ObjectiveTo study on the different therapeutic effects and potential mechanisms of Rhei Radix et Rhizoma（RH） before and after steaming with wine on constipation model mice. MethodsFifty-four male ICR mice were randomly divided into control group， model group， lactulose group（1.5 mg·kg^-1）， high， medium and low dose groups of RH and RH steaming with wine（PRH）（8， 4， 1 g·kg^-1）. Except for the control group， the constipation model was replicated by gavage of loperamide hydrochloride（6 mg·kg^-1） in the other groups. After 2 weeks of modeling， each administration group was gavaged with the corresponding dose of drug solution， and the control and model groups were given an equal volume of normal saline， 1 time/d for 2 consecutive weeks. After administration， the feces were collected for 16S rRNA sequencing， the levels of gastrin（GAS）， motilin（MTL）， interleukin-6（IL-6）， γ-interferon（IFN-γ） in the colonic tissue were detected by enzyme-linked immunosorbent assay（ELISA）， the histopathological changes of colon were observed by hematoxylin-eosin（HE） staining， flow cytometry was used to detect the proportion changes of CD4⁺， CD8⁺ and regulatory T cell（Treg） in peripheral blood. ResultsCompared with the control group， the model group showed significantly decrease in fecal number in 24 h， fecal quality and fecal water rate（P<0.01）， the colon was seen to have necrotic shedding of mucosal epithelium， localized intestinal glands in the lamina propria were degenerated， necrotic and atrophied， a few lymphocytes were seen to infiltrate in the necrotic area in a scattered manner， the contents of GAS and MTL， the proportions of CD4⁺， CD8⁺ and Treg were significantly reduced（P<0.01）， the contents of IL-6 and IFN-γ were significantly elevated（P<0.05， P<0.01）. Compared with the model group， the fecal number in 24 h， fecal quality and fecal water rate of high-dose groups of RH and PRH were significantly increased（P<0.05， P<0.01）， the pathological damage of the colon was alleviated to varying degrees， the contents of GAS， MTL， IL-6 and IFN-γ were significantly regressed（P<0.05， P<0.01）， and the proportions of CD4⁺ and CD8⁺ were significantly increased（P<0.01）， although the proportion of Treg showed an upward trend， there was no significant difference. In addition， the results of intestinal flora showed that the number of amplicon sequence variant（ASV） and Alpha diversity were decreased in the model group compared with the control group， and there was a significant difference in Beta diversity， with a decrease in the relative abundance of Lactobacillus and an increase in the relative abundances of Bacillus and Helicobacter. Compared with the model group， the ASV number and Alpha diversity were increased in the high-dose groups of RH and PRH， and there was a trend of regression of Beta diversity to the control group， the relative abundance of Lactobacillus increased， and the relative abundances of Bacillus and Helicobacter decreased. ConclusionRH and PRH can improve dysbacteriosis， promote immune system activation， inhibit the release of inflammatory factors for enhancing the gastrointestinal function， which may be one of the potential mechanisms of their therapeutic effect on constipation.

AIM:To analyze differential proteins associated with the pathogenesis of dry eye(DE)using bioinformatics methods, in order to reveal their potential molecular mechanisms.METHODS: Articles published in PubMed and EMBASE databases from the inception of the database to August 31, 2023, that used proteomic methods to detect protein expression in clinical samples of dry eye were searched. Differential proteins were selected and further analyzed using the STRING database and Cytoscape software for hub gene screening and module analysis. Protein-protein interaction(PPI)analysis, gene ontology(GO)functional annotation, and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed.RESULTS: A total of 21 articles were included, identifying 74 differentially expressed proteins. The most frequently occurring differential proteins were calgranulin A(SA1008), lipocalin-1(LCN1), lysozyme C(LYZ), mammaglobin-B(SCGB2A1), proline-rich protein 4(PRR4), transferrin(TF), and calgranulinB(S100A9). The top 10 hub genes were serum albumin(ALB), tumor necrosis factor(TNF), interleukin 6(IL6), IL1B, IL8, matrix metalloproteinase 9(MMP9), alpha-1-antitrypsin(SERPINA1), IL10, complement component 3(C3), and lactotransferrin(LTF). Module analysis suggested MMP9 and PRR4 as seed genes. KEGG analysis showed that differential proteins were mainly enriched in the IL17 signaling pathway(61.9%).CONCLUSION: The results reveal potential molecular targets and pathways for DE and confirm the association between the pathogenesis of DE and inflammation. Further in-depth research is needed to confirm the significance of these biomarkers in clinical practice.

