ObjectiveTo investigate the effect and mechanism of Qingre Sanzhuo decoction in treating gouty arthritis （GA） combined with hyperuricaemia （HUA）. MethodsSixty male SD rats were randomized into normal， model， colchicine （0.5 mg·kg^-1）， and low-， medium-， and high-dose （17， 34， 68 g·kg^-1， respectively） Qingre Sanzhuo decoction groups （n=10）. The rats in other groups except the normal group were treated with the modified method for the modeling of GA combined with HUA. The drug intervention groups were administrated with corresponding drugs by gavage in the afternoon every day and the normal group and the model group were administrated with an equal volume of sterile normal saline by gavage. The level of uric acid （SUA） in the serum was measured 2 h after the last administration. The degree of ankle joint swelling was calculated 0.5， 12， 24， 48 h after modeling， and joint inflammation was scored. The pathological changes of ankle joints were observed by hematoxylin-eosin staining， and the serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， C reactive protein （CRP）， and interleukin-18 （IL-18） were measured by enzyme-linked immunosorbent assay. Real-time PCR was performed to determine the mRNA levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing CARD （ASC）， cysteinyl aspartate-specific protease-1 （Caspase-1）， gasdermin D （GSDMD）， and nuclear factor-kappa B （NF-κB） in the synovial tissue of ankle joints. Western blot was employed to determine the protein levels of NLRP3， ASC， and Caspase-1 in ankle joints. The immunohistochemical method was used to detect the expression of GSDMD and NF-κB in the synovial tissue of ankle joints. ResultsCompared with the normal group， the model group showed increased SUA in the serum （P<0.05）， ankle joint swelling and joint inflammation （P<0.05）， increased number of blood vessels in the synovium， inflammatory cell foci in the synovial bursa， elevated serum levels of TNF-α， IL-1β， CRP， and IL-18 （P<0.05）， and up-regulated mRNA and protein levels of NLRP3， ASC， Caspase-1， GSDMD， and NF-κB in the synovial tissue of ankle joints （P<0.05）. Compared with the model group， the medium- and high-dose Qingre Sanzhuo decoction groups showed reduced SUA in the serum （P<0.05）， alleviated ankle joint swelling and joint inflammation （P<0.05）， lowered serum levels of TNF-α， IL-1β， CRP， and IL-18 （P<0.05）， and down-regulated mRNA and protein levels of NLRP3， ASC， Caspase-1， GSDMD， and NF-κB in the synovial tissue of ankle joints （P<0.05）. However， in terms of ameliorating the pathological changes of ankle joints， only the high-dose Qingre Sanzhuo decoction group showed normal morphology of the synovial membrane of ankle joints and no obvious lesion in the articular cartilage. ConclusionQingre Sanzhuo decoction may play a role in preventing and controlling GA combined with HUA by down-regulating the activity of NLRP3/ASC/Caspase-1 pathway and inhibiting the expression of inflammatory cytokines， such as TNF-α， IL-1β， CRP， and IL-18.

Alcohol exposure, as a widespread environmental factor, is highly toxic and teratogenic. Embryonic stem cells (ESCs) are pluripotent and key to development, and their gene expression is tightly regulated, allowing the cells to differentiate without self-renewal. Numerous studies showed that alcohol is an important factor affecting the differentiation of ESCs. In this paper, we systematically summarized four major molecular mechanisms underlying alcohol associated differentiation of ESCs: (1) inhibition of the Wnt signaling pathway; (2) restriction of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway; (3) alteration of the expression of pluripotent transcription factors; and (4) activation of the nuclear transcriptional program. Through the above mechanisms, alcohol induces aberrant expression of differentiation-related genes and alters the direction of cellular differentiation towards specific lineages, thereby affecting normal embryonic development. Based on the studies on ESCs modeling and other in vitro and in vivo differentiation experiments, the molecular basis of how alcohol affects differentiation by interfering with signaling networks and transcriptional regulation was elucidated, and the results of current research in this field were also summarized, which is crucial for understanding alcohol-mediated toxic effects.

