCM and oHCM groups, ten taxa displayed significant differences at the genus and species levels, with Porphyromonas gingivalis showing the highest abundance and greater enrichment in noHCM (relative abundance: 7.79535 vs . 4.87697, P = 0.043). Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis identified ten distinct pathways, with pathways related to energy and amino acid metabolism being enriched in oHCM patients, and those associated with genetic information processing less abundant in the oHCM group. Metabolic potential analysis revealed ten significantly altered metabolites primarily associated with amino sugar and nucleotide sugar metabolism, porphyrin metabolism, pentose and glucuronate interconversion, and lysine degradation. CONCLUSIONS The higher abundance of Porphyromonas gingivalis , which is known to impact cardiovascular health, in noHCM patients may partially account for clinical differences between the groups. Pathway enrichment and metabolic potential analyses suggest microbial functional shifts between noHCM and oHCM patients, potentially reflecting inherent metabolic changes in HCM.
Humans ; Cardiomyopathy, Hypertrophic/microbiology* ; Female ; Male ; Microbiota/genetics* ; Middle Aged ; Cross-Sectional Studies ; Adult ; Mouth/microbiology* ; Aged

Objective: To investigate the objective characteristics of tongue manifestation in different stages of damp-heat syndrome in diabetic kidney disease (DKD). Methods: A cross-sectional study enrolled 134 patients with DKD G3-5 stages who met the diagnostic criteria for damp-heat syndrome in DKD. The patients were treated at Dongzhimen Hospital, Beijing University of Chinese Medicine, from May 2023 to January 2024. The patients were divided into three groups: DKD G3, DKD G4, and DKD G5 stage, with 53, 33, and 48 patients in each group, respectively. Clinical general data (gender, age, and body mass index) and damp-heat syndrome scores were collected from the patients. The YZAI-02 traditional Chinese medicine (TCM) AI Tongue Image Acquisition Device was used to capture tongue images from these patients. The accompanying AI Open Platform for TCM Tongue Diagnosis of the device was used to analyze and extract tongue manifestation features, including objective data on tongue color, tongue quality, coating color, and coating texture. Clinical data and objective tongue manifestation characteristics were compared among patients with DKD G3-5 based on their DKD damp-heat syndrome status. Results: No statistically significant difference in gender or body mass index was observed among the three patient groups. The DKD G3 stage group had the highest age (P<0.05). The DKD G3 stage group had a lower score for symptoms of poor appetite and anorexia(P<0.05) than the DKD G5 group. No statistically significant difference was observed in damp-heat syndrome scores among the three groups. Compared with the DKD G5 stage group, the DKD G3 stage group showed a decreased proportion of pale color at the tip and edges of the tongue (P<0.05). The DKD G4 stage group exhibited an increased proportion of crimson at the root of the tongue, a decreased proportion of thick white tongue coating at the root, a decreased proportion of pale color at the tip and edges of the tongue, an increased hue value (indicating color tone) of the tongue color in the middle, an increased brightness value (indicating color lightness) of the tongue coating color in the middle, and an increased thickness of the tongue coating (P<0.05). No statistically significant difference was observed in other tongue color proportions, color chroma values, body characteristics, coating color proportions, coating color chroma values, and coating texture characteristics among the three groups. Conclusion Tongue features differ in different stages of DKD damp-heat syndrome in multiple dimensions, enabling the inference that during the DKD G5 stage, the degree of qi and blood deficiency in the kidneys, heart, lungs, liver, gallbladder, spleen, and stomach is prominent. Dampness is more likely to accumulate in the lower jiao, particularly in the kidneys, whereas heat evil in the spleen and stomach is the most severe. These insights provide novel ideas for the clinical treatment of DKD.

ObjectiveTo investigate the incidence rate of primary liver cancer （PLC） and the progression of liver fibrosis in chronic hepatitis B （CHB） patients with low-level viremia （LLV） （HBV DNA<2 000 IU/mL but ≥20 IU/mL） after treatment adjustment， and to provide more robust evidence for clinical practice. MethodsA retrospective analysis was performed for the clinical data of LLV patients who initially received nucleos（t）ide analogue （NAs） for at least 48 weeks at the Fifth Medical Center of PLA General Hospital from August 2007 to April 2017 and subsequently underwent NAs adjustment due to LLV， and according to the virologic response after 48 weeks of treatment adjustment， the patients were divided into LLV group and complete virological response （CVR） group （HBV DNA<20 IU/mL）. The patients were followed up once every 3‍ ‍—‍ ‍6 months till the primary endpoint event of PLC or October 2024. The incidence rate of PLC and the progression of liver fibrosis were observed， and the progression of liver fibrosis was defined as an increase of ≥1 grade in fibrosis-4 （FIB-4） index. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups； the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to calculate the cumulative incidence rate of PLC， and the Log-rank test was used for comparison between groups； the Cox regression analysis was used to investigate the risk factors for PLC， and the Logistic regression analysis was used to investigate the influencing factors for the progression of liver fibrosis. ResultsA total of 307 patients were enrolled， with a mean age of 50.0 years， and the male patients accounted for 80.5%. After 48 weeks of treatment with the adjusted NAs regimen， 254 patients （82.7%） achieved CVR， and 53 patients （17.3%） still had LLV. For the LLV group， the incidence rate of PLC was 30.2% and the rate of liver fibrosis progression was 22.6%， while for the CVR group， the incidence rate of PLC was only 13.4%， and the rate of liver fibrosis progression was 7.5%. The multivariate regression analyses showed that LLV was an independent risk factor for the onset of PLC （hazard ratio=2.623， 95% confidence interval ［CI］： 1.315‍ ‍—‍ ‍5.234， P=0.006） and the progression of liver fibrosis （odds ratio=3.213， 95%CI： 1.385‍ ‍—‍ ‍7.455， P=0.007）. ConclusionActive adjustment of treatment is needed immediately after the diagnosis of LLV to improve CVR， and if LLV persists after treatment adjustment， it is necessary to enhance the monitoring of liver fibrosis progression and PLC， so as to facilitate early diagnosis and treatment.