OBJECTIVE: To explore the function of LIM and calponin homology domains 1 (LIMCH1) in the development and progression of oral squamous cell carcinoma (OSCC), along with their potential clinical applications. METHODS: By utilizing transcriptome sequencing data from two groups of oral squamous cell carcinoma patients, along with bioinformatics analytical techniques such as Gene Ontology (GO) and gene co-expression networks, we identified genes that might play a pivotal role in the pathogenesis of oral squamous cell carcinoma. We employed real-time quantitative PCR and Western blotting to validate the expression patterns of these genes across twelve patient tissue samples. Furthermore, we conducted CCK-8 assays, flow cytometry analyses, and scratch wound healing assays to assess the impact of key genes on the biological behaviors of both the Cal27 oral squamous cell carcinoma cell line and the potentially malignant DOK oral lesion cell line. Additionally, we examined correlations between these key genes and clinical disease parameters in 214 oral squamous cell carcinoma patients using The Cancer Genome Atlas (TCGA) data; gene set enrichment analysis (GSEA) analysis results were also incorporated to enhance our findings from real-time quantitative PCR and Western blotting regarding potential mechanisms underlying the action of these key genes. RESULTS: The integrated analysis of sequencing data and bioinformatics revealed that LIMCH1 exhibited significantly reduced mRNA (P < 0.001) and protein levels (P < 0.01) in the oral squamous cell carcinoma tissues compared with normal control tissues. In the Cal27 cells, the low LIMCH1 level group demonstrated a larger wound healing area within 24 hours than the control group (P < 0.01), enhanced proliferation capacity over 72 hours relative to the control group (P < 0.01), and an increased apoptosis rate within 24 hours compared with the high expression group (P < 0.05). However, no significant differences were observed between the low and high level groups in DOK cells. Furthermore, it was determined that low LIMCH1 level correlated with poor prognosis in the patients (P=0.013) and a higher lymph node metastasis rate (P < 0.05). Investigations into the potential mechanisms of action indicated that LIMCH1 did not influence the onset or progression of oral squamous cell carcinoma via the epithelial-mesenchymal transition pathway. CONCLUSION LIMCH1 level may function as a promising biomarker to aid in the prognostic assessment of oral squamous cell carcinoma; however, its precise mechanistic role requires further investigation.
Humans ; Mouth Neoplasms/metabolism* ; Prognosis ; Carcinoma, Squamous Cell/metabolism* ; Biomarkers, Tumor/metabolism* ; LIM Domain Proteins/metabolism* ; Cell Line, Tumor ; Cell Proliferation ; Male ; Female

OBJECTIVES: To develop an early atrial fibrillation (AF) risk prediction model based on large-scale electrocardiogram (ECG) data from the Chinese population. METHODS: The data of multiple ECG records of 30 383 patients admitted in the Chinese PLA General Hospital between 2009 and 2023 were randomly divided into the training set and the internal testing set in a 7:3 ratio. The predictive factors were selected based on the training set using univariate analysis, LASSO regression, and the Boruta algorithm. Cox proportional hazards regression was used to establish the ECG model and the composite model incorporating age, gender, and ECG model score. The discrimination power, calibration, and clinical net benefits of the models were evaluated using the area under the receiver operating characteristic curve (AUROC), calibration curves, and decision curves. RESULTS: The cohort included 51.1% male patients with a median age of the patients of 51 (36, 62) years and an AF incidence of 4.5% (1370/30 383). In the ECG model, the parameters related to the P wave and QRS complex were identified as significant predictors. In the testing set, the AUROC of the ECG model for predicting 5-year AF risk was 0.77 (95% CI: 0.74-0.80), which was increased to 0.81 (95% CI: 0.78-0.83) after incorporating age and gender, with a net reclassification improvement of 0.123 and an integrated discrimination improvement of 0.04 (P<0.05). The calibration curve of the model was close to the diagonal line. Decision curve analysis showed that the clinical net benefit of the composite model was higher than that of the ECG model across the majority of threshold probability. CONCLUSIONS The composite model incorporating quantitative ECG features during sinus rhythm, along with age and gender, can effectively predict AF risk in the Chinese population, thus providing a low-cost screening tool for early AF risk assessment and management.
Humans ; Atrial Fibrillation/epidemiology* ; Electrocardiography ; Middle Aged ; Male ; Female ; China/epidemiology* ; Proportional Hazards Models ; Adult ; Risk Factors ; Risk Assessment ; East Asian People