PURPOSE: To investigate the regulatory role of nerve injury-induced protein 1 (NINJ1) in the anti-inflammatory function of human umbilical cord mesenchymal stem cells (hUC-MSCs) co-stimulated by interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). METHODS: hUC-MSCs were expanded in vitro using standard protocols, with stem cell characteristics confirmed by flow cytometry and multilineage differentiation assays. The immunomodulatory properties and cellular activity of cytokine-co-pretreated hUC-MSCs were systematically evaluated via quantitative reverse transcription RT-qPCR, lymphocyte proliferation suppression assays, and Cell Counting Kit-8 viability tests. Transcriptome sequencing, Western blotting and small interfering RNA interference were integrated to analyze the regulatory mechanisms of NINJ1 expression. Functional roles of NINJ1 in pretreated hUC-MSCs were elucidated through gene silencing combined with lactate dehydrogenase release assays, Annexin V/Propidium Iodide apoptosis analysis, macrophage co-culture models, and cytokine Enzyme-Linked Immunosorbent Assay. Therapeutic efficacy was validated in a cecal ligation and puncture-induced septic mouse model: 80 mice were randomly allocated into 4 experimental groups (n=20/group): sham group (laparotomy without cecal ligation); phosphate-buffered saline-treated group (cecal ligation and puncture (CLP) + 0.1 mL phosphate-buffered saline); hUC-MSCs (small interfering RNA (siRNA)-interferon-gamma and tumor necrosis factor-alpha co-stimulation (IT))-treated group (CLP + hUC-MSCs transfected with scrambled siRNA); and hUC-MSCs (siNINJ1-IT)-treated group (CLP + hUC-MSCs with NINJ1-targeting siRNA). RESULTS: hUC-MSCs demonstrated compliance with International Society for Cellular Therapy criteria, confirming their stem cell identity. IFN-γ/TNF-α co-pretreatment enhanced the immunosuppressive capacity of hUC-MSCs, accompanied by the reduction of cellular viability, while concurrently upregulating pro-inflammatory cytokines such as interleukin-6 and interleukin-1β. This co-stimulation significantly elevated NINJ1 expression in hUC-MSCs, whereas genetic silencing of NINJ1 effectively suppressed pro-inflammatory cytokine production and attenuated damage-associated molecular patterns release through inhibition of programmed plasma membrane rupture. Furthermore, the NINJ1 interference potentiated the ability of cytokine-pretreated hUC-MSCs to suppress LPS-induced pro-inflammatory responses in RAW264.7 macrophages. In cecal ligation and puncture-induced sepsis model, NINJ1-silenced hUC-MSCs exhibited enhanced therapeutic efficacy, manifested by reduced systemic inflammation and multi-organ damage. CONCLUSION Our findings shed new light on the immunomodulatory functions of cytokine-primed MSCs, offering groundbreaking insights for developing MSC-based therapies against inflammatory diseases via interfering the expression of NINJ1.
Mesenchymal Stem Cells/drug effects* ; Animals ; Interferon-gamma/pharmacology* ; Tumor Necrosis Factor-alpha/pharmacology* ; Humans ; Mice ; Umbilical Cord/cytology* ; Cells, Cultured ; Apoptosis ; Male

Osteosarcoma is a common primary malignant bone tumor with highly aggressive and distal metastasis and poor prognosis. Abnormal metabolism of iron, an essential nutrient with electron-exchange capacity and an important participant in cellular activities, is closely associated with the progression of osteosarcoma. Ferroptosis has been shown to regulate osteosarcoma progression and play an important role in the treatment of osteosarcoma. Exploring the application of relevant molecular mechanisms of ferroptosis in osteosarcoma and the current status of pharmacological intervention may provide new strategies for the treatment of osteosarcoma.

Humans ; Albumins ; Albuminuria/urine* ; Blood Pressure ; China/epidemiology* ; Creatinine ; Risk Factors ; Aged

Objective:To investigate the role of subcutaneous negative pressure drainage device in the prevention of surgical site infections (SSI) of superficial incisional in lower digestive tract open surgeries.Methods:Clinical data of 104 patients receiving open surgeries on lower digestive tract at Beijing Friendship Hospital, Capital Medical University from October 2018 to June 2020 was analyzed by a propensity score matching (PSM), and the clinical data of 104 patients receiving open surgeries on lower digestive tract at Beijing Friendship Hospital, Capital Medical University from February to December 2021 was analyzed by a randomized controlled trial (RCT). Chi-square tests were conducted to analyze the association of subcutaneous negative pressure drainage device with SSI of superficial incisional. Univariate and multivariate Logistic regression analysis were used to identify the risk factors for SSI in superficial incisions.Results:Patients with subcutaneous negative pressure drainage device encounter significantly less SSI of superficial incisional in both the PSM study ( P=0.007) and the RCT study ( P=0.049). In the PSM study, the independent risk factors for SSI of superficial incisional via univariate and multivariate Logistic regression analysis were absence of subcutaneous drainage ( Puni=0.012, Pmulti=0.009) and postoperative anastomosis leak ( Puni=0.054, Pmulti=0.034). In the RCT study, the independent risk factors for SSI of superficial incisional via univariate and multivariate Logistic regression analysis were absence of subcutaneous drainage ( Puni=0.061, Pmulti=0.017), eldly ( Puni=0.076, Pmulti=0.032), long incision ( Puni=0.078, Pmulti=0.040). Conclusion:Subcutaneous negative pressure drainage device can significantly reduce SSI of superficial incisional in lower digestive tract open surgeries.