Objective To explore the predictive value of serum homo sapiens microRNA(hsa-miR)-30c-5p expression in patients with type 2 diabetes mellitus(T2DM)for microvascular complications.Methods A total of 205 T2DM patients admitted to Bazhong Central Hospital from May 2021 to September 2022 were selected as the diabetes group,and the diabetes group was further divided into diabetes with combined group(n=124)and non combined group(n=81)according to the microvascular complications of the patients.In addition,205 healthy people who underwent physical examination during the same period were selected as the control group.The expression of hsa-miR-30c-5p in serum was detected by reverse transcription-polymerase chain reaction(RT-PCR)and compared.The factors affecting microvascular complications were analyzed using multivariate logistic regression analysis,and receiver operating characteristic(ROC)curves were plotted to predict the value of serum hsa-miR-30c-5p expression in predicting microvascular complications in T2DM patients.Results The expression of serum hsa-miR-30c-5p in the combined group(0.58±0.06)and the non-combined group(0.72±0.08)were lower than that in the control group(0.89±0.21),and the differences were significant(t=16.038,7.079,all P=0.001).The combined group was lower than the non-combined group,and the difference was significant(t=14.289,P=0.001).The course of diabetes[(OR(95％CI):3.873(2.976～4.770)],uric acid[(OR(95％CI):2.125(1.211～3.040)]and glycosylated hemoglobin[(OR(95％CI):2.680(1.745～3.616)]were independent risk factors for microvascular complications in T2DM patients(all P＜0.05),while the time within the target range of glucose[(OR(95％CI):0.491(0.135～0.846)]and serum hsa-miR-30c-5p[(OR(95％CI):0.532(2.976～4.770)]were protective factors for microvascular complications in T2DM patients(all P＜0.05).The sensitivity,specificity and area under the curve(95％CI)of serum hsa-mir-30c-5p expression in predicting microvascular complications in T2DM patients were 81.45％,85.19％and 0.802(0.741～0.854),respectively.Conclusion The expression of serum hsa-miR-30c-5p in patients with T2DM is abnormally reduced,and serum hsa-miR-30c-5p is a protective factor for microvascular complications in patients with T2DM.It may have a certain predictive value for microvascular complications in patients with T2DM.

Guillain-Barre syndrome rarely develops after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and only a few reports exist in China. Guillain-Barre syndrome is an acute and life-threatening condition that requires early diagnosis and treatment. A patient with acute myeloid leukemia underwent allogeneic HSCT for >5 months and gradually developed limb muscle weakness and limited eye movement after coexisting with delayed acute intestinal graft-versus-host disease. After the examination of cerebrospinal fluid and electromyography, the diagnosis of Guillain–Barre syndrome was confirmed. After a high-dose intravenous immunoglobulin (IVIg) treatment, muscle strength gradually recovered, and the prognosis was good.

The onset of myasthenia gravis (MG) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) seriously threatens the survival of patients, since it is acute, and is prone to rapid progression. Two patients with acute myeloid leukemia (AML), who had undergone allo-HSCT developed shortness of breath, and gradually developed cervical weakness and dyspnea. The acetylcholine receptor (AChR) antibody and neostigmine test enabled the diagnosis of MG. The condition of the patients improved after treatment with pyridostigmine bromide, glucocorticoids and rituximab.

OBJECTIVE To confirm the therapeutic effect of Jintiange capsules on osteoarthritis(OA) and the potential mechanism of synovial mesenchymal stem cell exosomes(SMSC-Exos) and articular chondrocytes(ACs) in the treatment of OA based on high-throughput sequencing technology. METHODS Type Ⅱ collagenase-induced OA rats were used for efficacy verification through general behavioral observation, bipedal balance difference experiment, mechanical foot reflex threshold, Micro-CT observation, and Safranin O-Fast Green staining. SMSCs and ACs were cultured in suitable concentration of drug-containing serum, and mRNA sequencing was performed on ACs in the control, model, and Jintiange capsules groups, as well as miRNA sequencing on SMSC-Exos. Differential expressed mRNAs and miRNAs were screened and target genes were predicted. The common differential expressed genes between SMSC and ACs were obtained by intersecting the differential expressed genes, and a miRNA-mRNA regulatory network was constructed using Cytoscape software. The expression trend analysis of common differential expressed genes was conducted, as well as the correlation analysis between differential expressed gene mRNA and miRNA, Micro-CT efficacy indicators, and differential expressed gene mRNA. RESULTS Under the pathological state of OA, the expression of miRNA-23a-3p, miRNA-342-3p, miRNA-146b-5p, miRNA-501-3p, and miRNA-214-3p were down-regulated, while miRNA-222-3p, miRNA-30e-3p, miRNA-676-3p, and miRNA-192-5p were up-regulated (P<0.05). The expressions of these miRNAs were significantly reversed after intervention with drug-containing serum of Jintiange capsules. There was a certain correlation between Micro-CT efficacy indicators, mRNA and miRNA. CONCLUSION Jintiange capsule has obvious efficacy in the treatment of OA, and its mechanism may be related to the promotion of SMSC-Exos targeting ACs to transport miRNA and then regulate Serpinb10, Ntn1, Il1b, Tgm2, Megf10, Il11, Cd40, Slc15a3, Pou2f2 and other genes.

OBJECTIVE To investigate the effects of sacubitril/valsartan on renal function in patients with primary hypertension. METHODS A retrospective study was conducted among patients with primary hypertension who were admitted to PLA Strategic Support Force Characteristic Medical Center from January 2018 to June 2023. Based on their medication， they were divided into two groups： sacubitril/valsartan group and valsartan group. Propensity score matching was used to match baseline data between the two groups. Patients were treated with antihypertensive drugs based on improving their lifestyle. Sacubitril/valsartan group additionally received oral administration of 200 mg Sacubitril/valsartan tablets once daily， while valsartan group additionally received oral administration of 80 mg Valsartan capsules once daily. The increase amplitude of serum creatinine from baseline， the proportion of patients with elevated serum creatinine ＞30%-50% or ＞50%， and the proportion of patients with hyperkalemia （serum potassium ≥5.5 mmol/L） were compared between two groups at 2 months and 6 months after treatment. The trends of changes in serum creatinine， serum potassium and estimated glomerular filtration rate （eGFR） were compared between the two groups before treatment （at baseline）， 2 months and 6 months after treatment. RESULTS After propensity score matching， there were 62 patients in sacubitril/valsartan group and 61 patients in valsartan group； there were no significant differences in baseline characteristics between the two groups before treatment （P＞0.05）， indicating comparability. After 6 months of treatment， the increase of serum creatinine in the sacubitril/valsartan group was significantly lower than that in the valsartan group （P＝0.003）； the proportion of patients with elevated serum creatinine ＞30%-50% in the sacubitril/valsartan group was significantly lower than that in the valsartan group （P＝0.045）. None of the patients experienced hyperkalemia events after 2 months and 6 months of treatment. Repeated measures analysis of variance showed significantly statistical differences in serum creatinine and eGFR between the two groups within 6 months of treatment （P＜0.001）. Patients taking valsartan experienced a continuous increase in serum creatinine levels and a decrease in eGFR， while patients taking sacubitril/valsartan showed a first increase and then a decrease in serum creatinine levels， and a first decrease and then an increase in eGFR with a prolonged duration of medication. CONCLUSIONS Sacubitril/valsartan can delay or even reverse the decline in renal function levels， and limit the deterioration of renal function in patients with primary hypertension， without increasing the risk of hyperkalemia.

Objective:To investigate the clinical efficacy of three-connections and four-screwings technique in the treatment of high double column acetabular fractures through a single ilioinguinal approach.Methods:A retrospective study was conducted to analyze the data of 42 patients who had been treated for high double column acetabular fractures from June 2017 to June 2020 at Trauma Ward 2, Department of Orthopedics and Traumatology, The First Hospital of Traditional Chinese Medicine of Changde. There were 19 males and 23 females with an age of (42.7±25.6) years. 29 injuries were due to a traffic accident, 12 ones to fall from a height, and one to fall. The time from injury to operation was (4.5±2.1) days. All the patients were treated by the three-connections and four-screwings technique through a single ilioinguinal approach. Briefly, the anterior column was connected and secured to the main bone using 3 routes, and the posterior column was attached and fixated to the anterior column reset using 2 or 3 of the 4 screwings. The operation time, intraoperative blood loss, fracture reduction quality, fracture healing time, hip function at the last follow-up and complications during the follow-up were recorded.Results:For this cohort, the operation time was (150.0±30.5) min, and intraoperative blood loss (300.0±50.0) mL. According to the Matta scale for postoperative acetabular fracture reduction, 34 cases were excellent, 6 cases good, and 2 cases acceptable, with an excellent and good rate of 95.2% (40/42). After operation one patient had fat liquefaction and wound exudation which responded to drainage and dressing change. The 42 patients were followed up for (15.0±3.4) months. All fractures healed after (11.0±2.0) months. By the modified Merle d'Aubigné & Postel scoring system, the hip function was evaluated at the last follow-up as excellent in 33 cases, as good in 6 cases, and as fair in 3 cases, yielding an excellent and good rate of 92.9% (39/42).Conclusions:In the treatment of high double column acetabular fractures, the three-connections and four-screwings technique through a single ilioinguinal approach can lead to fine reduction and rigid fixation by lag screw compression and neutralization plate protection. Consequently, early functional exercises can be performed to secure good therapeutic outcomes for the patients.