Periostin is a highly conserved functional protein, which plays an important role in the process of vascular injury and myocardial fibrosis. In recent years, there have been more and more studies on the peirostin protein in cardiovascular diseases. This article summarizes the present understanding regarding the relationship between periostin and cardiovascular disease.

Objective: To investigate the diagnosis and treatment of synchronous double primary malignant tumours of the tongue and lung. Methods: A case of adenoid cystic carcinoma（ACC） and lung adenocarcinoma with double primary malignancy was retrospectively analyzed. Results: The tumor of patient′s tongue base gradually grew. MRI showed multiple enlarged lymph nodes on both sides of neck. CT of the chest showed obvious lesions in the anterior basal segment of the right lower lobe. The pathological biopsy of the tongue mass identified ACC, and pathological biopsy of the lung mass identified lung adenocarcinoma. The tongue and lung tumors were both surgically resected, and the tongue defect was repaired at the same time. No residue was found after surgery, and no recurrence was found during the follow-up period. The aesthetic and functional restoration of the lingual region was good. Conclusion There are few cases of adenoid cystic carcinoma and lung adenocarcinoma with double primary malignancies, and the related diagnosis and treatment are very difficult; the simultaneous removal of double primary malignant tumors may achieve good prognosis.

Objective A prospective cohort study was carried out to assess the mortality and potential risk factors for primary liver cancer (PLC) in Haimen city of Jiangsu province.Methods The cohort involved 89 789 adult residents aged 25-69 years.Upon the entry of this project,each subject was asked to complete a questionnaire and to provide a blood sample of 10 ml.Surface antigen of hepatitis B virus (HBsAg) was tested by radioimmunoassay.All the subjects were followed-up every year for vital statistics and death certificate information until 2014.Cox proportional hazard model was used to estimate the hazard ratio (HR) and 95％ confidence interval (95％ CI) for PLC mortality associated with HBsAg status and other risk factors.Results During the 1 299 611 person-years of follow-up,a total of 2 583 PLC cases were identified,including 2 149 men and 434 women.Mortality of the PLC for men and women were 247.80/100 000 person-years and 100.38/100000 person-years,respectively.Among those who died of PLC,73.87％ had been tested HBsAg positive.HBV infection seemed the predominant risk factor for PLC and the HRs were 15.97 for men (95％CI:14.29-17.85) and 21.63 for women (95％CI:16.16-28.96) respectively.Ageing,cigarette smoking,previous history of hepatitis,and family history of HCC were factors associated with the increased risk for PLC.Conclusion People living in Haimen city had a high risk on PLC.HBV infection appeared the most important risk factor for HCC mortality in this area.

Objective To explore the relations of the doctor-patient relationship to psychological security and stress.Methods Totally 430 operation patients were selected and followed-up.A survey was performed using the Security Questionnaire (SQ),the Patient Doctor Relationship Questionnaire 13-Item Version (PDRQ-13),the Hospital Stress Rating Scale (HSRS) Results The average score of SQ was lower than medium value in operation patients.The SQ scores of operation patients with emergency operation were 39.50±10.51,lower than those of selective operation which were 49.02±10.37 and limited operation which were 47.67±10.29 (P ＜ 0.05).The SQ scores of operation patients who didn't provided themselves were 37.33±10.10,lower than those of basically which were 40.10±10.83 and partly provided for themselves which were 43.50±10.51 (P＜ 0.05).The SQ scores of operation patients in severe group according severity of illness were 37.13±10.40,lower than those of them in mild group which were 39.19±10.24 and moderate group which were 41.38±10.01 (P＜ 0.01).The SQ scores of post-operation patients were 44.32±9.96,higher than post-operation patients which were 40.36±10.81 (P ＜ 0.01).The lack of comforts (LC),lack of information (LI) and risks of serious disease (RSD) scores of post-operation patients were 49.23±30.62,30.46±21.42,52.84±31.22,lower than those of post-operation patients which were 52.37±32.06,35.25±20.14,80.12±33.18 (P ＜ 0.05).The path analysis showed that the regression relationship between SQ scores and PDRQ scores,RSD scores was established (β=0.40,-0.26,P ＜ 0.01),and the PDRQ-13 scores was a mediator between the scores of LC,LI,RSD and the SQ scores (β=0.40,P＜0.01).The PDRQ-13 scores was a adjustor between the RSD scores and the SQ scores (β=-0.34,P ＜ 0.01).Conclusions The operation patients have a low level of the sense of security which is statistically significant with surgical types,the ability to care for themselves and severity of illness.The sense of security of post-operation patients were higher than those of pre-operation patients.The recognition of physician-patient relationship may be play a mediating and adjusting role between the sense of security and stress.The surgical stress affect patient security and physician-patient relationship.